Tissue-catalyzed growth of polymers as epithelial therapeutics

Abstract

The present disclosure provides compositions, methods and kits that can make polymers grow in situ on or within a subject. In some aspects, monomeric dopamine is polymerized in vivo to form polymers on tissues. In additional aspects, compositions, methods and kits can be used to treat or prevent diseases or disorders.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application USSN 62 / 947,582 filed on December 13, 2019, U.S. Provisional Patent Application USSN 63 / 050,206 filed on July 10, 2020, and U.S. Provisional Patent Application USSN 63 / 050,216 filed on July 10, 2020, the contents of each of which are incorporated herein by reference in their entirety.

[0003] Government support

[0004] This invention was made with government support under Grant No. R01 EB000244 awarded by the National Institutes of Health. The government has certain rights in this invention. Background Art

[0005] The small intestine is a multifunctional organ with multiple physiological functions. The epithelium covering the gastrointestinal tract is a multifunctional tissue that plays an important role as a permeable barrier for selective transport (such as absorption) and a protective armor against various pathogens. Specifically, the epithelial tissue of the gastrointestinal tract (especially the small intestinal epithelium) is not only a protective screen against physical wear, chemical stress and pathogens, but also a dynamic lining for signal sensing, molecular transport and immune coordination. Selective intervention of the small intestinal mucosa is related to disease treatment and health management. At the same time, in order to meet the challenge of specifically and effectively restoring or enhancing the function of the small intestinal epithelium, a variety of well-designed biotechnologies have been developed. These specific technologies using ingeniously designed tissue adhesives (e.g., pH-dependent polymers, metal complexes, and targeted nanoparticles) or systemically engineered tissue substitutes (e.g., epithelial grafts, autologous cell layers, and plastic epithelial sleeves) are effective tools that are beneficial to the restoration of epithelial dysfunction and the treatment of systemic diseases. 1-7 Despite these advances in research laboratories, widespread adoption of these technologies in medical laboratories and healthcare clinics has been limited, thus hindering their impact 8-10 This limited implementation is a result of multiple factors: invasive transplantation, potential immunogenicity, toxicity, and the imprecision, instability, and inconvenience of current tissue-targeting strategies, which restrict selective small-bowel access.

[0006] Similarly, the ability to intervene in the small intestine to treat digestive disorders and systemic diseases has sparked interest in developing a variety of targeted drugs. 31,32 However, challenges with small intestine-specific targeting have hampered widespread adoption 9,10Alternative techniques that require surgical transplantation, such as inguinal intussusception, are limited by therapies with complex procedures, low biocompatibility, inflammatory risks, and high costs. Therefore, developing the functionality of an epithelial layer through advanced biotechnologies while maintaining the physiological properties of the tissue remains a challenge. Summary of the invention

[0007] Disclosed herein are compositions, methods and kits for forming polymers in situ in a subject. The disclosure enables polymers to grow on the surface of epithelial tissues, thereby providing a transient coating with adjustable functions. Polymer coatings rely on dopamine polymerization catalyzed by endogenous cell enzymes (catalase), strong tissue adhesion generated by chemical cross-linking, and functional agents optionally introduced by facile conjugation. For example, catalase in epithelial tissues in gastrointestinal epithelium catalyzes polydopamine growth on the small intestinal mucosa. In addition, catalase expression levels along tissues (such as the gastrointestinal tract) allow effective and specific formation of polymer coatings.

[0008] The disclosed compositions, methods and kits can be used, for example, to enhance lactose digestion by immobilizing β-galactosidase in the intestine, resulting in improved lactose digestion; to regulate nutrient intake by hindering glucose absorption; and to control drug delivery by prolonging the residence time of active pharmaceutical ingredients in specific anatomical locations.

[0009] In one aspect, provided herein is a method of forming a polymer in situ in a subject, the method comprising administering to the subject a composition comprising a monomer and an oxygen source, wherein the monomer and the oxygen source contact a catalyst endogenous to the subject and the catalyst polymerizes the monomer, wherein the monomer is dopamine or a salt thereof, the oxygen source is hydrogen peroxide or urea hydrogen peroxide, and the endogenous catalyst is selected from catalase or peroxidase.

[0010] In one aspect, the present disclosure provides a composition comprising dopamine, an oxygen source, and optionally a buffer. In some aspects, the composition further comprises a digestive enzyme, a nutrient blocker, a nutritional formulation, a radioprotectant, an active pharmaceutical ingredient, a diagnostic agent, or a combination thereof.

[0011] In another aspect, the present disclosure provides a method of treating a disease or disorder, the method comprising administering to a subject in need thereof an effective amount of a composition as described herein.

[0012] In one aspect, the present disclosure provides a method of preventing a disease or disorder, the method comprising administering to a subject in need thereof an effective amount of a composition as described herein.

[0013] In another aspect, the present disclosure also provides a kit comprising a composition as described herein and instructions for administering the composition.

[0014] The details of certain embodiments of the present disclosure are set forth in the following Detailed Description of Certain Embodiments. Other features, objects and advantages of the present disclosure will be apparent from the definitions, examples and claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 A-1H. Endogenous enzyme-catalyzed polydopamine growth on the intestinal epithelium. Figure 1 A shows a schematic diagram of tissue accelerated polymerization of the disclosed technology. Dopamine monomers in the oral monomer solution are rapidly oxidized under the catalysis of endogenous catalase in the presence of hydrogen peroxide (H2O2) and form a polydopamine coating on the small intestinal epithelium. Due to the uneven distribution of catalase along the digestive tract, this specific small intestinal coating and targeting is achieved. Figure 1 B shows a schematic diagram of catalase-accelerated polydopamine polymerization in a hypoxic environment. In an extremely hypoxic environment as depicted above the horizontal arrow, dopamine (colorless) oxidation (using oxygen as an oxidant) and polydopamine (dark brown) formation are inhibited and even nearly quenched in the presence of H2O2. In contrast, catalase can promote oxygen release (using H2O2 as an oxygen source) and accelerate polydopamine polymerization, for example, by about 400 times. Therefore, as shown below the horizontal arrow, colorless dopamine rapidly polymerizes into polydopamine in the presence of hydrogen peroxide and catalase. TAPPE = Tissue-accelerated polymerization on the external epithelium. Figure 1 C shows the Figure 1 B Visual observation of polydopamine polymerization at different time points under the conditions shown. Figure 1 D shows Figure 1 Extinction of the samples shown in C was measured at 700 nm. The optical extinction produced in 20 seconds under catalase catalysis was the same as the extinction produced in 2 hours under other conditions. Figure 1 E depicts an image showing polydopamine coating on the mucosal and serosal sides of porcine small intestine after application of the ex vivo coating treatment as disclosed herein, wherein the scale bar indicates 2 cm. Figure 1 F shows quantitative evaluation of in situ ex vivo polymerization kinetics. The polydopamine signal reached completion within 12 min. Data are reported as mean ± SD of three porcine tissue samples. Figure 1 G depicts images showing porcine tissue samples in different parts of the gastrointestinal tract before and after tissue accelerated polymerization coating. Samples (6 mm in diameter) were collected at three random sites on the polydopamine coated tissue. Figure 1 H shows Figure 1Quantitative measurement of polydopamine signal intensity for samples shown in G. The intensity difference between small intestine and other tissues is statistically significant. ****P<0.05, one-way analysis of variance (ANOVA) with post hoc Bonferroni. Data are reported as mean±SD of three different tissue samples.

[0016] Figure 2 A-2H. Biological mechanisms of accelerated tissue aggregation. Figure 2 A shows the evaluation of the relationship between tissue catalytic capacity and polydopamine polymerization. Porcine tissue lysates were added individually to tissue accelerated polymerization solutions, and the extinction of each solution was measured at 700 nm. Both visual assessment (upper panel) and quantitative measurements (lower panel) of polydopamine solutions showed differences in catalytic capacity when comparing small intestinal epithelium to other tissues and controls (no lysates). *P < 0.05, one-way ANOVA and post hoc Bonferroni. Data are reported as mean ± SD of three replicates. Figure 2 B-2C shows that by using a specific inhibitor of catalase ( Figure 2 B) or antibodies that induce immunoprecipitation ( Figure 2 C) Treat the lysate to verify the presence of catalase Figure 2 Unique effects in the reactions shown in A. The difference in relative catalytic capacity between treated and untreated groups was visually and statistically significant. ***P<0.001 (by two-tailed t-test). Data are reported as mean±SD of three different tissue samples. Figure 2 D-2F shows the results of catalase activity assay ( Figure 2 D) Real-time PCR ( Figure 2 E) and Western blot ( Figure 2 F) to quantify catalase expression (gene and protein levels) along the porcine gastrointestinal tract. Figure 2 Similar distribution characteristics were achieved in D-2F, indicating higher expression levels of catalase in the small intestinal epithelium compared to other tissues. The difference is statistically significant. ***P < 0.05, one-way ANOVA and post hoc Bonferroni. Data are reported as mean ± SD of three replicates. Figure 2 G shows microscopic analysis of polydopamine-coated small intestinal epithelium, showing a thin polydopamine layer (indicated by arrows) coating the outer villi, but not on control tissue (no coating). Scale bar, 150 μm. Figure 2 H shows bright field imaging of uncoated tissue sections treated with specific peroxisome / catalase staining (left) and tissue-accelerating polymerization solution (right). Dark brown polydopamine spots were observed within the villus tips, and the staining pattern was consistent with conventional peroxisome / catalase staining. Scale bar, 150 μm.

[0017] Figure 3 A-3I. In vivo performance of tissue accelerated polymerisation coatings in pigs. Figure 3 A-3C shows a schematic diagram and photograph of in vivo gastrointestinal endoscopic real-time recording of polydopamine formation during the tissue accelerated polymerization process. Under endoscopic visual guidance, the tissue accelerated polymerization solution was directly administered to the pig small intestine through a catheter, and an endoscopic camera was placed inside and outside the solution in the small intestine for observation. Figure 3 B-3C shows endoscopic images revealing the steps during polydopamine coating (bottom three panels). Oxygen bubbles are generated at the epithelium-solution interface (indicated by white arrows). Figure 3 D shows a schematic diagram of small bowel ligation (upper panel) and direct polydopamine coating assessment (lower panel). The tissue accelerated polymerization solution filled the intestinal lumen up to the clamp site and could not pass down to the lower small intestine. The isolated tissue showed different polydopamine coating before and after the clamp site. Figure 3 E shows a schematic diagram of polydopamine coated intestinal retention indicated by X-ray imaging of the polydopamine probe. X-ray images were taken for two tests: (I) short-term stability evaluation (rinsing coated area) and (II) long-term retention assessment (liquid diet for 24 hours). PDA = polydopamine. Figure 3 F shows an X-ray image of a polydopamine probe and polydopamine coating stably residing in the small intestine before and after flushing the imaging area, as shown in test (I). The stomach and small intestine (SI) regions are separated by white dashed lines. The polydopamine coating is indicated by a yellow arrow. Figure 3 G shows an X-ray image of polydopamine coated intestinal retention for the duration of test (II). The conventional probe was barely detectable after food exposure. Figure 3 H shows Figure 3 Quantitative signal intensity analysis of the coated small intestine region, i.e., the region of interest (ROI) in F. The enhancement and stability of the signal (before and after washing) of the polydopamine probe relative to the conventional (CON) probe indicates efficient probe introduction and stable polydopamine coating. Data are reported as mean ± SD of three different measurements. Figure 3 I shows Figure 3 Quantitative signal intensity analysis of polydopamine coating over time in G. From 2 to 6 hours, there was only a 28% difference in signal intensity, indicating prolonged retention of polydopamine coating. Data are reported as mean ± SD of three different measurements.

[0018] Figure 4 A-4G. Therapeutic applications enabled by accelerated tissue polymerization. Figure 4 A shows a schematic diagram of the tissue-accelerating polymerization therapeutic platform. Functional agents, including digestive enzymes, nutrient blockers, and anthelmintics, are introduced into the platform by oral administration to pigs along with the tissue-accelerating polymerization solution. Figure 4 B shows a schematic diagram of the introduction of digestive enzymes (β-galactosidase, β-gal) into the polydopamine coating on porcine intestinal epithelium to enhance the digestion of a substrate (lactose). After coating in vivo, the β-gal activity of the coated epithelium was evaluated. Figure 4 C shows a quantitative comparison of β-gal activity, showing increased enzyme activity in β-gal-coated tissues based on accelerated polymerization of tissues compared to negative controls. Data are reported as mean ± SD of four animals. Figure 4 D shows a schematic diagram of introducing a nano-crosslinker (blocker) into the tissue-accelerating polymerization coating to render the polydopamine coating impermeable, thereby preventing glucose uptake in the small intestine. After in vivo coating, oral glucose was administered to the pigs, and blood glucose concentrations were then monitored. Figure 4 E shows a quantitative comparison of blood glucose changes, showing a reduced blood glucose response in pigs with tissue accelerated polymerization coating relative to controls (no coating). Data were averaged (shown with black lines) between animals in each group (each animal is represented by a grey line). Figure 4 F shows a schematic diagram of coated drug (praziquantel) particles on intestinal epithelium for sustained release of therapeutic agent in the small intestine. Blood drug concentrations were analyzed over 48 hours after oral administration of praziquantel-tissue accelerated polymerization solution. Figure 4 G shows a quantitative comparison of pharmacokinetics, showing prolonged retention of praziquantel (with tissue-accelerated polymerization solution) relative to control (without tissue-accelerated polymerization solution). * indicates p < 0.02, two-sample t-test comparing praziquantel-tissue-accelerated polymerization and control groups at matched time points. Data are reported as mean ± SD of three animals.

[0019] Figure 5 A-5G. Compatibility of human tissue with accelerated tissue aggregation. Figure 5 A shows images of freshly excised tissue specimens from human small intestine before and after accelerated polymerization of ex vivo tissue. Dark brown polydopamine coating is clearly observed on the surface of human small intestine (lower image). Scale bar, 1 cm. Figure 5 B depicts coating kinetics showing ultrafast polydopamine signal onset in ex vivo human tissue. Polydopamine signaling reaches completion within 3 minutes. Figure 5 C shows the evaluation of tissue accelerated polymerization consistency. Tested tissue specimens from 3 donors of different ages, races and genders. Five in vitro evaluations were performed at random locations of the human small intestine. The quantitative measurement (right figure) of the polydopamine coating signal of the sample (6mm diameter) (left figure) before and after coating confirmed the consistent tissue accelerated polymerization coating performance. Data are reported with the mean ± SD of five parallel determinations. Figure 5D shows microscopic and histological analysis of frozen specimens (40 μm thick) and FFPE specimens (5 μm thick) collected from polydopamine-coated human small intestinal epithelium. A thin polydopamine layer was observed on the outer villi of the coated tissue. Uncoated tissue was used as a control. Histological studies (hematoxylin and eosin (H&E) staining) of adjacent frozen tissue sections and FFPE samples showed that the epithelial layer remained intact (wherein the staining pattern was similar to the control), indicating that there was no tissue toxicity. Scale bar, 150 μm. Figure 5 E depicts representative images showing no apparent reduction in polydopamine signal in coated human small intestine following mechanical agitation and scraping. Figure 5 F shows quantitative in vitro evaluation of polydopamine signal intensity in tissues coated under a range of physical conditions. The intensity differences between all conditions were not statistically significant (two-tailed t-test). Data are reported as mean ± SD of three replicates. Figure 5 G shows quantitative in vitro evaluation of polydopamine signal intensity in tissues coated under a range of chemical conditions. The intensity differences between all conditions were not statistically significant (two-tailed t-test). Data are reported as mean ± SD of three replicates.

[0020] Figure 6 A-6B. Comparison of polydopamine polymerization kinetics under different reaction conditions. Figure 6 A shows the extinction measured at 700 nm for samples undergoing polydopamine polymerization in air with and without H2O2 (control). Figure 6 B shows the extinction measured at 700 nm for samples (with and without H2O2 (control)) undergoing polydopamine polymerization under extremely low oxygen levels (hypoxic environment). Compared with conventional conditions (reaction without H2O2 in air), polydopamine polymerization (without H2O2) was inhibited by 65% ​​under extremely low oxygen levels. The addition of H2O2 almost quenched the polymerization of polydopamine in air and under hypoxic conditions.

[0021] Figure 7 A-7D. Fourier transform infrared (FTIR) spectra of dopamine, polydopamine standards and polymerization products. The dopamine prepared under conventional conditions ( Figure 7 A) and polydopamine ( Figure 7 B) and used as a standard. FTIR spectroscopy confirmed that catalase (commercially purified) catalyzed ( Figure 7 C) and catalase (from tissue lysate) catalyzed ( Figure 7 D) Polydopamine formation in the polymerization product. Indole (or dihydroindole) peaks (1515 and 1605 cm -1 ) and span 3200-3500cm -1The broad peak (hydroxyl structure) is almost identical to that in the polydopamine standard.

[0022] Figure 8 A-8C. Normalized extinction spectra of polydopamine standards and polymerization products. Polydopamine standards ( Figure 8 A), polymerization products catalyzed by catalase (commercially purified) ( Figure 8 B) and catalase (from tissue lysate) catalyzed polymerization products ( Figure 8 C) have almost the same UV-Vis spectra, confirming Figure 8 B and Figure 8 Polydopamine formation in C.

[0023] Fig. 9 .Tissue accelerated polymerization coating evaluation using porcine tissue specimens. The mucosa and serosa of the small intestine (schematic diagram, left figure) were exposed to the tissue accelerated polymerization solution separately, and dark brown polydopamine coating was observed only on the mucosal side of the tissue (middle figure), but not on the serosa side of the tissue (right figure). In order to confirm the coating specificity, sutures were used to tie both ends of the small intestinal tissue, and only the segment between the sutures was exposed to the tissue accelerated polymerization solution.

[0024] Fig.10 Catalytic Capacity Analysis of Tissue Lysates by Non-denaturing Gel Electrophoresis. Tissue lysates from different parts of the porcine gastrointestinal tract were loaded onto non-denaturing polyacrylamide gels, electrophoresed to allow protein separation, and stained for catalytic capacity analysis. Dark brown polydopamine signals were visualized on the gel after staining with tissue accelerated polymerization solution. Only one clear band (indicated by the arrow) was observed in each lane, supporting the expected role of catalase as the only enzyme responsible for polydopamine polymerization.

[0025] Fig.11 A-11B. Quantification of catalase mRNA levels in tissues using real-time PCR. Housekeeping genes, including β-actin ( Fig.11 A) and 18S( Fig.11 B) was used as a control for quantifying catalase mRNA levels. Tissue specimens from 4 pigs were tested. Fig.11 A and Fig.11 A similar distribution pattern is shown in B. Data are reported as mean ± SD of 4 animals.

[0026] Fig.12 A-12E. Ct values ​​of gene expression levels. For mRNA level quantification, catalase ( Fig.12 A), β-actin ( Fig.12 B) 18S( Fig.12 C) GUS ( Fig.12 D) and GAPDH ( Fig.12 E) Genes included in the test. Tissue specimens from 4 pigs were tested. Data are reported as mean ± SD of 4 animals.

[0027] Fig.13 .Bright field images of polydopamine coating of small intestinal epithelium. Porcine small intestinal tissue was exposed to tissue accelerated polymerization solution for 3 and 15 minutes in vitro and examined under bright field microscopy. Polydopamine was first deposited at the tips of intestinal villi (indicated by yellow arrows, upper image), and then coated the entire villus and surrounding areas (lower image). Scale bar, 500 μm.

[0028] Fig.14 A-14C. Evaluation of accelerated polymerization coating performance of in vivo tissues in the stomach. Fig.14 A shows a schematic diagram of real-time gastrointestinal endoscopy recording the stomach after oral administration of tissue accelerated polymerization solution to the stomach. The pig was in a moderate sedative state during the entire procedure. The endoscopic camera was placed outside the solution for observation and images were recorded at the same location over time. Fig.14 B shows an endoscopic image, revealing that no dark brown polydopamine was seen in the stomach. Tissue accelerated polymerization in the stomach The solution remained clear for 20 minutes. Fig.14 C shows the Fig.14 Image of isolated stomach from the animal in B confirms the absence of polydopamine coating on the epithelial surface.

[0029] Fig.15 A-15C. Evaluation of in vitro polydopamine probe tissue coating performance by X-ray imaging. Fig.15 A shows an image showing a conventional (CON) probe solution and a polydopamine probe solution. The polydopamine probe was prepared by encapsulating the conventional probe with a thin layer of polydopamine. The dark brown color of the polydopamine probe solution comes from the color-developing polydopamine on the probe surface. Fig.15 B shows a schematic diagram of the ex vivo tissue coating process. Porcine small intestine is placed in a Franz cell and tissue accelerated polymerization solution (with or without a probe) is added to the chamber. After coating, the coated tissue is rinsed with water and imaged by an X-ray system. Fig.15 C shows an X-ray image of tissues coated with a tissue accelerating polymerization solution with a polydopamine probe (left), a conventional (CON) probe (middle), and a tissue accelerating polymerization solution without a probe (right). Strong X-ray signals were observed only in the coated area (indicated by a red circle) of the tissue coated with the polydopamine probe. In the control where a single conventional probe or polydopamine was applied for coating, no obvious X-ray signals were detected.

[0030] Fig.16 A-16B. In vivo X-ray imaging of intestinal retention of polydopamine coatings. Fig.16 A shows an X-ray image revealing the stability of polydopamine coating. The tissue accelerated polymerization solution (upper figure) and conventional probe (lower figure) suspended by polydopamine probe were orally administered to healthy pigs respectively, and imaged by an X-ray system. The solution was directly applied to the small intestine through a catheter under endoscopic visual guidance. The same pigs without probe were imaged and used as controls. The imaging area was rinsed with water to test the stability of polydopamine coating. Fig.16 B shows an X-ray image revealing intestinal retention of polydopamine over time. A series of X-ray images were taken at regular intervals at the same location at 2, 6, and 24 hours. The animals always consumed a liquid diet during the imaging period, simulating real conditions and testing the stability of the polydopamine coating in the presence of food.

[0031] Fig.17 A-17B. Characterization of nano-crosslinkers. Fig.17 A shows TEM images with different magnifications, showing uniform polydopamine nanocrosslinkers. Fig.17 B depicts dynamic light scattering (DLS) analysis showing a hydrodynamic size of the nano-crosslinker of 527 nm.

[0032] Fig.18 A-18B. Evaluation of tissue accelerated polymerization coating performance across different animal species. Samples (6 mm in diameter) were collected at 3-5 random sites of polydopamine coated tissues, and images of the samples were analyzed to quantify polydopamine coatings. ImageJ was used to identify the areas of interest including polydopamine coated tissues and excluding "blank" tissue-free areas. The same analysis was performed for all samples in each group to obtain the total average polydopamine signal intensity and evaluate signal changes. This is an in vitro study. Fig.18 A shows a quantitative evaluation of the polydopamine coating density on the small intestine from pigs, humans and rats. The polydopamine signal intensity is measured after accelerated polymerization of the tissue, which represents the polydopamine coating density. Data are reported as the mean ± SD of three replicates. Fig.18 B shows quantification of catalase expression by measuring catalase activity in small intestine from pigs, humans, and rats. Fig.18 Tissue specimens were collected from the same animals as in A. Data are reported as mean ± SD of three replicates.

[0033] Fig.19 Dose-dependent cytotoxicity of polydopamine in HeLa, COLO320DM, Caco-2, Hep3B, and HS 895.T cells. Cells were treated with different concentrations of polydopamine and cytotoxicity was analyzed at different time points. After 24 h of polydopamine exposure, for all cell lines, polydopamine was added at 0–2000 μg ml -1The toxicity was low (>80% activity) within a wide concentration range.

[0034] Fig. 20 A-20C. Body weight changes of rats during the 28-day oral toxicity evaluation. Over a 4-week period, rats were exposed to water (control) ( Fig. 20 A), as prepared polydopamine ( Fig. 20 B) and tissue accelerated polymerization solution ( Fig. 20 C). No significant differences in body weight were observed between rats exposed to tissue accelerated polymerization solution, polydopamine, and water. Data were averaged (shown in black lines) between animals in each group (each animal represented by a gray line). Data are reported as mean ± SD of four animals.

[0035] Fig.21 .Hematological measurements of rat blood after 28-day oral toxicity evaluation. Blood samples were collected from rats exposed to water (control), polydopamine as prepared, and tissue accelerated polymerization solution. No significant differences in hematological parameters were observed between rats exposed to tissue accelerated polymerization solution, polydopamine, and water (four replicates).

[0036] Fig. 22 Blood biochemistry tests of rat blood after 28-day oral toxicity evaluation. Blood samples were collected from rats exposed to water (control), polydopamine as prepared, and tissue accelerated polymerization solution. No significant differences in blood biochemical parameters were observed between rats exposed to tissue accelerated polymerization solution, polydopamine, and water (four replicates).

[0037] Fig.23 .Histology of major organs collected from rats after 28 days of oral toxicity evaluation. Tissues were collected from rats exposed to water (control), polydopamine as prepared, and tissue accelerated polymerization solution, respectively. No obvious organ damage was observed in rats treated with polydopamine and tissue accelerated polymerization solution compared to the control. Scale bar, 300 μm.

[0038] Fig.24 A-24B. Evaluation of tissue accelerated polymerization properties on the epithelium after removal of bacteria present in small intestinal mucus. Samples (6 mm in diameter) were collected at 3-5 random sites of polydopamine coated tissue, and images of the samples were analyzed to quantify polydopamine coating. ImageJ was used to identify the area of ​​interest including polydopamine coated tissue and excluding "blank" tissue-free areas. The same analysis was performed on all samples in each group to obtain the overall average polydopamine signal intensity and evaluate signal changes. This was an in vitro study. Fig.24A depicts images showing tissue samples (with and without bacterial removal) after accelerated polymerization of ex vivo tissue. Samples (6 mm in diameter) were collected at three random sites on polydopamine-coated tissue. Bacteria were removed from the luminal surface of the epithelium by incubation with antibiotic-antimycotic solution and repeated washing. Fig.24 B shows Fig.24 A Quantitative measurement of polydopamine signal intensity for samples shown. Differences in intensity were not statistically significant. P > 0.05 (by two-tailed t-test). Data are reported as mean ± SD of three different tissue samples.

[0039] Fig.25 .Comparison of catalase catalytic capacity between epithelium and mucus (bacteria).The solution (180 μl) was first prepared and added to a 96-well plate, then 10 ul of tissue lysate (villus or mucus) was added. The reaction mixture was maintained at 37°C for 20 minutes. The extinction of the solution at 700 nm was measured using a plate reader (Tecan). This was an in vitro study. The relative catalytic capacity of the intestinal villi (without bacteria) was higher than that of the bacteria in the mucus. At the top of the epithelium (3 cm 2 ) Mucus was collected and epithelial villi were collected from the same tissue area. Samples were diluted to the same volume for measurement. The difference in capacity is statistically significant. ***P<0.001 (by two-tailed t-test). Data are reported as mean±SD of three different replicates.

[0040] Fig.26 A-26C. Microscopic analysis of epithelial deposition of polydopamine. 2 ) were exposed to tissue accelerated polymerization solution (10 ml) for 20 minutes and washed 3 times with PBS buffer (1X) to remove excess polydopamine. The polydopamine-coated small intestine was snap frozen and embedded in optimal cutting temperature (OCT) compound. The fixed tissue was cut into 40 μm thick sections using a cryostat (Leica Biosystems). This was an in vitro study. Fig.26 A shows bright field imaging of tissue sections coated with tissue acceleration polymerization. The dark brown polydopamine layer is deposited only on the luminal surface of epithelial cells (indicated by arrows), but not inside the cells. Fig.26 B shows a bright field image of an uncoated tissue section. The light yellow background signal comes from blood vessels. Fig.26 C shows bright field imaging of intracellular polydopamine deposition on a section of control tissue, where both dopamine and hydrogen peroxide molecules can diffuse freely and rapidly into the epithelial cells. Dark brown polydopamine deposits (indicated by arrows) are observed inside the epithelial cells, but not on the cell surface, and the deposition pattern is significantly different relative to tissue sections coated with accelerated polymerization. Scale bar, 150 μm.

[0041] Fig. 27 .Polydopamine polymerization kinetics in luminal solution.Polydopamine polymerization kinetics were evaluated in luminal solution located on top of porcine epithelium by ex vivo studies.Extinction of samples undergoing polydopamine polymerization was measured at 700 nm.Polydopamine polymerization kinetics in tissue accelerated polymerization (without epithelial catalysis) was used as a control.The optical extinction produced in 45 seconds under epithelial catalysis was the same as the extinction produced in 1 hour under control conditions.

[0042] Fig.28 .Evaluation of polydopamine signals in different cell fractionations.Cell fractionation was performed on villi coated with tissue accelerated polymerization. Villi were peeled off from the luminal surface of small intestinal tissue (opened longitudinally) placed on an ice-cold matrix. The polydopamine signal was evaluated by measuring the extinction of each cell fraction at 700nm. No polydopamine signal was detected in the cytoplasmic fraction, but a clear polydopamine signal was detected in the membrane and other fractions. The intensity difference was statistically significant. **P<0.01 (by two-tailed t-test). Data are reported as the mean ± SD of three parallel determinations.

[0043] Fig.29 . Stability evaluation of tissue accelerated polymerization in the stomach. To evaluate stability, tissue accelerated polymerization solution (dopamine (500 mg) and H2O2 (1 M, 1 mL) were quickly added to Tris buffer (50 mM, 50 mL) at pH 8.5 and used freshly) was administered to pigs (in vivo, with a non-damaging clamp applied at the pylorus), recovered from the stomach at different time points, and characterized by ex vivo coating studies. The relative coating performance showed that the recovered solution (10-30 minutes) showed consistent coating performance, and the relative coating efficiency decreased by only 30% after 60 minutes, indicating that neither dopamine nor hydrogen peroxide in tissue accelerated polymerization was absorbed or consumed in the stomach in significant amounts. Data are reported as the mean ± SD of three replicates.

[0044] Fig.30 .Evaluation of polydopamine signal in the submucosa. No detectable increase in polydopamine signal was observed in the porcine submucosa after accelerated tissue polymerization in vivo. The solution consisted of dopamine (500 mg) and H2O2 (1 M, 1 mL). Both were quickly added to Tris buffer (50 mM, 50 mL) at pH 8.5 and used fresh. Epithelial tissue (uncoated) was used as a control. The signal difference was not statistically significant. P>0.05 (by two-tailed t-test). Data are reported as mean ± SD of three replicates.

[0045] Fig.31 A-31B. Evaluation of dopamine concentrations in blood and submucosa by liquid chromatography-tandem mass spectrometry. Fig.31A shows that no significant changes in dopamine concentration were observed in the blood after in vivo administration of tissue accelerated polymerization solution (dopamine (500 mg) and H2O2 (1 M, 1 mL) were quickly added to Tris buffer (50 mM, 50 mL) at pH 8.5 and used freshly). P>0.05, two-sample t-test comparing tissue accelerated polymerization and control group (no tissue accelerated polymerization) at matched time points. Data are reported as mean ± SD of three animals. Fig.31 B shows that after application of the tissue accelerating polymerization solution (after 3 hours), no detectable increase in dopamine concentration was observed in the submucosal layer. The concentration difference was not statistically significant. P>0.05 (by two-tailed t-test). Data are reported as mean ± SD of three replicates.

[0046] Fig.32 A-32D. Evaluation of blocking efficiency of tissue accelerated polymerization layer by in vitro study. Tissue was exposed to solution (dopamine (500 mg) and H2O2 (1 M, 1 ml) were quickly added to Tris buffer (50 mM, 50 ml) at pH 8.5, and the mixed solution was used fresh) and washed 3 times with PBS buffer (1X) to remove excess polydopamine. Polydopamine nanocrosslinkers of different concentrations (25 mg / ml, 12.5 mg / ml and 0 mg / ml) were suspended in tissue accelerated polymerization solution. This is an in vitro study. Fig.32 A-32C shows the tissue-accelerated polymerization layer on Ca 2+ ( Fig.32 A) Glutamate ( Fig.32 B) and glucose ( Fig.32 C) relative barrier function (tissue permeability). All three nutrients showed reduced tissue permeability, with three separate experiments showing that the tissue accelerated polymerisation barrier blocked approximately 49% of Ca 2+ , about 71% glutamate and about 78% glucose. Fig.32 D shows the relative barrier function (glucose tissue permeation) of tissue accelerating polymer layers (with different cross-linking densities). When less nano-cross-linking agent was introduced into the coating layer, glucose had normal tissue permeation levels, indicating that the polydopamine coating layer itself did not affect cellular glucose absorption, but the cross-linking density of the coating layer regulated the glucose absorption efficiency. Porcine small intestine tissue (no coating) was used as a control. *P < 0.05 (relative to control), one-way analysis of variance (ANOVA) and post hoc Bonferroni. Data are reported as mean ± SD of three parallel determinations.

[0047] Fig.33.Evaluation of recovery of glucose absorption in tissue accelerated polymerization animals. First, the polydopamine nano cross-linker (25 mg / ml) was suspended in a tissue accelerated polymerization solution. The nano cross-linker-suspended tissue accelerated polymerization solution (10 ml / kg) was orally administered to pigs and introduced into the small intestine. The solution was directly applied to the small intestine through a catheter under endoscopic visual guidance. This is an in vitro study. An oral glucose tolerance test was performed 24 hours after the pigs received the tissue accelerated polymerization coating. Pigs with tissue accelerated polymerization coating recovered normal glucose absorption after 24 hours, indicating that the tissue accelerated polymerization coating layer is transient. The data between animals in each group (each animal is represented by a gray line) were averaged (shown with a black line).

[0048] Fig.34 . Evaluation of CYP450 activity in epithelial cells with and without polydopamine coating. 2 ) were exposed to tissue accelerated polymerization solution (10 ml) for 20 minutes and washed 3 times with PBS buffer (1x) to remove excess polydopamine. This is an in vitro study. No changes in CYP3A4 activity were observed in the epithelium after tissue accelerated polymerization. Epithelial tissue (uncoated) was used as a control. The activity differences were not statistically significant. P>0.05 (by two-tailed t-test). Data are reported as mean ± SD of five replicates.

[0049] Fig.35 A-35B. Accelerated polymerization model of tissue in human GI tract. 2 ) were exposed to tissue accelerating polymerization solution (10 ml) for 20 minutes and washed 3 times with PBS buffer (1X) to remove excess polydopamine. This was an in vitro study. Fig.35 A depicts images showing human tissue samples in different parts of the GI tract before and after ex vivo application of tissue accelerated polymerization coating. Samples (6 mm in diameter) were collected at three random sites of the polydopamine coated tissue. Fig.35 B shows Fig.35 Quantitative measurement of polydopamine signal intensity for samples shown in A. Differences in intensity between small intestine and other tissues are statistically significant. *P<0.05, one-way analysis of variance (ANOVA) with post hoc Bonferroni. Data are reported as mean±SD of three different tissue samples.

[0050] Fig.36A-36C. Stability of surface-based polydopamine coating. A polydopamine coating was applied to the surface of an impermeable polycarbonate substrate. The polycarbonate sheets were exposed to a tissue-accelerated polymerization solution (without H2O2) for 36 hours and washed with water to remove excess polydopamine. The white polycarbonate (left) turned dark brown after polydopamine coating (right). The stability of the polydopamine coating was evaluated under a range of physical conditions. Fig.36 A-36C showed that no significant reduction in polydopamine signal was observed under both mild and vigorous scraping, and the polydopamine coating was removed only under extremely vigorous scraping with sandpaper. These results indicate that the stability of the surface-based polydopamine coating is due to strong surface-based adhesion rather than penetration into the substrate surface.

[0051] Fig.37 .Transformation of tissue accelerated polymerization platform into capsules. Porcine small intestine tissue isolated from the body showed different polydopamine coatings before and after the clamping site, indicating the coating performance of the tissue accelerated polymerization capsule. The capsule consists of dopamine hydrochloride powder (500 mg), Tris powder (30-300 mg; 300 mg), and solid urea H2O2 powder (10-50 mg; 50 mg). The mixed powder is filled into (No. 000) capsules. A hole is surgically opened in the intestine and the capsule is directly applied to the intestine for capsule delivery. Due to the ligation of the small intestine, the capsule cannot be passed down to the lower small intestine. After releasing the tissue accelerated polymerization component, the capsule collapses, dissolves and breaks into smaller pieces.

[0052] definition

[0053] Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0054] The language "in some embodiments" and "in certain embodiments" are used interchangeably.

[0055] The following definitions are of more general terms used throughout this application:

[0056] The singular terms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise.

[0057] Except in the examples, or where otherwise indicated, all numerals used herein that represent the amount of a component or reaction condition are to be understood as being modified in all cases by the term "about". "About" and "approximately" are generally intended to mean an acceptable degree of error for the amount measured according to the nature or precision of the measurement. Exemplary degrees of error are within 20% (percentage) of a given value or range of values, typically within 10%, or more typically within 5%, 4%, 3%, 2%, or 1%.

[0058] When a range of values ​​("range") is listed, it is intended to include every value and sub-range within that range. A range includes values ​​at both ends of the range unless otherwise provided.

[0059] The terms "composition" and "formulation" are used interchangeably.

[0060] The "subject" intended for administration refers to a human (i.e., a male or female of any age, such as a pediatric subject (e.g., an infant, child, or adolescent) or an adult subject (e.g., a young, middle-aged, or elderly person)) or a non-human animal. In certain embodiments, the non-human animal is a mammal (e.g., a primate (e.g., a cynomolgus monkey or a rhesus monkey), a commercially relevant mammal (e.g., a cow, pig, horse, sheep, goat, cat, or dog) or a bird (e.g., a commercially relevant bird, such as a chicken, duck, goose, or turkey)). In certain embodiments, the non-human animal is a fish, a reptile, or an amphibian. The non-human animal can be male or female at any stage of development. The non-human animal can be a transgenic animal or a genetically engineered animal. The term "patient" refers to a human subject in need of treatment for a disease.

[0061]

[00136] The terms "administer," "administering," or "administration" refer to implanting, absorbing, ingesting, injecting, inhaling, or otherwise introducing a composition described herein into or onto a subject.

[0062] The terms "treatment", "treat" and "treating" refer to reversing, alleviating, delaying the onset of a disease described herein, or inhibiting the progression of a disease described herein. In some embodiments, treatment may be administered after one or more signs or symptoms of a disease have developed or been observed. In other embodiments, treatment may be administered when there are no signs or symptoms of a disease. For example, treatment may be administered to a susceptible subject prior to the onset of symptoms (e.g., based on a history of symptoms and / or based on exposure to a pathogen). Treatment may also be continued after symptoms resolve, for example, to delay or prevent recurrence.

[0063] The terms "condition," "disease," and "disorder" are used interchangeably.

[0064] The "effective amount" of a polymer or composition as described herein refers to an amount sufficient to cause a desired biological response. The effective amount of a polymer or composition as described herein can vary according to the following factors: the desired biological endpoint, the pharmacokinetics of the polymer or composition, the disease treated, the mode of administration, and the age and health status of the subject. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a preventive treatment. In certain embodiments, the effective amount is the amount of a single dose of a compound, polymer, or composition as described herein. In certain embodiments, the effective amount is the combined amount of multiple doses of a compound, polymer, or composition as described herein.

[0065] The term "cancer" refers to a class of diseases characterized by the development of abnormal cells that proliferate uncontrollably and have the ability to infiltrate and destroy normal body tissues. See, e.g., Stedman's Medical Dictionary, 25th ed.; Hensyl, ed.; Williams & Wilkins: Philadelphia, 1990.

[0066] "Autoimmune disease" refers to a disease caused by an inappropriate immune response by the subject's body to substances and tissues normally present in the body. In other words, the immune system mistakes certain parts of the body for pathogens and attacks its own cells. This may be limited to certain organs (e.g., in autoimmune thyroiditis) or involve specific tissues in different locations (e.g., Goodpasture's disease, which may affect the basement membranes in both the lungs and kidneys). Treatment of autoimmune diseases typically employs immunosuppression, such as drugs that reduce the immune response.

[0067] The term "inflammatory disease" refers to a disease caused by, resulting from, or causing inflammation. The term "inflammatory disease" may also refer to an unregulated inflammatory response that causes an overreaction of macrophages, granulocytes, and / or T lymphocytes, leading to abnormal tissue damage and / or cell death. Inflammatory diseases may be acute or chronic inflammatory conditions and may be caused by infectious or non-infectious causes.

[0068] The term "polymer" refers to a compound comprising eleven or more covalently linked repeating units. In certain embodiments, the polymer is naturally occurring. In certain embodiments, the polymer is synthetic (i.e., non-naturally occurring).

[0069] The term "nanoparticle" refers to particles having an average (e.g., mean) size (e.g., diameter) of about 1 nanometer (nm) to about 1 micrometer (μm), inclusive (e.g., about 1 nm to about 300 nm, about 1 nm to about 100 nm, about 1 nm to about 30 nm, about 1 nm to about 10 nm, or about 1 nm to about 3 nm).

[0070] As used herein, the term "agent" means a molecule, a group of molecules, a complex or a substance administered to an organism for diagnosis, treatment, preventive medicine or veterinary purposes. In certain embodiments, the agent is an active pharmaceutical ingredient agent, a diagnostic agent or a preventive agent. In certain embodiments, the polymers and compositions disclosed herein include one or more agents, such as a first agent (e.g., at least one (including, for example, at least two, at least three)). In some embodiments, the polymers and compositions may also include a second agent. In some embodiments, the agent is an enzyme (e.g., a digestive enzyme), a nutrient blocker (e.g., a cross-linking agent), a diagnostic agent, a nutritional preparation, a radiation protectant, an active pharmaceutical ingredient, or a combination thereof.

[0071] As used herein, the term "radioprotectant" means an agent that protects biological systems exposed to radiation, either naturally or through radiation leakage. In certain embodiments, the radioprotectant protects normal cells of cancer patients undergoing radiation therapy from radiation damage.

[0072] As used herein, the term "diagnostic agent" means an imaging agent or a contrast agent. The terms "imaging agent" and "contrast agent" refer to substances used in medical imaging to enhance the contrast of structures or fluids in the body. They are typically used to enhance the visibility of blood vessels and the gastrointestinal tract in medical imaging.

[0073] As used herein, the term "active pharmaceutical ingredient" includes agents that are capable of providing a local or systemic biological, physiological, or therapeutic effect in a biological system to which it is applied. For example, active pharmaceutical ingredients can be used to control tumor growth, control infection or inflammation, act as an analgesic, promote anti-cell adhesion, and enhance bone growth, among other functions. Other suitable active pharmaceutical ingredients may include antiviral agents, hormones, antibodies, or therapeutic proteins. Other active pharmaceutical ingredients include prodrugs, i.e., agents that are not biologically active when administered, but are converted to biologically active agents by metabolism or some other mechanism after administration to a subject.

[0074] The active pharmaceutical ingredient can be a compound, such as an organic or inorganic small molecule; saccharin; an oligosaccharide; a polysaccharide; a biological macromolecule, such as a peptide, a protein, and a peptide analog and derivative; a peptidomimetic; an antibody and an antigen-binding fragment thereof; a nucleic acid; a nucleic acid analog and derivative; an extract made from biological material such as bacteria, plants, fungi, or animal cells; an animal tissue; a naturally occurring or synthetic composition; and any combination thereof.

[0075] Examples of active pharmaceutical ingredients include, but are not limited to, antimicrobial agents, analgesics, anti-inflammatory agents, anti-irritants, coagulation regulators, diuretics, sympathomimetics, anorectics, antacids and other gastrointestinal agents; antiparasitic agents, antidepressants, hypotensive agents, anticholinergic agents, stimulants, antihormones, central and respiratory stimulants, drug antagonists, lipid regulators, uricosuric agents, cardiac glycosides, electrolytes, ergot and its derivatives, expectorants, hypnotics and sedatives, antidiabetic agents, dopaminergic agents, antiemetics, muscle relaxants, parasympathomimetics, antispasmodics, antihistamines, beta blockers, cathartics, antiarrhythmics, contrast agents, radiopharmaceuticals, antiallergic agents, tranquilizers, vasodilators, antivirals, and antitumor agents or cytostatics or other agents with anticancer properties, or combinations thereof. Other suitable active pharmaceutical ingredients include contraceptives and vitamins and micro- and macronutrients. Other examples include anti-infective agents, such as antibiotics and antivirals; analgesics and analgesic combinations; anorectics; anti-helmintics; anti-arthritics; antitussives; antispasmodics; antidepressants; antidiuretics; antidiarrheals; antihistamines; anti-inflammatory agents; anti-migraine preparations; antinauseants; antineoplastic agents; anti-Parkinson's disease drugs; antipruritics; antipsychotics; antipyretics, antispasmodics; anticholinergics; sympathomimetics; xanthine derivatives; cardiovascular agents, including calcium channel blockers and beta blockers, such as indole; Dolol and antiarrhythmics; antihypertensives; diuretics; vasodilators (including general coronary, peripheral and cerebral); central nervous system stimulants; cough and cold preparations, including decongestants; hormones such as estradiol and other steroids, including corticosteroids; hypnotics; immunosuppressants; muscle relaxants; parasympathetic blocking agents; psychostimulants; sedatives; and tranquilizers; and naturally derived or genetically engineered proteins, polysaccharides, glycoproteins, or lipoproteins.

[0076] Detailed description of certain embodiments

[0077] Before describing the disclosed systems, compositions, methods, uses, and kits in more detail, it should be understood that the aspects described herein are not limited to specific embodiments, methods, systems, devices, or configurations, and thus may of course vary. It should also be understood that the terminology used herein is for the purpose of describing particular aspects only, and is not intended to be limiting unless specifically defined herein.

[0078] Generally speaking, polydopamine polymerization is a slow process, and under normal dopamine oxidation conditions, its reaction rate is limited by low oxygen levels. 11However, the present inventors unexpectedly discovered that the generation of defensive oxygen via the decomposition of hydrogen peroxide by endogenous catalase (known as the cellular antioxidant effect) promoted the release of oxygen for dopamine oxidation and significantly increased the rate of dopamine polymerization. Figure 1 A shows a schematic diagram of an embodiment of the present disclosure, in which an oral monomer solution containing dopamine monomers and hydrogen peroxide is administered to a subject. The solution flows uninhibitedly on the surface of the gastrointestinal mucosa, and the hydrogen peroxide molecules diffuse freely between the epithelial tissue and the dopamine solution. However, dopamine remains in the solution due to its slow diffusion and transport. Hydrogen peroxide diffuses into epithelial cells and is rapidly decomposed into oxygen by intracellular catalase, which is released from the cells and mixed with extracellular monomers. These monomers close to the epithelial surface are rapidly oxidized into oligomers and further oxidized into polymers, which cross-link with biomolecules exposed to the outside of the epithelium to form a thin, strong polydopamine coating on the tissue. Unreacted monomers and unbound polydopamine in the solution are washed away from the epithelium. This type of tissue surface-induced polymer coating avoids potential intestinal adhesions and obstructions, which are often induced by bulk-crosslinking-based sealants or other conventional tissue adhesives. 13 Catalytic polydopamine polymerization occurs primarily in the small intestine, due to the higher expression levels of catalase in the small intestine compared to other parts of the gastrointestinal tract (including the esophagus, stomach, and large intestine). Therefore, specific small intestinal targeting can be achieved spontaneously due to the uneven distribution of the native enzyme along the digestive tract.

[0079] The inventor has performed a series of studies involving compositions, methods and kits disclosed herein. The inventor uses various techniques, including endoscopy, intestinal ligation and X-ray imaging, which consistently show the robustness of the subject, indicating the characteristics of the polymer formed in situ (extended but transient intestinal retention). In addition, the inventor has not observed any clinical, endoscopic, or radiographic evidence of gastrointestinal perforation, inflammation, or obstruction related to the use of compositions, methods and kits disclosed herein. The biocompatibility of some compositions disclosed herein is carefully characterized by following the guidelines issued by the Organization for Economic Cooperation and Development (OECD) and confirming that there is no oral toxicity.

[0080] Methods and uses

[0081] In one aspect, the present disclosure provides a method of forming a polymer in situ in a subject, the method comprising administering to the subject a composition comprising a monomer and an oxygen source, wherein the monomer and the oxygen source contact a catalyst endogenous to the subject and the catalyst polymerizes the monomer, wherein the monomer is dopamine or a salt thereof, the oxygen source is hydrogen peroxide or urea hydrogen peroxide, and the endogenous catalyst is selected from catalase or peroxidase.

[0082] In some embodiments, the endogenous catalyst is a peroxidase. In certain embodiments, the peroxidase is eosinophil peroxidase, lactoperoxidase, or myeloperoxidase.

[0083] In some embodiments, the endogenous catalyst is catalase. In some embodiments, the catalase is bacterial catalase. In some embodiments, the catalase is human catalase.

[0084] In some embodiments, the endogenous catalyst is located in the subject's gastrointestinal (GI) tract. In some embodiments, the endogenous catalyst is located in the subject's upper GI tract. In some embodiments, the endogenous catalyst is located in the subject's intestines. In some embodiments, the endogenous catalyst is located in the subject's stomach.

[0085] In some embodiments, the endogenous catalyst is located in a cell. In some embodiments, the endogenous catalyst is located in a blood cell. In some embodiments, the endogenous catalyst is located on a cell. In some embodiments, the endogenous catalyst is located on a blood cell. In some embodiments, the endogenous catalyst is located in a cell. In some embodiments, the endogenous catalyst is secreted by a blood cell. In some embodiments, the endogenous catalyst is located on a cell. In some embodiments, the endogenous catalyst is secreted by a blood cell.

[0086] In some embodiments, the composition further comprises an enzyme, a nutrient blocker, a radiation protectant, a nutritional preparation, an active pharmaceutical ingredient, a diagnostic agent, or a combination thereof. In some embodiments, the composition further comprises an enzyme. In some embodiments, the composition further comprises a nutrient blocker. In some embodiments, the composition further comprises a radiation protectant. In some embodiments, the composition further comprises an active pharmaceutical ingredient. In some embodiments, the composition further comprises a diagnostic agent. In some embodiments, the composition further comprises a combination of two or more of an enzyme, a nutrient blocker, a nutritional preparation, a radiation protectant, an active pharmaceutical ingredient, and a diagnostic agent.

[0087] In some embodiments, the oxygen source is hydrogen peroxide. In some embodiments, the oxygen source is urea hydrogen peroxide.

[0088] In some embodiments, at least one of the monomer and the source of oxygen is stable in the stomach of a subject. In some embodiments, at least one of the monomer and the source of oxygen is stable in the stomach of a subject for at least 30 minutes. In some embodiments, at least one of the monomer and the source of oxygen is stable in the stomach of a subject for at least 60 minutes.

[0089] In some embodiments, the composition is stable in the stomach of the subject. In some embodiments, the composition is stable in the stomach of the subject for at least 30 minutes. In some embodiments, the composition is stable in the stomach of the subject for at least 60 minutes.

[0090] In some embodiments, at least one of the monomer and the source of oxygen is stable in that it does not decompose in the stomach of a subject. In some embodiments, at least 95% of at least one of the monomer and the source of oxygen is still present after the composition is discharged from the stomach of a subject. In some embodiments, at least 90% of at least one of the monomer and the source of oxygen is still present after the composition is discharged from the stomach of a subject. In some embodiments, at least 80% of at least one of the monomer and the source of oxygen is still present after the composition is discharged from the stomach of a subject.

[0091] In some embodiments, the composition comprises about 0.001 to about 1000 mg / mL of dopamine. In some embodiments, the composition comprises about 0.01 to about 100 mg / mL of dopamine. In some embodiments, the composition comprises about 0.01 to about 50 mg / mL of dopamine. In some embodiments, the composition comprises about 1 to about 20 mg / mL of dopamine. In some embodiments, the composition comprises 10 mg / mL of dopamine. In some embodiments, the composition comprises 9.8 mg / mL of dopamine.

[0092] In some embodiments, the composition comprises about 0.01 to about 100 mM of an oxygen source. In some embodiments, the composition comprises about 0.1 to about 50 mM of an oxygen source. In some embodiments, the composition comprises about 1 to about 30 mM of an oxygen source. In some embodiments, the composition comprises about 20 mM of an oxygen source.

[0093] In some embodiments, the composition comprises an oxygen source at a concentration compatible with ingestion by a subject.

[0094] In certain embodiments, the composition further comprises a buffer.

[0095] In some embodiments, the composition has a pH of about 7 to about 10. In some embodiments, the composition has a pH of about 7 to about 9. In some embodiments, the composition has a pH of about 8.5. In some embodiments, the composition has a pH of about 7.4.

[0096] In some embodiments, the composition is administered by a route selected from oral, rectal, injection, sublingual, buccal, vaginal, ocular, ear, inhalation, or skin. In some embodiments, the composition is administered orally. In certain embodiments, the composition is administered by intra-articular injection. In certain embodiments, the composition is administered topically. In certain embodiments, the composition is administered dermally. In certain embodiments, the composition is administered ocularly.

[0097] In some embodiments, the composition is administered via a scope. In certain embodiments, the composition is administered via an endoscope, arthroscopy, cystoscope, colposcope, colonoscope, bronchoscope, ureteroscope, anoscope, esophagoscope, gastroscope, laparoscope, laryngoscope, neuroendoscope, proctoscopy, sigmoidoscope, or thoracoscope.

[0098] In some embodiments, the composition is in liquid or solid dosage form.

[0099] In some embodiments, the composition is in the form of a solution, gel, tablet, powder, capsule, eye drops, or a transdermal patch. In some embodiments, the composition is in the form of a solution, gel, tablet, or capsule. In some embodiments, the composition is in the form of a solution. In some embodiments, the composition is in the form of eye drops. In some embodiments, the composition is in the form of a powder. In some embodiments, the composition is in the form of a transdermal patch.

[0100] In certain embodiments, the polymer forms and adheres to tissue in a subject upon contact with the tissue. In some embodiments, the polymer adheres to the tissue of the subject. In certain embodiments, the tissue is epithelium. In some embodiments, the epithelium is intestinal epithelium.

[0101] In some embodiments, the location of polymer formation is based on the expression level of the catalyst. In certain embodiments, the polymer is substantially formed on a specific tissue based on a high expression level of the catalyst. In some embodiments, the polymer is substantially not formed on a specific tissue due to a low expression level of the catalyst. In some embodiments, the location of polymer formation is based on the expression level of catalase. In certain embodiments, the polymer is substantially formed on a specific tissue based on the expression level of catalase. In some embodiments, the polymer is substantially not formed on a specific tissue due to a low expression level of catalase.

[0102] In certain embodiments, the tissue is epithelium. In certain embodiments, the polymer is formed on the epithelium of the subject and adheres to the epithelium. In certain embodiments, the polymer is formed when in contact with the epithelium of the subject. In certain embodiments, the epithelium is intestinal epithelium. In certain embodiments, the polymer is formed on the small intestine. In certain embodiments, the polymer is formed in the lumen of the small intestine. In certain embodiments, the polymer is formed on the duodenal epithelium of the subject.

[0103] In some embodiments, the polymer binds to an amine moiety exposed on the luminal surface of an epithelium of a subject. In some embodiments, the polymer cross-links to an amine moiety exposed on the luminal surface of an epithelium of a subject.

[0104] In some embodiments, the polymer forms quickly. In some embodiments, the polymer forms in less than about 20 minutes. In some embodiments, the polymer forms in less than about 15 minutes. In some embodiments, the polymer forms in less than about 12 minutes. In some embodiments, the polymer forms in less than about 10 minutes. In some embodiments, the polymer forms in less than about 5 minutes. In some embodiments, the polymer forms in less than about 3 minutes. In some embodiments, the polymer forms in less than about 2 minutes. In some embodiments, the polymer forms in less than about 1 minute. In some embodiments, the polymer forms almost immediately.

[0105] In some embodiments, the polymerization rate is increased by at least 10 times compared to polymer formation in the absence of endogenous catalase. In some embodiments, the polymerization rate is increased by at least 50 times compared to polymer formation in the absence of endogenous catalase. In some embodiments, the polymerization rate is increased by at least 100 times compared to polymer formation in the absence of endogenous catalase. In some embodiments, the polymerization rate is increased by at least 150 times compared to polymer formation in the absence of endogenous catalase. In some embodiments, the polymerization rate is increased by at least 200 times compared to polymer formation in the absence of endogenous catalase.

[0106] In some embodiments, the polymer is formed on the epithelium of the gastrointestinal tract of the subject. In some embodiments, the polymer is formed on the epithelium of the small intestine of the subject.

[0107] In some embodiments, the polymer does not form on the epithelium of the gastrointestinal tract outside of the small intestine of the subject.

[0108] In some embodiments, the polymer is formed on the epithelium of one or more of the duodenum, jejunum, ileum, colon, esophagus, or stomach of the subject. In some embodiments, the polymer is formed on the duodenal epithelium of the subject. In some embodiments, the polymer is formed on the jejunal epithelium of the subject. In some embodiments, the polymer is formed on the ileal epithelium of the subject. In some embodiments, the polymer is formed on the colonic epithelium of the subject.

[0109] In some embodiments, the polymer is substantially not formed on the epithelium of one or more of the esophagus or stomach of the subject. In some embodiments, substantially no polymer is formed on the stomach and esophagus of the subject. In some embodiments, the polymer is not formed on the stomach and esophagus of the subject.

[0110] In some embodiments, less polymer is formed in the ileum and colon of the subject compared to the duodenum and jejunum of the subject.

[0111] In some embodiments, the polymer is formed on epithelial villi of a subject.

[0112] In some embodiments, the polymer forms a temporary barrier in vivo. In some embodiments, the polymer forms a transient barrier in vivo.

[0113] In some embodiments, the polymer lasts for about 30 minutes. In some embodiments, the polymer lasts for about 1 hour. In some embodiments, the polymer lasts for about 6 hours. In some embodiments, the polymer lasts for about 12 hours. In some embodiments, the polymer lasts for about 24 hours.

[0114] In some embodiments, after 12 hours, about 20% to about 70% of the transient barrier remains. In some embodiments, after 12 hours, about 30% to about 50% of the transient barrier remains. In some embodiments, after 12 hours, about 20% of the transient barrier remains.

[0115] In some embodiments, after 6 hours, about 20% to about 70% of the transient barrier remains.

[0116] In some embodiments, after 6 hours, about 30% to about 50% of the transient barrier remains.

[0117] In some embodiments, after 6 hours, about 20% of the transient barrier is still present. In some embodiments, after 3 hours, about 20% to about 70% of the transient barrier is still present. In some embodiments, after 3 hours, about 30% to about 50% of the transient barrier is still present. In some embodiments, after 3 hours, about 20% of the transient barrier is still present.

[0118] In some embodiments, the polymer is cleared from the subject after about 3 hours. In some embodiments, the polymer is cleared from the subject after about 6 hours. In some embodiments, the polymer is cleared from the subject after about 12 hours. In some embodiments, the polymer is cleared from the subject after about 24 hours. In some embodiments, the polymer is cleared from the subject after about 48 hours.

[0119] In some embodiments, the polymeric barrier provides for selective transport of molecules across the patient's epithelium.

[0120] In some embodiments, the method is a method of regulating intestinal diffusion in a subject. In some embodiments, the method regulates the diffusion of one or more of a salt, ion, water, oxygen, carbon dioxide, carbonate anion, acid, base, carbohydrate, lipid, protein, nucleic acid, nutrient, or active pharmaceutical ingredient in a subject.

[0121] In some embodiments, the polymer modulates the absorption of one or more nutrients or active pharmaceutical ingredients in the small intestine.

[0122] In some embodiments, the polymer substantially blocks absorption of one or more nutrients into the epithelium on which the polymer is formed, the intestinal wall of the subject, or the bloodstream of the subject.

[0123] In some embodiments, the method is a method of delivering an agent to a subject. In some embodiments, the agent is an active pharmaceutical ingredient. In some embodiments, the agent is an enzyme. In some embodiments, the agent is a radioprotectant. In some embodiments, the agent is delivered to the intestine.

[0124] In some embodiments, the method enables sustained release of an agent in a subject. In some embodiments, the agent is an active pharmaceutical ingredient. In some embodiments, the agent is an enzyme. In some embodiments, the agent is a radioprotectant. In some embodiments, sustained release occurs in the GI tract.

[0125] In some embodiments, the method is a method of fixing an agent in a subject. In some embodiments, the agent is an active pharmaceutical ingredient. In some embodiments, the agent is an enzyme. In some embodiments, the agent is a radioprotectant. In some embodiments, the agent is fixed in the GI tract.

[0126] In some embodiments, the method is a method of locally delivering an agent in a subject. In some embodiments, the agent is an active pharmaceutical ingredient. In some embodiments, the agent is an enzyme. In some embodiments, the agent is a radioprotectant. In some embodiments, local delivery occurs in the GI tract.

[0127] In some embodiments, the method is a method of reducing the frequency of administration of an agent. In some embodiments, the agent is an active pharmaceutical ingredient. In some embodiments, the agent is an enzyme. In some embodiments, the agent is a radioprotectant.

[0128] In some embodiments, the method is a method of increasing the half-life of an agent in a subject. In some embodiments, the agent is an active pharmaceutical ingredient. In some embodiments, the agent is an enzyme. In some embodiments, the agent is a radioprotectant.

[0129] In some embodiments, the method is a method of increasing the residence time of an agent in a subject. In some embodiments, the agent is an active pharmaceutical ingredient. In some embodiments, the agent is an enzyme. In some embodiments, the agent is a radioprotectant. In some embodiments, the method is a method of increasing the residence time of an agent in the GI tract.

[0130] In some embodiments, the method is a method of treating or preventing a disease in a subject. In some embodiments, the method is a method of treating a disease in a subject. In some embodiments, the method is a method of preventing a disease in a subject.

[0131] In some embodiments, the method is a method of aiding tissue restoration and regeneration at a polymerization site in a subject. In some embodiments, the method is a method of aiding tissue restoration at a polymerization site in a subject. In some embodiments, the method is a method of aiding tissue regeneration at a polymerization site in a subject.

[0132] In some embodiments, the method maintains the intestinal lumen of the subject distended.

[0133] In some embodiments, the method is a method of preventing intestinal adhesions in a subject.

[0134] In some embodiments, the method is a method of preventing intestinal obstruction in a subject.

[0135] In some embodiments, the method is a method of treating bleeding in a subject. In some embodiments, the bleeding is in the upper GI tract.

[0136] In some embodiments, the polymers and compositions further comprise an enzyme. In some embodiments, the enzyme is a digestive enzyme. In some embodiments, the digestive enzyme is lactase, peptidase, sucrase, maltase, amylase, lipase, or protease. In some embodiments, the digestive enzyme is β-galactosidase.

[0137] In some embodiments, the method is a method of increasing digestive efficiency in a subject.

[0138] In some embodiments, the method is a method of enhancing digestion of sugars in a subject. In some embodiments, the method is a method of enhancing digestion of lactose in a subject.

[0139] In some embodiments, the method is a method of treating lactose intolerance in a subject.

[0140] In some embodiments, the enzyme increases the digestion efficiency of sugar by about 5 times in a subject. In some embodiments, the enzyme increases the digestion efficiency of sugar by about 10 times in a subject. In some embodiments, the enzyme increases the digestion efficiency of sugar by about 20 times in a subject. In some embodiments, the enzyme increases the digestion efficiency of lactose by about 40 times in a subject. In some embodiments, the enzyme increases the digestion efficiency of sugar by about 50 times in a subject.

[0141] In some embodiments, the β-galactosidase increases the efficiency of lactose digestion by a subject by about 5 times. In some embodiments, the β-galactosidase increases the efficiency of lactose digestion by a subject by about 10 times. In some embodiments, the β-galactosidase increases the efficiency of lactose digestion by a subject by about 20 times. In some embodiments, the β-galactosidase increases the efficiency of lactose digestion by a subject by about 40 times. In some embodiments, the β-galactosidase increases the efficiency of lactose digestion by a subject by about 50 times.

[0142] In some embodiments, the polymeric barrier does not inhibit the intrinsic digestive enzyme activity of the epithelium of the subject.

[0143] In some embodiments, the polymers and compositions further comprise a nutrient blocking agent.

[0144] In some embodiments, the method is a method of preventing nutrient absorption in a subject.

[0145] In some embodiments, the method is a method for regulating or controlling the sugar absorption of a subject. In some embodiments, the sugar is selected from glucose, lactose, fructose, maltose, dextrose, galactose, sucrose and isomaltose. In some embodiments, the method is a method for regulating or controlling the glucose absorption of a subject.

[0146] In some embodiments, the method prevents absorption for less than about 48 hours. In some embodiments, the method prevents absorption for less than about 24 hours. In some embodiments, the method prevents absorption for less than about 12 hours. In some embodiments, the method prevents absorption for less than about 6 hours. In some embodiments, the method prevents absorption for less than about 3 hours.

[0147] In some embodiments, the method is a method of treating obesity in a subject.

[0148] In some embodiments, the method is a method of treating hyperinsulinemia in a subject.

[0149] In some embodiments, the method is a method of treating diabetes in a subject. In some embodiments, the diabetes is type 2 diabetes.

[0150] In some embodiments, the composition further comprises a cross-linking agent.

[0151] In some embodiments, the crosslinking agent comprises nanoparticles. In some embodiments, the crosslinking agent comprises polydopamine. In some embodiments, the crosslinking agent is a nutrient blocking agent. In some embodiments, the crosslinking agent increases the nutrient blocking ability of the polymer.

[0152] In some embodiments, glucose absorption is regulated by adjusting the cross-linking density of the polymer. In some embodiments, the method makes the glucose absorption of the subject decrease by at least about 50%, at least about 60%, or at least about 70% in a period of 3 hours after the composition is applied. In some embodiments, the method makes the glucose absorption of the subject decrease by at least about 70% in a period of 3 hours after the composition is applied. In some embodiments, the method makes the glucose absorption of the subject decrease by at least about 50%, at least about 60%, or at least about 70% in a period of 2 hours after the composition is applied. In some embodiments, the method makes the glucose absorption of the subject decrease by at least about 50%, at least about 60%, or at least about 70% in a period of 1 hour after the composition is applied.

[0153] In some embodiments, the method is a method of regulating or modulating nutrient intake in a subject.

[0154] In some embodiments, the composition further comprises an active pharmaceutical ingredient. In some embodiments, the active pharmaceutical ingredient is an antiparasitic drug. In some embodiments, the active pharmaceutical ingredient is an anthelmintic. In some embodiments, the active pharmaceutical ingredient is praziquantel.

[0155] In some embodiments, the composition further comprises an active pharmaceutical ingredient. In some embodiments, the active pharmaceutical ingredient is an agent for treating infectious diseases. In some embodiments, the active pharmaceutical ingredient is an antiparasitic. In some embodiments, the active pharmaceutical ingredient is an anthelmintic. In some embodiments, the active agent is an antiparasitic. In some embodiments, the active pharmaceutical ingredient is praziquantel. In some embodiments, the active agent is an antiviral. In some embodiments, the active agent treats influenza. In some embodiments, the active agent treats type 2 diabetes. In some embodiments, the active agent treats eye diseases. In some embodiments, the active agent treats Crohn's disease. In some embodiments, the active agent treats osteoarthritis. In some embodiments, the active agent treats Alzheimer's disease.

[0156] In some embodiments, the active pharmaceutical ingredient treats a psychiatric disorder, Alzheimer's disease, an infectious disease, or transplant rejection. In certain embodiments, the active pharmaceutical ingredient is a contraceptive, a statin, a blood pressure lowering agent, or an antibiotic.

[0157] In some embodiments, active pharmaceutical ingredient. In some embodiments, active pharmaceutical ingredient is anticancer agent. Anticancer agent covers biological therapeutic anticancer agent and chemotherapeutic agent. Exemplary biological therapeutic anticancer agent includes but is not limited to interferon, cytokine (for example, tumor necrosis factor, interferon α, interferon γ), vaccine, hematopoietic growth factor, monoclonal serum therapy, immunostimulant and / or immunomodulator (for example, IL-1, 2, 4, 6 or 12), immune cell growth factor (for example, GM-CSF) and antibody (for example HERCEPTIN (trastuzumab), T-DM1, AVASTIN (bevacizumab), ERBITUX (cetuximab), VECTIBIX (panitumumab), RITUXAN (rituximab), BEXXAR (tositumomab)). Exemplary chemotherapeutic agents include, but are not limited to, antiestrogens (e.g., tamoxifen, raloxifene, and megestrol acetate), LHRH agonists (e.g., goserelin and leuprolide), antiandrogens (e.g., flutamide and bicalutamide), photodynamic therapy (e.g., vertoporfin (BPD-MA), phthalocyanine, photosensitizer Pc4, and desmethoxy-hypocrellin A (2BA-2-DMHA)), nitrogen mustards (e.g., cyclophosphamide, ifosfamide, trofosfamide, chlorambucil, estramustine, and melphalan), nitrosoureas (e.g., carmustine (BCNU), and lomustine (L-methyl-1-nitropropene). amoxicillin (CCNU), alkyl sulfonates (e.g., busulfan and threosulfan), triazenes (e.g., dacarbazine, temozolomide), platinum compounds (e.g., cisplatin, carboplatin, oxaliplatin), vinca alkaloids (e.g., vincristine, vinblastine, vindesine, and vinorelbine), taxanes (e.g., paclitaxel or paclitaxel equivalents, such as nanoparticle albumin-bound paclitaxel (ABRAXANE), docosahexaenoic acid-bound paclitaxel (DHA-paclitaxel, Taxoprexin), polyglutamic acid-bound paclitaxel (PG-paclitaxel, novel paclitaxel) poliglumex), CT-2103, XYOTAX), tumor-activated prodrugs (TAPs) ANG1005 (Angiopep-2 conjugated to three paclitaxel molecules), paclitaxel-EC-1 (paclitaxel conjugated to the erbB2-recognition peptide EC-1), and glucose-conjugated paclitaxel, such as 2-glucopyranosylsuccinate 2'-paclitaxel methyl ester;docetaxel, taxol), epipodophyllotoxins (e.g., etoposide, etoposide phosphate, teniposide, topotecan, 9-aminocamptothecin, captopto (irinotecan), irinotecan, crisnatol, mitomycin C), antimetabolites DHFR inhibitors (e.g., methotrexate, dichloromethotrexate, trimetrexate, edatrexate), IMP dehydrogenase inhibitors (e.g., mycophenolic acid, thiazofurine, ribavirin, and EICAR), ribonucleotide reductase inhibitors (e.g., hydroxyurea and deferoxamine), uracil analogs (e.g., 5-fluorouracil (5-FU), floxuridine, doxifluridine, raltitrexed, tegafur-uracil, capecitabine), cytosine analogs (e.g., cytarabine (ara C), cytosine arabinoside, and fludarabine), purine analogs (e.g., mercaptopurine and thioguanine), vitamin D3 analogs (e.g., EB 1089, CB1093 and KH 1060), prenylation inhibitors (e.g., lovastatin), dopaminergic neurotoxins (e.g., 1-methyl-4-phenylpyridinium), cell cycle inhibitors (e.g., staurosporine), actinomycins (e.g., actinomycin D, dactinomycin), bleomycins (e.g., bleomycin A2, bleomycin B2, peplomycin), anthracyclines (e.g., daunorubicin, doxorubicin, pegylated liposomal doxorubicin, idarubicin, epirubicin, pirarubicin, daunorubicin, mitoxantrone), MDR inhibitors (e.g., verapamil), Ca2+ ATPase inhibitors (e.g., thapsigargin), imatinib, thalidomide, lenalidomide, tyrosine kinase inhibitors (e.g., axitinib (AG013736), bosutinib (SKI-606), cediranib (RECENTIN™, AZD2171), dasatinib (; BMS-354825), erlotinib Gefitinib Imatinib ( CGP57148B, STI-571), lapatinib CEP-701, Neratinib (HKI-272), Nilotinib Semaxinib (SU5416), sunitinib ( SU11248), Tocinib Vandetanib ZD6474), vatalanib (PTK787, PTK / ZK), trastuzumab Bevacizumab Rituximab Cetuximab Panitumumab Ranibizumab Nilotinib Sorafenib Everolimus Alemtuzumab Gemtuzumab Temsirolimus ENMD-2076, PCI-32765, AC220, dovitinib lactate (TKI258, CHIR-258), BIBW2992 (TOVOKTM), SGX523, PF-04217903, PF-02341066, PF-299804, BMS-777607, ABT-869, MP470, BIBF 1120 AP24534, JNJ-26483327, MGCD265, DCC-2036, BMS-690154, CEP-11981, tivozanib (AV-951), OSI-930, MM-121, XL-184, XL-647, and / or XL228), proteasome inhibitors (e.g., bortezomib (VELCADE)), mTOR inhibitors (e.g., rapamycin, sirolimus (CCI-779), everolimus (RAD-001), rifolimus, AP23573 (Ariad), AZD8055 (AstraZeneca), BEZ235 (Novartis), BGT226 (Norvartis), XL765 (Sanofi

[00136] The invention relates to the treatment of leukemia and leukemia with the use of the following agents: Aventis), PF-4691502 (Pfizer), GDC0980 (Genetech), SF1126 (Semafoe), and OSI-027 (OSI)), oblimersen, gemcitabine, carminomycin, leucovorin, pemetrexed, cyclophosphamide, dacarbazine, procarbazine, prednisolone, dexamethasone, campathecin, plicamycin, asparaginase, aminopterin, methotrexate, porphyrin, melphalan, isovinablastine, vinblastine oxide, chlorambucil, trabectedin, procarbazine, discodermolide, carminomycin, aminopterin, and hexamethonium.

[0158] In certain embodiments, the active pharmaceutical ingredient is selected from the following group, including but not limited to: antiproliferative agents, anticancer agents, antiangiogenic agents, anti-inflammatory agents, immunosuppressants, antibacterial agents, antiviral agents, cardiovascular agents, decholesterol agents, antidiabetic agents, antiallergic agents, contraceptive agents and analgesics. In certain embodiments, the active pharmaceutical ingredient is an antiproliferative agent. In certain embodiments, the active pharmaceutical ingredient is an anticancer agent. In certain embodiments, the active pharmaceutical ingredient is an antiviral agent.

[0159] Exemplary active pharmaceutical ingredients include, but are not limited to, antibiotics, antivirals, anesthetics, anticoagulants, enzyme inhibitors, steroidal agents, steroidal or nonsteroidal anti-inflammatory agents, antihistamines, immunosuppressants, antigens, vaccines, antibodies, decongestants, sedatives, opioids, analgesics, analgesics, antipyretics, hormones, and prostaglandins, etc. Active pharmaceutical ingredients include small organic molecules such as pharmaceutical compounds (e.g., compounds approved by the US Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNA, RNA, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells.

[0160] In certain embodiments, the active pharmaceutical ingredient is an antibiotic. Exemplary antibiotics include, but are not limited to, penicillins (e.g., penicillin, amoxicillin), cephalosporins (e.g., cephalexin), macrolides (e.g., erythromycin, clarithromycin, azithromycin, troleandomycin), fluoroquinolones (e.g., ciprofloxacin, levofloxacin, ofloxacin), sulfonamides (e.g., trimethoprim), tetracyclines (e.g., tetracycline, chlortetracycline, oxytetracycline, demeclocycline, methacycline, sancycline, doxycycline, chlortetracycline, oxytetracycline, minocycline, 6-deoxytetracycline, lymecycline, meclocycline, methecycline, hydropyracycline, and glycylcycline antibiotics (e.g., tigecycline)), aminoglycosides (e.g., gentamicin, tobramycin, paromomycin), aminocyclines (e.g., spectinomycin), chloramphenicol, sparsomycin, quinupristin / dalfoprisin (Syndercid TM ). In certain embodiments, the antibiotic is a ribosome-targeting antibiotic.

[0161] In some embodiments, the active pharmaceutical ingredient is retained or encapsulated in the polymer. In some embodiments, the active pharmaceutical ingredient is retained or encapsulated on the polymer.

[0162] In some embodiments, the method is a method of increasing the residence time of an active pharmaceutical ingredient in a subject compared to when the active pharmaceutical ingredient is administered in the absence of a polymer. In some embodiments, the method is a method of increasing the residence time of an active pharmaceutical ingredient at a polymerization site in a subject compared to when the active pharmaceutical ingredient is administered in the absence of a polymer.

[0163] In some embodiments, the method is one that provides sustained release of the active pharmaceutical ingredient compared to administering the active pharmaceutical ingredient in the absence of the polymer.

[0164] In some embodiments, the method is a method of reducing the frequency of dosing of the active pharmaceutical ingredient compared to administering the active pharmaceutical ingredient in the absence of a polymer. In some embodiments, the dosing frequency is once a day. In some embodiments, the dosing frequency is twice a day.

[0165] In some embodiments, the method is a method of increasing the half-life of an active pharmaceutical ingredient compared to administering the active pharmaceutical ingredient in the absence of a polymer. In some embodiments, the method increases the half-life of an active pharmaceutical ingredient by at least about 2 times compared to administering the active pharmaceutical ingredient in the absence of a polymer. In some embodiments, the method increases the half-life of an active pharmaceutical ingredient by at least about 4 times compared to administering the active pharmaceutical ingredient in the absence of a polymer. In some embodiments, the method increases the half-life of an active pharmaceutical ingredient by at least about 6 times compared to administering the active pharmaceutical ingredient in the absence of a polymer. In some embodiments, the method increases the half-life of an active pharmaceutical ingredient by at least about 10 times compared to administering the active pharmaceutical ingredient in the absence of a polymer.

[0166] In some embodiments, the method is a method that increases the AUC of the active pharmaceutical ingredient compared to when the active pharmaceutical ingredient is administered in the absence of a polymer. In some embodiments, the method increases the AUC by at least about 2-fold compared to when the active pharmaceutical ingredient is administered in the absence of a polymer. In some embodiments, the method increases the AUC by at least about 3-fold compared to when the active pharmaceutical ingredient is administered in the absence of a polymer. In some embodiments, the method increases the AUC by at least about 4-fold compared to when the active pharmaceutical ingredient is administered in the absence of a polymer.

[0167] In some embodiments, the method is to adjust the C of the active pharmaceutical ingredient compared to administering the active pharmaceutical ingredient in the absence of the polymer. max In some embodiments, the method of regulating is increasing. In some embodiments, the method of regulating is decreasing.

[0168] In some embodiments, the method is to adjust the T of the active pharmaceutical ingredient compared to administering the active pharmaceutical ingredient in the absence of the polymer. max In some embodiments, the method of regulating is increasing. In some embodiments, the method of regulating is decreasing.

[0169] In some embodiments, the method does not affect drug metabolism once the active pharmaceutical ingredient is absorbed by the small intestine.

[0170] In some embodiments, the method is a method of treating schistosomiasis in a subject.

[0171] In some embodiments, the composition further comprises a radioprotectant. In certain embodiments, the radioprotectant is an antioxidant, a thiol-containing compound, or a nitrogen oxide. In certain embodiments, the radioprotectant is thalidomide, cysteine, amifostine, palifermin, or L-carnitine. In certain embodiments, the radioprotectant is thalidomide.

[0172] In some embodiments, the nutritional agent is vitamin D or iron.

[0173] In some embodiments, the methods provide for targeting the small intestine.

[0174] In some embodiments, the method is a method of reducing small intestinal uptake. In some embodiments, the method is a method of reducing small intestinal uptake of one or more nutrients and active pharmaceutical ingredients. In some embodiments, the method is a method of reducing small intestinal uptake of one or more nutrients. In some embodiments, the method is a method of reducing small intestinal uptake of one or more active pharmaceutical ingredients.

[0175] In some embodiments, the method is a method of increasing the residence time in the small intestine. In some embodiments, the method is a method of increasing the residence time of one or more nutrients and active pharmaceutical ingredients in the small intestine. In some embodiments, the method is a method of increasing the residence time of one or more nutrients in the small intestine. In some embodiments, the method is a method of increasing the residence time of one or more active pharmaceutical ingredients in the small intestine.

[0176] In some embodiments, the method maintains the intestinal lumen distended.

[0177] In some embodiments, the method is a method of treating or preventing intestinal adhesions in a subject. In some embodiments, the method is a method of preventing intestinal adhesions in a subject.

[0178] In some embodiments, the method is a method of treating or preventing intestinal obstruction in a subject. In some embodiments, the method is a method of preventing intestinal obstruction in a subject.

[0179] In some embodiments, the method is a method of treating bleeding in a subject. In some embodiments, the method is a method of treating small intestinal bleeding in a subject. In some embodiments, the bleeding is in the upper GI tract. In some embodiments, the bleeding is in the stomach. In some embodiments, the method of treating bleeding is a method of treating hemostasis.

[0180] In some embodiments, the polymer regulates absorption in the small intestine. In some embodiments, the polymer regulates absorption of one or more nutrients or active pharmaceutical ingredients, or a combination thereof, in the small intestine. In some embodiments, the polymer regulates absorption of one or more nutrients and active pharmaceutical ingredients in the small intestine. In some embodiments, the polymer regulates absorption of one or more nutrients in the small intestine. In some embodiments, the polymer regulates absorption of one or more active pharmaceutical ingredients in the small intestine.

[0181] In some embodiments, the polymer modulates digestion in the small intestine. In some embodiments, the polymer modulates digestion of one or more nutrients in the small intestine.

[0182] In certain embodiments, the polymer substantially blocks absorption in the small intestine. In some embodiments, the polymer substantially blocks absorption of one or more nutrients or active pharmaceutical ingredients, or a combination thereof, into the epithelium on which the polymer is formed. In some embodiments, the polymer substantially blocks absorption of one or more nutrients into the epithelium on which the polymer is formed. In some embodiments, the polymer substantially blocks absorption of one or more active pharmaceutical ingredients into the epithelium on which the polymer is formed.

[0183] In some embodiments, the polymer substantially blocks the absorption of one or more nutrients or active pharmaceutical ingredients, or a combination thereof, into the intestinal wall of a subject. In some embodiments, the polymer substantially blocks the absorption of one or more nutrients into the intestinal wall of a subject. In some embodiments, the polymer substantially blocks the absorption of one or more active pharmaceutical ingredients into the intestinal wall of a subject.

[0184] In some embodiments, the polymer substantially blocks the absorption of one or more nutrients or active pharmaceutical ingredients, or a combination thereof, into the bloodstream of a subject. In some embodiments, the polymer substantially blocks the absorption of one or more nutrients into the bloodstream of a subject. In some embodiments, the polymer substantially blocks the absorption of one or more active pharmaceutical ingredients into the bloodstream of a subject.

[0185] In some embodiments, the method is a method of immobilizing an enzyme in a subject.

[0186] In some embodiments, the method is a method of delivering an active pharmaceutical ingredient to a subject.

[0187] In some embodiments, the method is a method of supplementing digestion in a subject.

[0188] In some embodiments, the polymer induces blood gelation. In certain embodiments, the polymer induces blood coagulation. In some embodiments, the composition is in the form of a powder. In certain embodiments, the method comprises spraying the powder onto the affected area on or in the subject.

[0189] In some embodiments, the polymer is non-toxic. In some embodiments, the composition is non-toxic. In some embodiments, the composition and its components are non-toxic.

[0190] In some embodiments, polymer is stable to physical and chemical forces. In some embodiments, polymer is stable to one or more of intestinal fluid, intestinal acid, gastric acid, chyme, ethanol and saline. In some embodiments, polymer is decomposed less than about 25% when exposed to one or more of intestinal fluid, intestinal acid, gastric acid, chyme, ethanol or saline. In some embodiments, polymer is decomposed less than about 20% when exposed to one or more of intestinal fluid, intestinal acid, gastric acid, chyme, ethanol or saline. In some embodiments, polymer is decomposed less than about 10% when exposed to one or more of intestinal fluid, intestinal acid, gastric acid, chyme, ethanol or saline. In some embodiments, polymer is decomposed less than about 5% when exposed to one or more of intestinal fluid, intestinal acid, gastric acid, chyme, ethanol or saline. In some embodiments, physical forces are selected from one or more of peristalsis and segmentation.

[0191] In another aspect, the present disclosure provides a method of treating a disease or disorder, the method comprising administering to a subject in need thereof an effective amount of a composition as described herein.

[0192] The present disclosure also provides a method of preventing a disease or disorder, the method comprising administering to a subject in need thereof an effective amount of a composition as described herein.

[0193] In some embodiments, the disease or disorder is a metabolic disorder, an eye disease, a systemic disease, a digestive disorder, an infectious disease, a cancer, a hemorrhage, an ulcer, an intestinal obstruction, a mesenteric ischemia, an obesity, a mental disorder, an Alzheimer's disease, or a transplant rejection. In some embodiments, the disease or disorder is a metabolic disorder, a systemic disease, a digestive disorder, an infectious disease, a cancer, a hemorrhage, an ulcer, an intestinal obstruction, a mesenteric ischemia, an obesity, a mental disorder, an Alzheimer's disease, or a transplant rejection.

[0194] In some embodiments, the disease is cancer. Exemplary cancers include, but are not limited to, acoustic neuroma; adenocarcinoma; adrenal cancer; anal cancer; angiosarcoma (e.g., lymphangiosarcoma, lymphangioendothelioma, hemangiosarcoma); appendix cancer; benign monoclonal gammopathy; bile duct cancer (e.g., cholangiocarcinoma); bladder cancer; breast cancer (e.g., breast adenocarcinoma, breast papillary carcinoma, breast cancer, medullary breast cancer); brain cancer (e.g., meningioma, glioblastoma, glioma (e.g., astrocytoma, oligodendroglioma), neuroblastoma endothelial sarcoma (eg, Kaposi sarcoma, multiple idiopathic hemorrhagic sarcomas); endometrial cancer (eg, uterine cancer, uterine sarcoma); esophageal cancer (eg, esophageal adenocarcinoma, Barrett's adenocarcinoma); Ewing's sarcoma; eye cancer (eg, intraocular melanoma, retinoblastoma); common eosinophilia; gallbladder cancer; gastric cancer (eg, gastric adenocarcinoma); gastrointestinal stromal tumor (GIST) ; germ cell cancer; head and neck cancer (e.g., head and neck squamous cell carcinoma, oral cancer (e.g., oral squamous cell carcinoma), throat cancer (e.g., laryngeal cancer, pharyngeal cancer, nasopharyngeal cancer, oropharyngeal cancer)); hematopoietic cancer (e.g., leukemias such as acute lymphocytic leukemia (ALL) (e.g., B-cell ALL, T-cell ALL), acute myeloid leukemia (AML) (e.g., B-cell AML, T-cell AML), chronic myeloid leukemia (CML) (e.g., B-cell CML, T-cell CML) and chronic lymphocytic leukemia (CLL) (e.g., B-cell CLL, T-cell CLL)); lymphomas such as Hodgkin's disease Hodgkin lymphoma (HL) (e.g., B-cell HL, T-cell HL) and non-Hodgkin lymphoma (NHL) (e.g., B-cell NHL such as diffuse large cell lymphoma (DLCL) (e.g., diffuse large B-cell lymphoma), follicular lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), mantle cell lymphoma (MCL), marginal zone B-cell lymphoma (e.g., mucosa-associated lymphoid tissue (MALT) lymphoma, nodal marginal zone B-cell lymphoma, splenic marginal zone B-cell lymphoma), primary mediastinal B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma (i.e., Waldenstrom's disease) macroglobulinemia), hairy cell leukemia (HCL), immunoblastic large cell lymphoma, B precursor lymphoblastic lymphoma, and primary central nervous system (CNS) lymphoma; and T-cell NHL such as T precursor lymphoblastic lymphoma / leukemia, peripheral T-cell lymphoma (PTCL) (e.g., cutaneous T-cell lymphoma (CTCL) (e.g., mycosis fungoides, Sezary syndrome), angioimmunoblastic T-cell lymphoma, extranodal natural killer T-cell lymphoma, enteropathy-type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and anaplastic large cell lymphoma); mixed conditions of one or more of the leukemia / lymphomas described above; and multiple myeloma (MM)), heavy chain disease (e.g. (e.g., α-chain disease, γ-chain disease, μ-chain disease); hemangioblastoma; hypopharyngeal cancer; inflammatory myofibroblastic tumor; immune cell amyloidosis; kidney cancer (e.g., Wilms' tumor, renal cell carcinoma); liver cancer (e.g., hepatocellular carcinoma (HCC), malignant hepatoma); lung cancer (e.g., bronchogenic carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), lung adenocarcinoma); leiomyosarcoma (LMS); mastocytosis (e.g., systemic mastocytosis); muscle cancer; myelodysplastic syndrome (MDS); mesothelioma; myeloproliferative disorders (MPD) (e.g., polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myeloid metaplasia (AMM, also known as myelofibrosis (MF), chronic idiopathic myelofibrosis, chronic myelocytic leukemia (CML), chronic neutrophilic leukemia (CNL), hypereosinophilic syndrome (HES)); neuroblastoma; neurofibroma (e.g., neurofibromatosis type 1 or type 2, schwannomatosis); neuroendocrine cancer (e.g., gastroenteropancreatic neuroendocrine tumor (GEP-NET), carcinoid tumor); osteosarcoma (e.g., bone cancer); ovarian cancer (e.g., cystadenocarcinoma, ovarian embryonal carcinoma, ovarian adenocarcinoma); papillary adenocarcinoma; pancreatic cancer (e.g., pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), islet cell tumor); Penile cancer (e.g., Paget's disease of the penis and scrotum); pinealoma; primitive neuroectodermal tumor (PNT); plasma cell neoplasia; paraneoplastic syndrome; intraepithelial neoplasia; prostate cancer (e.g., prostate adenocarcinoma); rectal cancer; rhabdomyosarcoma; salivary gland cancer; skin cancer (e.g., squamous cell carcinoma (SCC), keratoacanthoma (KA), melanoma, basal cell carcinoma (BCC)); small intestine cancer (e.g., appendix cancer); soft tissue sarcomas (e.g., malignant fibrous histiocytoma (MFH), liposarcoma, malignant peripheral nerve sheath tumor (MPNST), chondrosarcoma, fibrosarcoma, myxosarcoma); sebaceous gland carcinoma; small intestine cancer; sweat adenoma; synovioma; testicular cancer (e.g., seminoma, testicular embryonal carcinoma);Thyroid cancer (e.g., papillary thyroid carcinoma, papillary thyroid carcinoma (PTC), medullary thyroid carcinoma); urethral cancer; vaginal cancer; and vulvar cancer (e.g., Paget's disease of the vulva).

[0195] In some embodiments, the metabolic disorder is hyperinsulinemia.

[0196] In some embodiments, the digestive disease is Crohn's disease, ulcerative colitis, malabsorption, inflammatory bowel disease, irritable bowel syndrome, lactose intolerance, or celiac disease. In some embodiments, the disease is Crohn's disease.

[0197] In some embodiments, the disease is a psychiatric disorder.

[0198] In some embodiments, the disease is Alzheimer's disease.

[0199] In some embodiments, the disorder is transplant rejection.

[0200] In some embodiments, the systemic disease is an autoimmune disease. Exemplary autoimmune diseases include, but are not limited to, glomerulonephritis, Goodpasture's syndrome, necrotizing vasculitis, lymphadenitis, periarteritis nodosa, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, psoriasis, ulcerative colitis, systemic sclerosis, dermatomyositis / polymyositis, antiphospholipid antibody syndrome, scleroderma, pemphigus vulgaris, ANCA-associated vasculitis (e.g., Wegener's granulomatosis, microscopic polyangiitis), uveitis, Sjogren's syndrome, Crohn's disease, Reiter's syndrome, ankylosing spondylitis, Lyme disease, Guillain-Barré syndrome, Hashimoto's thyroiditis, and cardiomyopathy.

[0201] In some embodiments, the systemic disease is mastocytosis, chronic fatigue syndrome, systemic vasculitis, sarcoidosis, hypothyroidism, diabetes, fibromyalgia, adrenal insufficiency, celiac disease, ulcerative colitis, Crohn's disease, hypertension, metabolic syndrome, AIDS, Graves' disease, systemic lupus erythematosus, arthritis, atherosclerosis, sickle cell disease, myasthenia gravis, systemic sclerosis, an inflammatory disease, or sinusitis.

[0202] In some embodiments, the disease is an inflammatory disease. Inflammatory diseases include, but are not limited to, atherosclerosis, arteriosclerosis, autoimmune disorders, multiple sclerosis, systemic lupus erythematosus, polymyalgia rheumatica (PMR), gouty arthritis, degenerative arthritis, tendinitis, bursitis, psoriasis, cystic fibrosis, osteoarthritis, rheumatoid arthritis, inflammatory arthritis, Sjögren's syndrome, giant cell arteritis, progressive systemic sclerosis (scleroderma), ankylosing spondylitis, polymyositis, dermatomyositis, pemphigus, pemphigoid, diabetes (e.g., type I), myasthenia gravis, Hashimoto's thyroiditis, Graves' disease, Goodpasture's disease, Mixed connective tissue disease, sclerosing cholangitis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, pernicious anemia, inflammatory skin diseases, usual interstitial pneumonia (UIP), asbestosis, silicosis, bronchiectasis, berylliosis, talcosis, pneumoconiosis, sarcoidosis, desquamative interstitial pneumonia, lymphointerstitial pneumonia, giant cell interstitial pneumonia, cellular interstitial pneumonia, extrinsic allergic alveolitis, Wegener's granulomatosis and related forms of vasculitis (temporal arteritis and polyarteritis nodosa), inflammatory skin diseases, hepatitis, delayed allergic reactions (e.g., poison ivy dermatitis), lung inflammation, respiratory inflammation, adult respiratory distress syndrome (ARDS), encephalitis, immediate hypersensitivity reaction, asthma, hay fever, allergy, acute allergic reaction, rheumatic fever, glomerulonephritis, pyelonephritis, cellulitis, cystitis, chronic cholecystitis, ischemia (ischemic injury), reperfusion injury, allograft rejection, host-versus-graft reaction, appendicitis, arteritis, blepharitis, bronchiolitis, bronchitis, cervicitis, cholangitis, chorioamnionitis, conjunctivitis, dacryoadenitis, dermatomyositis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis Inflammatory diseases of the eye include, but are not limited to, postoperative inflammation. In some embodiments, the disease is an inflammatory joint disease. In some embodiments, the disease is arthritis. In certain embodiments, the disease is osteoarthritis. In some embodiments, the disease is rheumatoid arthritis. In some embodiments, the disease is rheumatoid arthritis. In some embodiments, the disease is osteoarthritis. In some embodiments, the disease is rheumatoid arthritis.

[0203] In some embodiments, the disease is obesity, hyperinsulinemia, or diabetes. In some embodiments, the disease is obesity. In some embodiments, the disease is hyperinsulinemia. In some embodiments, the disease is diabetes. In some embodiments, the disease is type 2 diabetes.

[0204] In some embodiments, the disease is an infectious disease. In some embodiments, the disease is a bacterial, viral, fungal, or parasitic infection. In some embodiments, the disease is a parasitic disease. In some embodiments, the disease is giardiasis, ascariasis, or a tapeworm infection. In some embodiments, the disease is schistosomiasis. In some embodiments, the disease is a viral infection. In some embodiments, the disease is influenza.

[0205] In some embodiments, the disease is lactose intolerance.

[0206] In some embodiments, the disorder is intestinal obstruction. In some embodiments, the disorder is intestinal adhesion. In certain embodiments, the methods and compositions described herein prevent re-adhesion and / or re-obstruction of the intestine.

[0207] In certain embodiments, the methods and compositions provided herein are contraceptives.

[0208] In certain embodiments, the disease is trauma.

[0209] In some embodiments, the present disclosure provides use of a composition for forming a polymer in vivo, the use comprising administering to a subject a composition comprising a monomer and an oxygen source, wherein the monomer and the oxygen source contact a catalyst endogenous to the subject in vivo and the catalyst polymerizes the monomer in situ, wherein the monomer is dopamine or a salt thereof.

[0210] In another aspect, the present disclosure provides use of a composition for forming a polymer in vivo, the use comprising administering to a subject a composition comprising a monomer and an oxygen source, wherein the monomer and oxygen source contact a catalyst endogenous to the subject in vivo and the catalyst polymerizes the monomer in situ, and wherein the monomer is dopamine or a salt thereof, the oxygen source is hydrogen peroxide or urea hydrogen peroxide, and the endogenous catalyst is selected from catalase or peroxidase.

[0211] In one aspect, the present disclosure provides for use of an effective amount of a composition as described herein for treating a disease or disorder in a subject in need thereof.

[0212] In another aspect, the present disclosure provides use of an effective amount of a composition as described herein for preventing a disease or disorder in a subject in need thereof.

[0213] Composition

[0214] In certain aspects, also provided herein are compositions comprising dopamine, an oxygen source, and optionally a buffer.

[0215] In some embodiments, the composition comprises about 0.001 to about 1000 mg / mL of dopamine, about 0.01 to about 100 mM of an oxygen source, and optionally a buffer.

[0216] In some embodiments, the composition comprises about 0.001 to about 1000 mg / mL of dopamine. In some embodiments, the composition comprises about 0.001 to about 500 mg / mL of dopamine. In some embodiments, the composition comprises about 0.01 to about 100 mg / mL of dopamine. In some embodiments, the composition comprises about 1 to about 20 mg / mL of dopamine. In some embodiments, the composition comprises about 10 mg / mL of dopamine. In some embodiments, the composition comprises about 9.8 mg / mL of dopamine.

[0217] In some embodiments, the composition comprises about 0.01 to about 100 mM of an oxygen source. In some embodiments, the composition comprises about 0.1 to about 50 mM of an oxygen source. In some embodiments, the composition comprises about 1 to about 30 mM of an oxygen source. In some embodiments, the composition comprises about 20 mM of an oxygen source. In some embodiments, the composition comprises an oxygen source at a concentration compatible with the subject's uptake.

[0218] In some embodiments, the composition has a pH of about 7 to about 10. In some embodiments, the composition has a pH of about 7 to about 9. In some embodiments, the composition has a pH of about 8.5. In some embodiments, the composition has a pH of about 7.4.

[0219] In some embodiments, the composition comprises about 10 mg / mL of dopamine, about 20 mM of hydrogen peroxide or urea hydrogen peroxide, and optionally a buffer. In some embodiments, the composition comprises about 9.8 mg / mL of dopamine, about 20 mM of hydrogen peroxide or urea hydrogen peroxide, and optionally a buffer.

[0220] In some embodiments, the buffer comprises phosphate, acetate, citrate, N-[tris(hydroxymethyl)methyl]glycine), (tris(hydroxymethyl)aminomethane), or (2-(bis(2-hydroxyethyl)amino)acetic acid). In some embodiments, the buffer comprises tris(hydroxymethyl)aminomethane.

[0221] In some embodiments, the composition further comprises a digestive enzyme, a nutrient blocker, a radioprotectant, a nutraceutical, an active pharmaceutical ingredient, a diagnostic agent, or a combination thereof.

[0222] In some embodiments, the composition is a liquid or solid dosage form. In some embodiments, the composition is in the form of a solution, gel, tablet, or capsule.

[0223] Reagent test kit

[0224] The present disclosure also encompasses kits (eg, pharmaceutical packages). The provided kits can include a composition described herein and a container (eg, a vial, ampoule, bottle, syringe and / or dispenser package, or other suitable container).

[0225] The present disclosure also provides a kit. In one aspect, the present disclosure provides a kit comprising: a composition as described herein, and instructions for administering the composition to a subject. In some embodiments, the composition comprises: dopamine; hydrogen peroxide or urea hydrogen peroxide; a buffer; and optional enzymes, nutrient blockers, radiation protectors, nutritional preparations, active pharmaceutical ingredients, diagnostic agents, or combinations thereof. In some embodiments, the buffer is tris (hydroxymethyl) aminomethane. In certain embodiments, the kit also comprises an endoscope, an arthroscope, a cystoscope, a colposcope, a colonoscope, a bronchoscope, a ureteroscope, an anoscope, an esophagoscope, a gastroscope, a laparoscope, a laryngoscope, a neuroendoscope, a proctoscopy, a sigmoidoscope, or a thoracoscope. In certain embodiments, the composition is in the form of a capsule.

[0226] In some embodiments, the kits provided may also optionally include a second container comprising a pharmaceutical excipient for diluting or suspending the composition described herein. In some embodiments, the composition described herein provided in the first container and the second container are combined to form a unit dosage form.

[0227] Thus, in one aspect, a kit is provided, the kit comprising a first container comprising a composition as described herein. In certain embodiments, the kit can be used to treat a disease in a subject in need thereof. In certain embodiments, the kit can be used to prevent a disease in a subject in need thereof. In certain embodiments, the kit can be used to reduce the risk of developing a disease in a subject in need thereof.

[0228] In certain embodiments, kits as described herein also include instructions for use of the kit. Kits as described herein may also include information as required by regulatory agencies such as the U.S. Food and Drug Administration (US Food and Drug Administration) (FDA). In certain embodiments, the information included in the kit is prescription information. In certain embodiments, the kit and instructions provide for treating diseases in subjects in need. In certain embodiments, the kit and instructions provide for preventing diseases in subjects in need. In certain embodiments, the kit and instructions provide for reducing the risk of developing diseases in subjects in need. Kits as described herein may include one or more additional agents as described herein as separate compositions.

[0229] Drug administration

[0230] The methods and uses described herein comprise administering to a subject an effective amount of a composition comprising a monomer and an oxygen source (ie, to form a polymer in situ (eg, to treat or prevent a disease)).

[0231] In some embodiments, the composition is administered orally. In some embodiments, the composition is a liquid or solid dosage form. In some embodiments, the composition is in the form of a solution, gel, tablet, or capsule.

[0232] In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is an amount for effectively treating infectious diseases in a subject in need thereof. In certain embodiments, the effective amount is an amount for effectively preventing infectious diseases in a subject in need thereof. In certain embodiments, the effective amount is a preventive effective amount. In certain embodiments, the effective amount is an amount for effectively treating proliferative diseases in a subject in need thereof. In certain embodiments, the effective amount is an amount for effectively preventing proliferative diseases in a subject in need thereof. In certain embodiments, the effective amount is an amount for effectively treating blood diseases in a subject in need thereof. In certain embodiments, the effective amount is an amount for effectively preventing blood diseases in a subject in need thereof. In certain embodiments, the effective amount is an amount for effectively treating neurological diseases in a subject in need thereof. In certain embodiments, the effective amount is an amount for effectively preventing neurological diseases in a subject in need thereof. In certain embodiments, the effective amount is an amount for effectively treating pain conditions in a subject in need thereof. In certain embodiments, the effective amount is an amount for effectively preventing pain conditions in a subject in need thereof. In certain embodiments, the effective amount is an amount for effectively treating mental disorders in a subject in need thereof. In certain embodiments, an effective amount is the amount of effectively preventing mental disorders in a subject in need. In certain embodiments, an effective amount is the amount of effectively treating metabolic disorders in a subject in need. In certain embodiments, an effective amount is the amount of effectively preventing metabolic disorders in a subject in need. In certain embodiments, an effective amount is the amount of reducing the risk of developing a disease (e.g., infectious diseases, proliferative diseases, hematological diseases, neurological diseases, pain disorders, mental disorders, or metabolic disorders) in a subject in need. In certain embodiments, an effective amount is the amount of effectively suppressing the activity (e.g., abnormal activity, such as increased activity) of an organism in a subject or cell.

[0233] In certain embodiments, the subject is an animal. The animal can be of either sex and can be at any stage of development. In certain embodiments, the subject described herein is a human being. In some embodiments, the subject is an adult. In certain embodiments, the subject is a child. In certain embodiments, the subject is a non-human animal. In certain embodiments, the subject is a mammal. In certain embodiments, the subject is a non-human mammal. In certain embodiments, the subject is a domesticated animal, such as a dog, cat, cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a companion animal, such as a dog or cat. In certain embodiments, the subject is a livestock animal, such as a cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a zoo animal. In another embodiment, the subject is a research animal, such as a rodent (e.g., mouse, rat), dog, pig, or non-human primate. In certain embodiments, the animal is a genetically engineered animal. In certain embodiments, the animal is a transgenic animal (e.g., transgenic mouse and transgenic pig). In certain embodiments, the subject is a fish or a reptile.

[0234] The composition can be prepared, packaged and / or sold in bulk as a single unit dose and / or as multiple single unit doses. A "unit dose" is a discrete amount of a composition containing a predetermined amount of an agent or active ingredient. The amount of an agent or active ingredient is generally equal to the dose of the agent or active ingredient to be administered to a subject, and / or a convenient portion of such a dose, such as one-half or one-third of such a dose.

[0235] Although the descriptions of compositions provided herein are primarily directed to compositions suitable for administration to humans, the skilled artisan will appreciate that such compositions are generally suitable for administration to animals of all kinds. Modifications of compositions suitable for administration to humans to make the compositions suitable for administration to various animals are well known, and an ordinary skilled veterinary pharmacologist can design and / or perform such modifications with ordinary experimentation.

[0236] The compositions provided herein are typically formulated in unit dosage form for ease of administration and uniformity of dosage. However, it should be understood that the total daily dosage of the compositions described herein will be determined by the physician within the scope of reasonable medical judgment. The specific therapeutically effective dosage level for any particular subject or organism will depend on a variety of factors, including the severity of the disease being treated and the disorder; the activity of the specific agent or active ingredient used; the specific composition used; the age, weight, general health, sex and diet of the subject; the administration time, route of administration and excretion rate of the specific agent or active ingredient used; the duration of treatment; the drugs used in combination or simultaneously with the specific agent or active ingredient used; and similar factors known in the medical field.

[0237] The compositions provided herein can be administered by any route, including enteral (e.g., oral), parenteral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, intradermal (interdermal), rectal, ocular, intravaginal, intraperitoneal, topical, mucosal, nasal, buccal, sublingual; by tracheal instillation, bronchial instillation and / or inhalation; and / or as oral spray, nasal spray and / or aerosol. In addition, the intended route is to be directly applied to the affected site. In general, the most appropriate route of administration will depend on a variety of factors, including the nature of the reagent (e.g., its stability in the gastrointestinal environment) and / or the condition of the subject (e.g., whether the subject can tolerate oral administration). In some embodiments, the route of administration is local (to the skin, eye, ear, mouth, or affected site).

[0238] The exact amount of the reagent or active ingredient required for achieving an effective amount will vary from subject to subject, depending on, for example, the species, age and general condition of the subject, the severity of the side effect or obstacle, the identification of the specific reagent or active ingredient, the mode of administration, etc. The effective amount may be included in a single dose (e.g., a single oral dose) or multiple doses (e.g., multiple oral doses). In certain embodiments, when multiple doses are applied to a subject or applied to a tissue or cell, any two doses in the multiple doses include different or substantially the same amount of reagents or active ingredients as described herein. In certain embodiments, when multiple doses are applied to a subject or applied to a tissue or cell, the frequency of applying multiple doses to a subject or applying multiple doses to a tissue or cell is three doses per day, two doses per day, one dose per day, one dose every other day, one dose every three days, one dose per week, one dose every two weeks, one dose every three weeks, or one dose every four weeks. In certain embodiments, applying multiple doses to a subject or applying multiple doses to a tissue or cell is one dose per day. In certain embodiments, applying multiple doses to a subject or applying multiple doses to a tissue or cell is two doses per day. In certain embodiments, the frequency of applying multiple doses to a subject or applying multiple doses to a tissue or cell is three doses per day. In certain embodiments, when multiple doses are applied to a subject or applied to a tissue or cell, the duration between the first dose of multiple doses and the last dose is one day, two days, four days, one week, two weeks, three weeks, one month, two months, three months, four months, six months, nine months, one year, two years, three years, four years, five years, seven years, ten years, fifteen years, twenty years or the life span of a subject, a tissue or a cell. In certain embodiments, the duration between the first dose of multiple doses and the last dose is three months, six months, or one year. In certain embodiments, the duration between the first dose of multiple doses and the last dose is the life span of a subject, a tissue or a cell.

[0239] Compositions as described herein can be administered in combination with one or more additional agents (e.g., therapeutic and / or preventive active agents). Compositions can be administered in combination with additional agents that improve their activity (e.g., treating diseases in subjects in need, preventing diseases in subjects in need, reducing the risk of developing diseases in subjects in need, and / or suppressing the activity of organisms in subjects or cells (e.g., efficacy and / or efficacy)), improve bioavailability, improve safety, reduce drug resistance, reduce and / or change metabolism, inhibit excretion, and / or change distribution in subjects or cells. It should also be understood that the therapy used can achieve the desired effect for the same obstacle, and / or it can achieve different effects.

[0240] The compositions can be administered simultaneously with, prior to, or after one or more additional agents, which can be used, for example, as a combination therapy. Example

[0241] In order that the invention described herein may be more fully understood, the following examples are set forth.The examples described in this application are provided to illustrate the compounds, compositions and methods provided herein and are not to be construed in any way as limiting the scope thereof.

[0242] abbreviation

[0243] PDA: Polydopamine

[0244] CAT: Catalase

[0245] GSEL: Gastrointestinal synthetic epithelial layer

[0246] PBS: Phosphate buffered saline

[0247] TBS: Tris buffered saline

[0248] TBST: Tris-buffered saline containing TritonX 100

[0249] IgG: Immunoglobulin G

[0250] mRNA: messenger ribonucleic acid

[0251] cDNA: complementary deoxyribonucleic acid

[0252] FTIR: Fourier Transform Infrared

[0253] Chemicals and Materials

[0254] Dopamine hydrochloride (1225204), simulated gastric fluid (18818), urea H2O2 (289132), catalase (C3556 & C1345), Triton X-100 (T8787), 3-amino-1,2,4-triazole (A8056), RIPA buffer (R0278), protease inhibitor cocktail (P8340), phosphatase inhibitor cocktail 3 (P0044), Trizma base, o-nitrophenol-β-D-galactoside (N1127), β-galactosidase (1356698), glucose (G8270) and lactose (17814) were purchased from Sigma-Aldrich. Formalin (10%, phosphate buffered saline) (SF100), Tissue-Plus OCT (23-730-571), BD GasPak EZ Gas Generation System Incubation Container (B260002), and SouthernBiotech Fluoromount-G Slide Mounting Medium (OB100) were purchased from Fisher Scientific. Pierce BCA protein assay (23225), Pierce DAB substrate (34002), Pierce 16% formaldehyde (w / v) (28908), rabbit anti-goat immunoglobulin G (IgG) (H+L) secondary antibody-HRP (31402), goat anti-rabbit IgG (H+L) secondary antibody-HRP (65-6120), Vybrant MTT cell viability assay (V13154), Dynabeads M-280 (tosyl activated) (14203), SeeBlue Plus2 prestained protein standard (LC5925), SuperSignal West FemtoMaximum Sensitivity substrate (34094), Pierce ECL Western Blotting Substrate (32109), NuPAGE 4-12% Bis-Tris protein gel (NP0321BOX), NE-PER nuclear and cytoplasmic extraction kit (78835), Mem-PERplus membrane protein extraction kit (89842), antibiotic-antimycotic (100X) (15240062), SuperScript IV reverse transcriptase (18090050), PCR Master Mix and all primers were purchased from ThermoFisher. Total RNA isolation kit was purchased from ZYMO RESEARCH. Precision Plus Protein dual color standard (#1610374) was purchased from Bio-Rad. Barium sulfate (13989) was purchased from Alfa Aesar. Simulated intestinal fluid was purchased from VWR.CYP3A4 activity assay kit (ab211076), calcium assay kit (ab102505), glutamate assay kit (ab138883), anti-catalase and anti-β-actin antibodies were purchased from Abcam. Catalase (CAT) assay kit (E-BC-K031) was purchased from Elabscience. Praziquantel was purchased from ArkPharm. Sieve (150 and 300 μm mesh size) was purchased from McMaster-Carr. Glo-Tip spray tube (G24892) was purchased from COOKMedical. All other chemicals and biochemicals (unless otherwise stated) were purchased from Sigma-Aldrich and used without further purification.

[0255] method

[0256] General Principles. In vivo tissue accelerated polymerization coating performance was evaluated in a large animal (porcine) model of the GI tract by multiple techniques including endoscopy, intestinal ligation, and X-ray imaging. Yorkshire pigs (45-55 kg) were chosen as a model given their anatomical and genomic similarities to the human digestive system. Biocompatibility was characterized according to OECD guidelines. All animal experiments were approved by and performed in accordance with the Committee on Animal Care of the Massachusetts Institute of Technology. 19,28 The groups and sample sizes for each experiment are indicated in the figure descriptions. Independent experiments for each sample were performed on different animals. All rats were randomized into different experimental groups, but because pigs were only used on demand, no randomization plan was pre-established for the in vivo pig studies.

[0257] Preparation of tissue-accelerating polymerization solution. Dopamine hydrochloride powder (500 mg) was quickly dissolved in Tris buffer (50 mM, 50 ml) at pH 8.5, and then H2O2 (1 M, 1 ml) was quickly added. The mixed Tris-buffered tissue-accelerating polymerization solution was used freshly. Unless otherwise specified, the mixed solution was used freshly in all experiments and was referred to as tissue-accelerating polymerization solution, etc., and gastrointestinal synthetic epithelial layer (GSEL). Tissue-accelerating polymerization capsules were prepared using solid urea H2O2 (as a substitute for H2O2 solution). Capsules were prepared with dopamine hydrochloride powder (500 mg), Tris powder (30-300 mg; for example, 300 mg) and solid urea H2O2 powder (10-50 mg; for example, 50 mg). The mixed powder was filled into (000) capsules (see Fig.37 ).

[0258] In vitro evaluation of catalase-catalyzed polymerization of polydopamine. Tissue-accelerated polymerization solution (200 μl) was first prepared and added to a 96-well plate, followed by the addition of catalase (1 mg / mL, 5 μl in 1X phosphate-buffered saline (PBS) buffer). All solutions were placed in a container with low oxygen partial pressure (BD GasPak EZ). The reaction mixture was maintained at 37°C for 10-130 minutes. The extinction of the solution at 700 nm was measured using an Infinite M200 plate reader (Tecan). The results were compared with those obtained from solutions to which no catalase and H2O2 were added and with those obtained from reactions under conventional conditions (in air). See Figure 1 C to 1D and 6A to 6B.

[0259] Characterization of polydopamine using FTIR and UV-Vis spectroscopy. Polydopamine standards were prepared by polymerizing dopamine solutions (10 mg / mL) under conventional conditions (in air) for 24 hours (H. Lee, SM Dellatore, WM Miller, PB Messersmith, Mussel-inspired surface chemistry for multifunctional coatings., Science 318, 426–30 (2007)). For catalase-catalyzed polydopamine, catalase (1 mg / mL) was placed in a dialysis device (5 ml), which was combined with tissue accelerated polymerization solution (100 ml) for 24 hours. After the reaction, the polydopamine solution was measured by FTIR (Nicolet) and UV-Vis spectroscopy (Varian Cary 100). See Figure 7 A to 7D and 8A to 8C.

[0260] In vitro evaluation of tissue accelerated polymerization coating performance. Porcine tissue was obtained from Blood Farm Slaughterhouse (West Groton, USA). The pigs were euthanized and fresh tissue was excised and stored on ice. Human tissue specimens were obtained from 4 donors of different age, race, and gender (National Disease Research Interchange, NDRI, USA). Tissue (12 cm 2) were exposed to tissue accelerated polymerization solution (10 mL) and washed 3 times with PBS buffer (1X) to remove excess polydopamine. Samples (6 mm in diameter) were collected at 3-5 random sites of the polydopamine-coated tissue, and images of the samples were analyzed to quantify polydopamine coating. Regions of interest including polydopamine-coated tissue and excluding "blank" tissue-free areas were identified using ImageJ. The same analysis was performed on all samples in each group to obtain the overall average polydopamine signal intensity and evaluate signal changes. The tissue was exposed to antibiotic-antimycotic solution (10X, Gibco) and washed 3 times with PBS buffer (1X) to remove bacteria in the mucus. The villi were peeled off from the luminal surface of the small intestinal tissue (opened longitudinally) placed on an ice-cold matrix. Cell fractionation of the villi was performed using a cytoplasm and membrane extraction kit (NE-PER, Mem-PER) based on the kit's protocol. CYP3A4 activity was measured by CYP3A4 activity assay (Abcam) based on the assay protocol. See Figure 1 E to 1H, 5A to 5G, 9, 13, 15, 24, 25, 27, 28, 32, 34 and 35.

[0261] Preparation of tissue lysates. Epithelial tissues of the porcine gastrointestinal tract were dissected on ice. The outer mucus layer was removed by aspiration, and the rinsed tissues were then frozen by liquid nitrogen [(with 1X phosphate buffered saline (PBS)]. Tissues (10 mg) were incubated and homogenized in ice-cold lysis buffer (600 μl, RIPA buffer mixed with a cocktail of protease and phosphatase inhibitors, Sigma-Aldrich) to form tissue lysates. The total protein concentration of tissue lysates was measured using the bicinchoninic acid (BCA) assay.

[0262] Catalytic Capacity Analysis of Tissue Lysates. A non-denaturing gel-based catalytic activity assay was performed. Proteins in tissue lysates were separated on a 7.5% non-denaturing polyacrylamide gel and the gel was stained with Gastrointestinal Synthetic Epithelial Layer (Tissue Accelerated Polymerization) solution (50 ml) for 10 minutes. After staining, the gel was washed 3 times with PBS buffer (1X) and imaged. See Figure 2 Ace and 10.

[0263] In vitro inhibition of catalase activity. 3-Amino-1,2,4-triazole was used as an inhibitor. Tissue lysates (10 mg / ml, 100 μl) were incubated in inhibitor solution (20 mM) at 4°C for 6 hours. Figure 2 B.

[0264] Immunoprecipitation of catalase in tissue lysates. First, catalase antibodies were conjugated to tosyl-activated magnetic beads (Dynabeads M-280) based on the immunomagnetic beads (Dynabeads) protocol. The conjugated beads (60 mg) were further added to the tissue lysate solution (10 mg / ml, 100 μl), incubated for 2 hours to capture catalase in the solution, and placed on a magnet for 2 minutes to remove the beads. See Figure 2 C.

[0265] Evaluation of catalase expression in tissues. Fresh porcine tissues were collected for real-time PCR and western blotting. Total RNA was isolated and reverse transcribed into cDNA using standard protocols. mRNA expression was measured using the LightCycler 480 II system (Roche). Catalase mRNA expression levels were normalized to housekeeping genes (β-actin, 18S, GUS, and GAPDH) and expressed as a percentage of the negative control. For western blotting, tissue lysates were separated on SDS-PAGE gels using standard protocols. Anti-catalase (diluted 1:500 with Tris-buffered saline (TBST) buffer containing TritonX 100) and anti-β-actin (diluted 1:1000 with TBST buffer) were used as primary antibodies. Secondary antibodies (diluted 1:2000 with TBST buffer) were used for specific detection. SuperSignal TM West Femto Maximum Sensitivity Substrate generates catalase signal and uses Pierce TM ECL Western Blotting Substrate generates β-actin signal. Western Blotting at ChemiDoc TM Images were taken on an XRS+ system (Bio-Rad) and analyzed using Image Lab 3.0. Figure 2 D to 2F, 10, 11 and 12.

[0266] Microscopic analysis of polydopamine-coated tissue. Polydopamine-coated small intestine was snap-frozen and embedded in optimal cutting temperature (OCT) compound. Fixed tissue was cut into 40 μm thick sections using a cryostat microtome (Leica Biosystems). Specific peroxisome / catalase staining was performed as previously reported (M. Connock, W. Pover, Catalase particles in the epithelial cells of the guinea-pig small intestine, Histochem. J. 2, 371–380 (1970)). Uncoated tissue sections were stained with 3,3'-diaminobenzidine (DAB) substrate or tissue accelerated polymerization solution (1 mL) for 10 minutes. Slides were scanned with an Aperio digital pathology slide scanner (Leica Biosystems) and analyzed with an Aperio ImageScope (Leica Biosystems). See Figure 2 G to 2H, 5D and 26.

[0267] In vivo evaluation of tissue accelerated polymerization coating performance. All animal experiments were approved by and performed in accordance with the Animal Care Committee of the Massachusetts Institute of Technology. A large animal model, 45-55 kg Yorkshire pigs (Tufts, Medford USA) were selected to test the in vivo performance of tissue accelerated polymerization coating. In addition to a lunch snack consisting of various fruits and vegetables, pigs were fed a diet consisting of pellets (Laboratory Minipig Growth Diet 5081) every morning and evening. The pellets consisted of ground oats, alfalfa meal, semolina, soy flour, dried beet pulp, salt and other micronutrient supplements. Prior to oral administration of the tissue accelerated polymerization solution, the pigs were fed with Telazol (tiletamine / zolazepam) (5 mg kg -1 IM), xylazine (2 mg kg -1 IM) and atropine (0.05 mg kg -1 The pigs were sedated, intubated, and maintained with isoflurane (1 to 3% by inhalation) IM. In addition, gastric juice was removed from the stomach before administration of Tris-buffered tissue-accelerating polymerization solution (pH 8.5). Under endoscopic visual guidance, tissue-accelerating polymerization solution (1 ml kg -1) is administered orally via a catheter to the intestine or stomach. After delivery of the tissue-accelerating polymerization solution, gastrointestinal endoscopic imaging is used to record polydopamine formation in real time, and the endoscopic camera is placed inside and outside the tissue-accelerating polymerization solution. In order to directly evaluate polydopamine coating, a laparotomy is performed on pigs. Before applying the tissue-accelerating polymerization solution to the intestine, a non-destructive clamp is applied to the small intestine. The tissue-accelerating polymerization solution fills the intestinal cavity until the clamp site and cannot pass down to the lower small intestine. 20 minutes after application, the pigs are euthanized, and the tissue near the clamp is separated, washed and opened. All animals are euthanized before tissue harvesting. Macroscopic images of the tissue are taken to evaluate the polydopamine coating performance. During the procedure, a Cardell The pigs' blood pressure and heart rate were monitored by a multiparameter monitor (Midmark). In addition, no clinical or endoscopic evidence of gastrointestinal perforation, inflammation, or obstruction was observed during the study. Figure 3 , 4 , 14, 16, 29, 30, 31, 33 and 37.

[0268] Polydopamine probe preparation. Barium sulfate particles (20 g) were added to Tris buffer (50 mM, 1000 mL, pH 8.5), followed by the rapid addition of dopamine (10 g). The reaction mixture was kept at room temperature and stirred (600 rpm) for 3 hours. The as-synthesized polydopamine probe was purified by centrifugation (4000 rpm × 10 minutes). The purified polydopamine probe was redispersed in 100 ml of water and sonicated. The purified polydopamine probe was lyophilized for 3 days and stored at -20°C. Prior to administration, the polydopamine probe was resuspended in a tissue accelerating polymerization solution, and the polydopamine probe tissue accelerating polymerization solution was used freshly. See Figure 3 E and 15.

[0269] In vivo evaluation of polydopamine-coated intestinal retention by X-ray imaging. Pigs were sedated, intubated, and maintained with isoflurane as described above. Gastric juice was removed from the stomach prior to administration. A polydopamine probe (20 mg -1 mL -1 ) were suspended in tissue accelerating polymerization solution. The polydopamine probe was orally administered to pigs in tissue accelerating polymerization solution (3 ml kg -1) and introduced into the small intestine. An aqueous solution suspended with a conventional radio-opaque probe (unmodified barium sulfate particles) of the same concentration was administered as a control. Radiography was performed to monitor intestinal retention of the probe and polydopamine coating. For short-term stability evaluation, X-ray images were taken before and after flushing the coated area with 500 ml of water. For long-term retention evaluation, a series of X-ray images were taken at regular intervals at designated time points in the same location, during which the pigs always consumed a liquid diet. In addition, the pigs were evaluated clinically and radiographically for evidence of gastrointestinal perforation and obstruction (e.g., loss of appetite, abdominal distension, lack of feces, or vomiting). No clinical or radiographic evidence of gastrointestinal perforation and obstruction was observed during the study. See Figure 3 E to 3I, and 16.

[0270] In vivo coating of exogenous β-galactosidase on intestinal epithelium. Pigs were sedated, intubated, and maintained with isoflurane as described above. Gastric juice was removed from the stomach prior to administration. A laparotomy was performed on the pigs to open the small intestine. A chamber was placed on top of the intestinal epithelium, and then β-galactosidase (5 μg -1 mL -1 ) tissue accelerating polymerization solution (3 ml). Three control chambers with and without reagents (β-galactosidase and tissue accelerating polymerization solution) were also placed in the same pig. After 20 minutes of coating, the epithelium inside the chamber was washed 3 times with water, and the β-gal activity of the tissue was evaluated using o-nitrophenol-β-D-galactoside (ONPG) as a substrate. See Figure 4 A to 4C.

[0271] Preparation and characterization of polydopamine nanocrosslinker. Ammonium hydroxide (10 ml, 28-30% w / w) was diluted into 650 ml of ethanol-water (4:9 ratio v / v) mixed solution. The mixed solution was stirred at 30°C for 1 hour, and then 50 ml of dopamine solution (50 mg -1 mL -1 The reaction mixture was kept at 30°C for 24 hours. The as-synthesized polydopamine nano-crosslinker was purified by centrifugation (6000 rpm x 15 minutes). The purified polydopamine nano-crosslinker was redispersed in 500 ml of water and sonicated. The dry size and hydrodynamic size were measured using a transmission electron microscope (TEM, JEOL 2100F, JEOL. Ltd) and a Zetasizer Nano ZS90 instrument (Malvern Panalytical), respectively. Figure 4 D to 4E and 17A to 17B.

[0272] In vitro evaluation of blocking efficiency of tissue accelerated polymerization. Tissues were exposed to tissue accelerated polymers and washed three times with PBS buffer (1X) to remove excess polydopamine. -1 mL -1 , 12.5mg -1 mL -1 and 0mg -1 mL -1 ) of polydopamine nanocrosslinkers were suspended in tissue accelerating polymers. The coated tissues were placed in Franz cells, 100 mM nutrients (CaCl2, glutamate and glucose) were added to the chambers (sealed with parafilm), and samples were taken from the receptor compartments (with a stirring bar) for measurement after 3 hours. Fig.32 A to 32D.

[0273] In vivo evolution of an impermeable polydopamine coating for blocking glucose uptake. Pigs (fasted overnight) were sedated, cannulated, and maintained with isoflurane as described above. Gastric juice was removed from the stomach prior to administration. Polydopamine nanocrosslinkers (25 mg -1 mL -1 ) was suspended in a tissue accelerating polymerization solution. The nano cross-linker suspended tissue accelerating polymerization composition (10 ml kg -1 ) and introduced into the small intestine. The solution was applied directly to the small intestine through a catheter under visual guidance of the endoscope. For the control, 500 ml of the aqueous solution was applied in the same manner. 20 minutes after the solution was applied, a standard oral glucose tolerance test (OGTT) was performed on the pigs (Y. Lee, T. E. Deelman, K. Chen, D. S. Y. Lin, A. Tavakkoli, J. M. Karp, Therapeutic luminal coating of the intestine, Nat. Mater. 17, 834–842 (2018); E. Manell, P. Hedenqvist, A. Svensson, M. Jensen-Waern, E. Xu, Ed. Establishment of a refined oral glucose tolerance test in pigs, and assessment of insulin, glucagon and glucagon-like peptide-1 responses, PLoS One 11, e0148896 (2016)). A glucose aqueous solution (3 ml kg -1 , 500mg -1 mL -1) and introduced into the small intestine. Blood samples were collected from the central venous catheter at designated time points and immediately Glucose levels were measured using a glucose monitor (LifeScan Inc). Each data point (blood glucose change) was plotted over time, and the area under the curve was calculated for quantitative evaluation. Figure 4 A, 4D to 4E, and 33.

[0274] Praziquantel-tissue accelerated polymeric formulation. Praziquantel particles are encapsulated in polydopamine, allowing reactive groups (e.g., catechol and amine groups) on the surface of polydopamine to be chemically cross-linked and introducing praziquantel particles into the polydopamine coating. In addition, the hydrophilic polydopamine layer on the particle surface significantly improves the stability and dispersion properties of hydrophobic drug particles. Praziquantel particles (powder) (8 g) are sieved (150-300 μm mesh size) and added to Tris buffer (50 mM, 400 ml, pH 8.5), followed by rapid addition of dopamine (4 g) (J. Park, T. F. Brust, H. J. Lee, S. C. Lee, V. J. Watts, Y. Yeo, Polydopamine-based simple and versatile surface modification of polymeric nano drug carriers, ACS Nano 8, 3347–3356 (2014)). The reaction mixture is kept at room temperature and stirred (600 rpm) for 3 hours. The as-synthesized praziquantel particles were purified by centrifugation (4000 rpm x 10 min). The purified praziquantel particles were lyophilized for 3 days and stored at -20°C. Prior to administration, the praziquantel particles were resuspended in tissue accelerating polymerization solution and freshly used for tissue accelerating polymerization of praziquantel particles. See Figure 4 A, 4F and 4G.

[0275] Praziquantel concentration assessment. High performance liquid chromatography Agilent 1260 Infinity II HPLC system (Agilent Technologies, Inc.) equipped with 1260 quaternary pump, 1260 Hip ALS autosampler, 1290 thermostat, 1260 TCC control module, and 1260 diode array detector was used. OpenLab Data processing and analysis were performed using the Agilent Zorbax Eclipse XDB C software (Agilent Technologies, Inc.). For praziquantel, chromatographic isocratic separations were performed on an Agilent Zorbax Eclipse XDB C -18 4.6 × 150 mm analytical column maintained at 40 °C. The optimized mobile phase consisted of MilliQ grade water and acetonitrile with a flow rate of 1 ml min -1 , with a run time of 5 minutes. Separation was achieved using a gradient elution profile starting with 50% water and 50% acetonitrile at 0 minutes and ending with 30% water and 70% acetonitrile at 3 minutes. The injection volume was 5 μl and the selected ultraviolet (UV) detection wavelength was 217 nm. Figure 4 F and 4G.

[0276] In vivo evolution of the pharmacokinetics of praziquantel-tissue accelerated polymer. Pigs were sedated, intubated, and maintained with isoflurane as described above. Gastric juice was removed from the stomach prior to administration. Praziquantel-tissue accelerated polymer (20 mg -1 mL -1 , 1ml kg -1 ) was delivered to the small intestine. Praziquantel without tissue-accelerating polymerization was used as a control. Blood samples were collected from the ear vein at designated time points. Serum samples were separated from the blood by centrifugation (1800G×10 minutes at 4°C) and stored at -80°C for further analysis. Figure 4 F and 4G.

[0277] Serum praziquantel concentration assessment.Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS / MS) was used to analyze the praziquantel concentration in serum from in vivo experiments.The analysis was performed on a Waters ACQUITY UPLC-I-Class system combined with a Waters Xevo TQ-S mass spectrometer (Waters Corporation, Milford MA).Liquid chromatography separation was performed at 50°C on an Acquity UPLC BEH C18 (50 mm×2.1 mm, 1.7-μm particle size) column.The mobile phase consisted of 0.1% formic acid in water, 10 mM ammonium formate solution (mobile phase A) and acetonitrile: 10 mM ammonium formate, 0.1% formic acid solution (95:5 v / v) (mobile phase B).Using a certain time and solvent gradient composition, the mobile phase had a continuous flow of 0.6 ml / min. For the analysis of praziquantel, the initial composition of 80% mobile phase A was maintained for 0.50 minutes, and then the composition was linearly changed to 0% mobile phase A over the next 2.00 minutes. The composition of 0% mobile phase A and 100% mobile phase B was kept constant until 3.50 minutes. At 3.51 minutes, the composition returned to 80% mobile phase A and was maintained at this composition until the run was completed, ending at 5.00 minutes, where it was maintained for column balance. The total run time was 5.00 minutes. The mass-to-charge ratio transitions (m / z) for quantitative praziquantel were 313.22>203.09 and 313.22>83.01 (for quantitative and confirmation, respectively). As an internal standard, mebendazole, 296.06>264.03 and 296.06>76.99m / z transitions were used for quantitative and confirmation, respectively. Sample introduction and ionization were performed in positive ionization mode by electrospray ionization (ESI). Data acquisition and analysis were performed using Waters MassLynx 4.1 software. A stock solution of praziquantel was prepared at a concentration of 500 μg / ml in methanol. A twelve-point calibration curve was made in analyte-free blank serum ranging from 1.25-5000 ng / ml. 100 μl of each serum sample was spiked with 200 μl of 250 ng / ml mebendazole in acetonitrile to cause protein precipitation. The samples were vortexed, sonicated for 10 min, and centrifuged at 13,000 rpm for 10 min. 200 μl of the supernatant was pipetted into a 96-well plate containing 200 μl of water. Finally, 1.00 μl was injected onto the UPLC-ESI-MS system for analysis. See Figure 4 F and 4G.

[0278] Serum and tissue dopamine concentration assessment.Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS / MS) was used to analyze dopamine concentrations in serum and tissues from in vivo experiments. The analysis was performed on a Waters ACQUITY UPLC-I-Class system combined with a Waters Xevo TQ-S mass spectrometer (Waters Corporation, Milford MA). Liquid chromatography separation was performed at 50°C on an Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7-μm particle size) column. The mobile phase consisted of 0.1% formic acid in water, 10 mM ammonium formate solution (mobile phase A) and acetonitrile: 10 mM ammonium formate, 0.1% formic acid solution (95:5 v / v) (mobile phase B). Using a certain time and solvent gradient composition, the mobile phase had a continuous flow of 0.45 ml / min. Sample introduction and ionization were performed in positive ionization mode by electrospray ionization (ESI). Data acquisition and analysis were performed using Waters MassLynx4.1 software. A stock solution was prepared at a concentration of 500 μg / ml in methanol. A twelve-point calibration curve was prepared in blank swine serum without analytes ranging from 1.25-10000 ng / ml. 100 μl of each serum sample was spiked with 100 μl of 500 ng / ml methyldopamine (internal standard) in acetonitrile to cause protein precipitation. Then, 200 ul of 5 mg / ml fluorescein in acetonitrile was added to each sample as a derivatization reagent for both dopamine and methyldopamine to aid detection. The samples were vortexed, sonicated for 10 minutes, and centrifuged at 13,000 rpm for 10 minutes. 300 μl of the supernatant was incubated at 37°C for 60 minutes. Then 200 ul of the incubation solution was added to 200 ul of water in a 96-well plate. Finally, 10 μl was injected onto the UPLC-ESI-MS system for analysis. See Fig.31 .

[0279] The tissue samples were divided into approximately 300 mg pieces. 3% bovine serum albumin in PBS buffer was added at a volume-to-mass ratio of 2:1. The samples were homogenized at 4°C. 100 μl of each homogenate was spiked with 100 μl of 500 ng / ml methyldopamine in acetonitrile, and 200 ul of 5 mg / ml fluorescamine in acetonitrile (for derivatization). 1.00 ml of ethyl acetate was also added to the homogenized samples for extraction. The samples were vortexed, sonicated for 10 minutes, and centrifuged at 13,000 rpm for 10 minutes. After centrifugation, 300 μl of the supernatant was incubated at 37°C for 60 minutes. The samples were allowed to evaporate overnight. The evaporated samples were reconstituted with 300 μl of acetonitrile and centrifuged at 6,000 rpm for 5 minutes. 200 μl of the supernatant was transferred to a 96-well plate containing 200 μl of water. Finally, 10 μl was injected onto the UPLC-ESI-MS system for analysis. See Fig.31 .

[0280] For the analysis of dopamine fluorescamine, the initial composition of 95% mobile phase A was maintained for 0.75 minutes. Thereafter, the composition was linearly changed to 5% mobile phase A and 95% mobile phase B until 1.00 minutes. The composition was held constant at 95% mobile phase B until 3.00 minutes. At 3.25 minutes, the composition was returned to 95% mobile phase A where it was maintained to equilibrate the column for the duration of the run, ending at 4.00 minutes. The mass-to-charge transitions (m / z) used for quantification of dopamine were 414.223>137.125 and 414.223>119.115 (for quantification and confirmation, respectively). For the internal standard methyl dopamine fluorescamine, 472.223>139.139 and 472.223>278.094 m / z transitions were used for quantification and confirmation, respectively. See Fig.31 A and 31B.

[0281] Cytotoxicity assay. Vybrant MTT cell proliferation assay was used to test the cytotoxicity of polydopamine (PDA) in living cells. Polydopamine as prepared was added to cell culture medium at various concentrations (0, 10, 50, 250, 500, 1000, 1500 and 2000 μg / ml). Cytotoxicity was tested on a variety of cell lines: HeLa (ATCC), COLO320DM (ATCC), Caco-2 (ATCC), Hep3B (ATCC) and HS 895.T (ATCC), which were inoculated in 96-well plates at a density of 10,000 cells each, and kept in culture for 24 hours, and then replaced with 100 μl polydopamine solution. Cells were incubated in a cell culture incubator at 37°C for different amounts of time (6, 12, 24 hours). The cells were washed three times with PBS buffer, and then MTT solution (10 μl) and cell culture medium (100 μl) were added to each well and incubated at 37°C for 4 hours. After 4 hours, 100 μl of SDS-HCl solution was added to each well and incubated for another 4 hours (at 37°C). The absorbance at 570 nm was recorded on a 96-well plate reader (Tecan Infinite M200). See Fig.19 .

[0282] Oral toxicity test. Three groups of rats (Sprague Dawley, 150-200 g, Charles River Labs) were exposed to water (5 ml kg) for 4 weeks (4 animals per group) following the OECD published guidelines with slight modifications (OECD, Test No. 407: repeated dose 28-day oral toxicity study in rodents OECD Guide. Test. Chem. Sect. 4, OECD Publ. Paris, 1-10 (2008)). -1 ), polydopamine (15 mg mL -1 , 5ml kg -1 ) and tissue accelerated polymerization solution (5 ml kg -1 ). The solution was administered directly to the rats through a gavage needle rather than an endoscopic catheter. Body weight was measured daily for 28 days. Blood samples were collected on day 27 for hematology and blood biochemistry measurements, and food was withheld for 24 hours. On day 28, all 12 rats were euthanized and autopsies were performed. Samples of the heart, lung, liver, kidney, spleen, stomach, small intestine, and large intestine were collected for histological analysis. See Fig. 20 , 21 , 22 and 23.

[0283] Histological analysis of tissues. First, the tissues were fixed in PBS buffer (1X) containing 4% paraformaldehyde for 6 hours and then placed in PBS buffer containing 30% sucrose at 4°C overnight. The fixed tissues were embedded in paraffin and cut into 5 μm thick sections using a cryostat microtome (Leica Biosystems). The sections were stained with hematoxylin and eosin for histopathological analysis. See Figure 5 D and 23.

[0284] Polydopamine Coating of Impermeable Polycarbonate Sheets. Polycarbonate sheets were exposed to tissue accelerated polymerization solution (without H2O2) for 36 hours and washed with water to remove excess polydopamine. Fig.36 A to 36C.

[0285] Statistical analysis. All data are reported as mean ± SD, n ≥ 3 measurements per group. Two-sample t-test, one-way ANOVA and post hoc Bonferroni multiple comparison test were used to determine significance.

[0286] Overview of Selected Embodiments

[0287] The therapeutic value of the compositions, methods and kits described in the present disclosure has been evaluated in many clinical situations. By coating digestive enzymes on the small intestinal epithelium, tissue accelerated polymerization is applied to solve lactose intolerance. The results show that the β-galactosidase coated on the tissue increases the efficiency of lactose digestion by about 20 times, indicating the therapeutic utility of the present disclosure in digestive disorders and diseases. In addition, the ability of tissue accelerated polymerization technology in intestinal glucose absorption regulation is evaluated, which is urgently needed for patients with type 2 diabetes. An impermeable coating layer that acts as a glucose blocking barrier has been developed to prevent postprandial glucose intake (glucose response is reduced by about 70%). The application of tissue accelerated polymerization has been extended to improve the efficiency of drug administration under inconvenient regimens, demonstrating its ability to continuously release therapeutic agents. The disclosed method for administering praziquantel (anthelmintic) achieves persistent (over 24 hours) drug levels in the systemic circulation (half-life value increased by 10 times), with the potential to change the drug options for patients with schistosomiasis and other regimen-dependent diseases. Combined with the outstanding performance of tissue accelerated polymerization technology in human tissue specimens, these clinical applications are suitable for in vivo human testing. Tissue accelerated polymerization technology can be suitable for a wide range of technology adoption and applications in disease treatment and health management.

[0288] Example 1

[0289] Endogenous enzyme-catalyzed polydopamine growth on epithelia

[0290] To demonstrate that catalase accelerates polydopamine polymerization in a hypoxic environment, the low oxygen partial pressure in the gastrointestinal tract was simulated and the polydopamine polymerization rate was quantitatively evaluated under different reaction conditions, in which dopamine was maintained at the same concentration ( Figure 1 BD and Figure 6 A-6B). In an extremely hypoxic environment, the conventional slow polymerization of polydopamine was inhibited by 65% ​​( Figure 6 A-6B). The addition of trace amounts of hydrogen peroxide (H2O2), which acts as a strong reducing agent, prevents dopamine oxidation and nearly quenches the reaction. Figure 1 C, the slow color change of the dopamine solution from clear to light gray over two hours indicates minimal polydopamine polymerization, and the clear dopamine-H2O2 solution indicates negligible polydopamine polymerization. In contrast, the color of the dopamine solution quickly turns dark brown when both catalase and H2O2 are added, indicating that polydopamine polymerization is accelerated. In this study, using both Fourier transform infrared (FTIR) and ultraviolet-visible (UV-Vis) spectroscopy, it was confirmed that the catalase-catalyzed polymerization products from both commercial purified enzymes and crude tissue lysates were polydopamine ( Figure 7 A-7D and 8A-8C). To further quantify the effect of catalase on the polymerization rate of polydopamine, the reaction kinetics were compared by measuring the optical extinction of the solution at 700 nm, where polydopamine has an absorbance characteristic ( Figure 1 D). The signal of the catalase-polydopamine combination grew rapidly and reached a steady state within 10 minutes of the reaction. However, the extinction intensity under other conditions was relatively low even after 2 hours, wherein the same intensity level was reached within 20 seconds under catalase catalysis conditions, indicating that the polymerization rate increased by about 400 times.

[0291] Next, we evaluated whether endogenous catalase could accelerate polydopamine polymerization and coating on the small intestine to achieve tissue-accelerated polymerization on the external epithelium. The porcine gastrointestinal tract was chosen as the first model tissue due to its anatomical and physiological similarities to the human digestive system. The ex vivo tissue was incubated with a tissue-accelerated polymerization solution containing dopamine and hydrogen peroxide at concentrations within safe oral consumption levels. Figure 1 E and Fig. 9 As shown, when the mucosal side of the small intestine was exposed to a tissue-accelerating polymerization solution, a dark brown polydopamine coating was clearly observed on the epithelial surface, indicating that polydopamine was formed in situ and deposited on the anchoring points of the tissue due to the high reactivity between polydopamine and primary amines in nearby biomolecules. 14 In contrast, almost no polydopamine was found on the serosal side of the tissue after the same incubation, indicating that polydopamine polymerization is an enzyme-dependent reaction ( Figure 1E). Due to the colorimetric properties of polydopamine, these polydopamine coating processes were visualized. To further quantify the polydopamine growth rate, the amount of polydopamine coated on the small intestine was analyzed over a range of reaction times. The coating kinetics showed rapid polydopamine signal onset, reaching completion within 12 minutes ( Figure 1 F), indicating a rapid polydopamine coating process. In addition to efficiency, the specificity of tissue accelerated polymerization was also evaluated by comparing tissue accelerated polymerization coating in different parts of the gastrointestinal tract, including the esophagus, stomach, duodenum, jejunum, ileum, and colon. Figure 1 G shows that the tissue image (6 mm in diameter) reveals a prominent polydopamine coating on the duodenum and jejunum, relatively little polydopamine coating on the ileum and colon, and negligible polydopamine coating on the stomach and esophagus. This coating pattern is also confirmed by Figure 1 This exceptional efficiency and specificity of tissue-accelerated aggregation is demonstrated by quantitative polydopamine signaling analysis in H. This paves the way for downstream in vivo applications.

[0292] Example 2

[0293] Mechanisms of tissue-accelerated aggregation at the molecular, cellular and tissue levels

[0294] Before exploring the application of tissue accelerated polymerization technology, its biological mechanism was systematically studied in detail. First, it was tested whether endogenous catalase is the component that determines the catalytic polydopamine polymerization on the epithelium. The epithelial tissue of the porcine gastrointestinal tract was dissected and washed, and the outer mucus layer was removed by suction. Then, the rinsed tissue was homogenized to prepare tissue lysates, which were further diluted relative to the total protein concentration. These tissue lysates were added individually to the tissue accelerated polymerization solution, and the extinction of each solution was measured after the reaction. Figure 2 As shown in A, the signal of the polydopamine solution with small intestinal epithelial lysate is higher than that of the others, which is consistent with the tissue coating results ( Figure 1 G). In addition, similar trends were observed in the catalytic capacity analysis of these lysates by native gel electrophoresis and polydopamine staining ( Fig.10 ). Only one clear band was seen in each lane, supporting the expected role of catalase as the sole enzyme responsible for polydopamine polymerization. To further confirm the unique role of catalase, intestinal lysates were treated with a catalase-specific inhibitor to reduce catalase activity or with catalase antibody-coated magnetic beads to remove immunoprecipitated catalase. Figure 2 As shown in Figure 2B, the catalytic capacity of the lysate decreased by approximately 80% after the addition of the inhibitor and by approximately 90% when catalase was removed from the sample ( Figure 2C), indicating that the tissue accelerated polymerization process is only catalase-dependent. In addition, it was confirmed that the presence of catalase due to bacteria in the small intestinal mucus did not affect the tissue accelerated polymerization coating process ( Fig.24 A-24B and 25), showing that most of the H2O2 is not degraded or consumed in the intestinal lumen, and the amount of H2O2 is sufficient to activate oxygen release and polydopamine polymerization. In addition, it was observed that catalytic polydopamine polymerization occurs mainly in the small intestine, which is due to the higher expression of catalase in the small intestine compared with other segments of the GI tract.

[0295] It has been previously shown that human catalase is expressed at higher mRNA and protein levels in the small intestine than in other organs of the digestive tract, such as the esophagus, stomach, and large intestine. 15 , which plays a role in the coating specificity of the tissue accelerated polymerization technique. To further confirm this distinguishable catalase expression signature in the gastrointestinal epithelium, a quantitative evaluation of catalase expression along the porcine gastrointestinal tract was performed by both gene and protein analysis. Figure 2 As shown in Figure 4, high levels of catalase activity were detected in the duodenum and jejunum, while relatively low levels of catalase activity were detected in the esophagus, stomach, ileum, and colon, indicating that catalase activity is stronger in the small intestine relative to the rest of the gastrointestinal tissue. In addition, quantitative real-time polymerase chain reaction (PCR) was used to measure catalase mRNA levels in tissues. The expression level of catalase mRNA in the small intestine was approximately 10 times higher than that in other epithelial tissues ( Figure 2 E and Fig.11 A-11B), however, there was no such difference in the mRNA levels of control genes (housekeeping genes) between the small intestine and other organs ( Fig.12 A-12E). As predicted, intestinal catalase protein expression levels had a similar distribution profile compared to mRNA expression levels in the gastrointestinal tract (Western blot analysis, Figure 2 F).

[0296] Then, we worked on characterizing the interface between the polydopamine layer and the epithelium under the microscope. The chromogenic polydopamine was visualized not only by the naked eye but also by microscopy. 16 Interestingly, it was found that during the tissue acceleration polymerization process, polydopamine was first deposited on the tips of the intestinal villi and then coated the entire villus and surrounding areas ( Fig.13 Microscopic analysis revealed a thin polydopamine layer tightly packed around the outer villi ( Figure 2 G), but not in control tissue (tissue not treated to accelerate polymerization). Polydopamine was completely confined to the outer, luminal surface of the epithelium, but not inside the epithelial cells, indicating that polydopamine polymerization occurs only at the epithelial surface and that dopamine remains outside the cells throughout the reaction ( Fig.26A-26C, 27, and 28). Specific peroxisome / catalase staining studies showed that catalase is located inside peroxisomes, with high density distribution in the villi rather than in the submucosa and other inner layers ( Figure 2 H, left). Similar studies confirm that catalase “granules” exist in peroxisomes of intestinal epithelial cells. 17 To further confirm that peroxisomal catalase can catalyze polydopamine formation, dopamine was used instead of a typical peroxisomal / catalase substrate for staining. Figure 2 H (right), dark brown polydopamine spots were observed inside the epithelial cells, and the staining pattern was consistent with conventional peroxisome / catalase staining, confirming the ability of peroxisomal catalase to catalyze polydopamine polymerization in the sectioned tissue sections. No peroxisomal polydopamine pattern was observed in tissue accelerated polymerization coated samples that were subjected to tissue accelerated polymerization transluminally and then sectioned for microscopic examination without peroxisome / catalase staining ( Figure 2 G, left).

[0297] Example 3

[0298] Evaluation of tissue coating performance based on accelerated tissue polymerization in vivo

[0299] The biological mechanism of accelerated tissue aggregation has been elucidated, and the in vivo performance of this tissue coating technology has been tested in Yorkshire pigs. It is also worth mentioning that the advantages of using pigs as a large animal model include their high homology with the human genome, anatomical similarities to the human gastrointestinal tract, and physiological similarities to the human digestive system. 18,19 Under moderate sedation, the tissue-accelerating polymerization solution was orally administered to pigs under endoscopic monitoring and introduced into the small intestine via the esophagus ( Figure 3 A). After delivery of the tissue-accelerating polymerization solution, polydopamine formation was recorded in real time using a gastrointestinal endoscope, with endoscopic cameras placed inside and outside the tissue-accelerating polymerization solution ( Figure 3 B and 3C). The in vivo observations were consistent with those from ex vivo tissue encapsulation studies. Figure 3 As shown in C, a dark brown polydopamine layer was observed on the small intestinal wall 20 minutes after administration, whereas no such polydopamine coating was seen in the stomach after the same gavage ( Fig.14 A-14C). The tissue accelerated polymerization solution remains generally stable in the stomach for 30-60 minutes ( Fig.29), confirming the durability of the solution. It should be noted that all animals were fasted overnight and gastric juice was removed from the stomach before application of Tris-buffered tissue accelerating polymerization solution (pH 8.5), thus minimizing the possible effect of pH on the stability of tissue accelerating polymerization solution and polydopamine polymerization. In addition, no detectable increase in polydopamine and dopamine signals in the submucosal layer and blood was observed after tissue accelerating polymerization coating, where microscopy ( Fig.26 A-26C), UV-visible spectrum ( Fig.30 ) and liquid chromatography-tandem mass spectrometry ( Fig.31 A-31B) was used for signal measurement. In addition, no significant increase in blood pressure or heart rate was detected in any animal throughout the procedure, indicating no dopamine uptake and supporting the early safety of the tissue accelerated polymerization technique. 40 .and Figure 1 Schematic diagram of the tissue accelerated polymerization technique depicted in A Figure 1 The endoscopic video revealed that the polydopamine coating process contains three main steps. When a clear dopamine-H2O2 solution is first introduced into the small intestinal lumen, oxygen bubbles are formed and the intestinal wall quickly turns light yellow-brown, indicating the rapid diffusion of hydrogen peroxide and the initiation of polydopamine polymerization. Secondly, an increased amount of oxygen bubbles are generated at the epithelium-solution interface (camera view inside) and released into the solution (camera view outside), confirming the rapid decomposition of hydrogen peroxide and providing evidence for the oxygen release mechanism. Third, interfacial oxygen catalyzes polydopamine polymerization and adheres to the intestinal epithelium, while the tissue accelerates the polymerization solution to remain liquid and the intestinal lumen remains expanded, alleviating concerns about intestinal adhesion and obstruction. The results showed that after coating, the solution in the cavity also turned dark brown, which may be due to the diffusion of unbound polydopamine into the solution.

[0300] To directly evaluate capsule formation, laparotomy was performed on pigs. Atraumatic clamps were applied to the small intestine prior to endoscopic administration of a tissue-accelerating polymerization solution into the intestine. Figure 3 As shown in D, the tissue accelerated polymerization solution filled the intestinal cavity up to the clamp site and could not pass down to the lower small intestine. The tissue near the clamp was separated, washed and opened. Different polydopamine coating results were observed before and after the clamp site. Compared with the control section after the clamp site, the tissue immersed in the tissue accelerated polymerization solution showed an enhanced polydopamine coating density, confirming the significant tissue coating performance of the in vivo tissue accelerated polymerization.

[0301] Next, we investigated whether tissue accelerated polymerization techniques could achieve safe and prolonged intestinal retention. Polydopamine sloughed from the epithelium was visualized endoscopically after 24 hours, indicating that the coating was transient. However, given the inconvenience of endoscopic procedures, the incompatibility of frequent sedation, and the uncertainty of residual solution in the endoscopic imaging field, a more ergonomic approach to monitoring intestinal retention of polydopamine is needed. X-ray imaging is a convenient and effective tool that is commonly used for examination of the digestive tract. 19 To apply X-ray imaging to this study, a conventional X-ray contrast agent ( Fig.15 A). These polydopamine probes suspended in a tissue accelerated polymerization solution are co-coated with polydopamine on the intestinal epithelium and introduced into the polydopamine coating layer, which can be achieved by chemical cross-linking between the reactive polydopamine on the probe surface and the dopamine monomer or oligomer in the tissue accelerated polymerization solution ( Figure 3 E) 14 This co-encapsulation performance was first characterized by in vitro studies ( Fig.15 B and 15C), where the coated polydopamine probes were easily visualized by X-ray imaging, and no signal attenuation was observed after flushing the epithelial surface with water, indicating the stability of the polydopamine probe coating. In contrast, in control experiments where conventional probes or polydopamine alone were applied for coating, no obvious X-ray signals were detected. The polydopamine probes show their potential use for in vivo imaging of intestinal retention of polydopamine coatings. When a tissue-accelerated polymerization solution in which polydopamine probes were suspended was administered to healthy pigs, an X-ray signal enhancement was observed in the small intestine after the clinical procedure of a barium meal test ( Fig.16 A), revealing the shape of the intestine. However, when the same concentration of conventional probes was administered to pigs, the resulting small intestine X-ray signal was weak in comparison. It is also worth mentioning that after flushing the imaging area, the signal of the conventional probe was almost undetectable, while the polydopamine probe was still clearly visualized ( Figure 3 G), the difference in signal intensity between the two types of probes was 8.9-fold ( Figure 3 H), indicating the effective introduction of the polydopamine probe and the stable coating of polydopamine on the tissue. To monitor the intestinal retention of polydopamine over time, a series of X-ray images were taken at regular intervals at the same location ( Figure 3 G and Fig.16 B). Animals consumed a liquid diet throughout the imaging period to simulate real conditions and test the stability of the polydopamine coating in the presence of food. Quantitative signal intensity analysis was performed on the small intestine and surrounding tissues ( Figure 3I). When conventional probes were administered to pigs, X-ray signals were difficult to detect in the small intestine after flushing and exposure to food for 2-24 hours due to relatively weak tissue adhesion, resulting in rapid elimination of the probe. However, when imaging was performed with the polydopamine probe, a clear X-ray signal was observed in the small intestine after 2 hours of food exposure, which decreased by only 28% at the sixth hour, indicating prolonged retention of the polydopamine-coated intestine. The decrease in polydopamine signal may be due to the rapid regeneration of intestinal mucus by goblet cell secretion (approximately 12-24 hours) and the frequent turnover of epithelial cells by stem cell proliferation (approximately 1-5 days) 20 , where the polymer coating and the epithelium below the polydopamine fall off into the cavity. It is worth noting that after 24 hours, the intestinal X-ray signal fell back to the pre-application level, indicating complete elimination and transient retention of the polydopamine coating. The confirmation of this transient nature of the polydopamine coating indicates the safety of the tissue accelerated polymerization technology.

[0302] Example 4

[0303] Tissue-accelerated polymerization for regulated enzymatic digestion

[0304] To demonstrate the broad utility of tissue accelerated polymerization technology, the therapeutic value of this technology in regulating enzymatic digestion was evaluated ( Figure 4 A). Polydopamine is highly reactive with many chemical groups (such as amines, phenols, and thiols), making it easy to introduce functional agents into the polydopamine coating. 14 Therefore, digestive enzymes are introduced into the tissue accelerated polymerization system.

[0305] By introducing digestive enzymes into the polydopamine coating on the small intestinal epithelium, tissue accelerated polymerization technology is used to improve digestion efficiency ( Figure 4 B) According to recent studies, approximately 70% of the world's population has intestinal lactase deficiency (referring to low levels or absence of the lactase enzyme), resulting in lactose intolerance. 21,22 If exogenous β-galactosidase is coated onto the intestinal epithelium using tissue accelerated polymerization technology, it will enhance lactose digestion in the small intestine. Restoring the function of intestinal brush border enzymes (especially β-galactosidase) enables the treatment of digestive disorders and diseases, improving patient prognosis and quality of life 23,24 .

[0306] To demonstrate the ability of the tissue accelerated polymerization technique to improve lactose digestion, a tissue accelerated polymerization solution with β-galactosidase suspended therein was used to coat the small intestine of sedated pigs in which a laparotomy was performed to provide access to the small intestinal mucosa. The β-galactosidase activity of the coated epithelium was then evaluated after flushing. The coating efficiency was confirmed by analyzing the β-galactosidase activity with and without the reagents (β-galactosidase and tissue accelerated polymerization solution). Figure 4 C shows that the quantitative comparison of β-galactosidase activity indicates that after adding β-galactosidase based on tissue accelerated polymerization to the pig small intestine, the digestion efficiency increases by about 20 times. In contrast, no enhancement of β-galactosidase activity was detected in the control group (no β-galactosidase, no tissue accelerated polymerization solution, or no both), confirming that the increase in β-galactosidase activity is due to its pairing with tissue accelerated polymerization technology. In addition, when only tissue accelerated polymerization solution was applied, no decrease in digestive enzyme activity was observed compared to uncoated tissue. This consistent baseline enzyme activity indicates that neither the coating chemistry (crosslinking between polydopamine and epithelial biomolecules) nor the coated polydopamine itself inhibits the intrinsic digestive enzyme activity of the epithelium, indicating that the permeability of the polydopamine coating in the small intestine allows molecules to diffuse through. Tissue accelerated polymerization technology opens new ways to enhance digestive efficiency in the small intestine and a promising mechanism for treating digestive disorders and diseases.

[0307] Example 5

[0308] Tissue-accelerated polymerization for regulating nutrient absorption

[0309] The therapeutic value of this technology in regulating nutrient absorption was also evaluated ( Figure 4 A). Polydopamine is highly reactive with many chemical groups (such as amines, phenols, and thiols), making it easy to introduce functional agents into the polydopamine coating. 14 Therefore, nutrient blocking agents are introduced into the tissue accelerated polymerization system to create an impermeable barrier for regulating nutrient absorption.

[0310] Glucose absorption in the small intestine plays a role in the regulation of plasma glucose levels, which is often associated with metabolic disorders and systemic diseases such as obesity, hyperinsulinemia, and diabetes. 25 To prevent excess glucose intake in patients with these diseases and disorders, treatments such as gastric bypass surgery, intestinal sleeve placement, surgical adhesives, and gastrointestinal electrical stimulation have been tested. 3,7,26,27 However, these procedures are invasive and target the entire gastrointestinal tract, limiting widespread adoption. Tissue-accelerated polymerisation technology provides a non-invasive, tissue-targeted approach for modulating glucose absorption. The ability of tissue-accelerated polymerisation technology to isolate nutrient exposure, particularly glucose absorption, in the small intestine has been demonstrated.

[0311] To provide a barrier to glucose uptake, the intestinal epithelium is coated with an impermeable polydopamine coating ( Figure 4 D) Adding a nano-crosslinker to the tissue accelerated polymerization solution to produce a highly cross-linked polydopamine coating with ultra-low permeability. Fig.17 As shown in A-17B, the diameter of the additional nano-crosslinker is about 527nm, with a uniform size distribution. These hydrophilic nano-crosslinkers suspended in the tissue-accelerating polymerization solution are thereby introduced into the polydopamine coating layer, which can be achieved by chemical crosslinking between the reactive catechols and amine groups exposed on the surface of the nano-crosslinkers and dopamine monomers or oligomers in the tissue-accelerating polymerization solution. Therefore, the introduction of the crosslinker increases the number of covalent bonds inside the polydopamine coating, thereby achieving a highly dense polydopamine coating with low permeability. In order to verify the nutrient regulation function, the tissue-accelerating polymerization solution with suspended nano-crosslinkers was endoscopically applied to pigs. After the tissue-accelerating polymerization coating, oral glucose was administered to the pigs, followed by a standard oral glucose tolerance test (OGTT). Blood glucose levels are monitored to quantify intestinal glucose absorption. As Figure 4 As shown in E, control pigs without tissue accelerated polymerization coating had a significant increase in blood glucose levels after oral glucose administration. However, animals treated with tissue accelerated polymerization solution showed a reduced blood glucose response. Quantitative comparison of blood glucose levels in samples from pigs with and without tissue accelerated polymerization coating showed that glucose levels in the tissue accelerated polymerization coating were reduced by an average of 73.3% compared to the control, with six separate experiments performed and analyzed on six different pigs. This reduction in glucose response demonstrates the ability of tissue accelerated polymerization technology to effectively prevent postprandial glucose intake. In addition, the tissue accelerated polymerization barrier showed effective blocking capabilities for different nutrients, and the blocking efficiency was adjusted by adjusting the cross-linking density of the tissue accelerated polymerization coating layer ( Fig.32 A-32D). In addition, it was confirmed that the glucose absorption barrier was transient and normal glucose absorption was restored after 24 hours ( Fig.33 These results address the unmet clinical need for non-invasive blockade of glucose absorption in the small intestine and demonstrate the feasibility of tissue accelerated polymerization as a treatment approach for patients with type 2 diabetes.

[0312] Example 6

[0313] Tissue-accelerated polymerization for controlled drug release

[0314] The therapeutic value of this technology in drug release regulation was also evaluated ( Figure 4 A). Polydopamine is highly reactive with many chemical groups (such as amines, phenols, and thiols), making it easy to introduce functional agents into the polydopamine coating. 14Therefore, anthelmintics were introduced into the tissue accelerated polymerization system to evaluate the system as used for oral drug delivery, demonstrating its ability to release the therapeutic agent continuously in the small intestine.

[0315] The development of oral sustained-release drugs is limited by the rapid transit time of therapeutic agents in the gastrointestinal tract. Attempts to prolong the gastrointestinal retention of drugs, especially in the small intestine (i.e., an environment more compatible with sensitive drugs than the harsh acidity of the stomach), have been made with limited success. 19,28 Praziquantel was chosen as a model drug to test the ability of the tissue-accelerated polymerization technique to prolong intestinal retention. Praziquantel is the only anthelmintic commonly used to treat schistosomiasis, a major neglected tropical disease caused by intestinal parasitic worms that affects more than 200 million people worldwide. 29,30 Praziquantel, which has a half-life of 1 to 1.5 hours in humans, is recommended to be taken orally three times daily, 5 hours apart, a regimen that is difficult to adhere to. Alternative technologies that can prolong intestinal retention to reduce dosing frequency are urgently needed.

[0316] like Figure 4 As shown in F, praziquantel particles (powder) are coated on the small intestinal epithelium using tissue accelerated polymerization technology, enabling prolonged intestinal retention and sustained release. Praziquantel particles (powder) are encapsulated in polydopamine to introduce the drug into the polydopamine coating. Pharmacokinetic studies were conducted on praziquantel-tissue accelerated polymerization solutions administered orally in pigs to study the release kinetics of praziquantel-tissue accelerated polymerization solutions. After administration, blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 24 and 48 hours, and their serum praziquantel concentrations were further analyzed by liquid chromatography-tandem mass spectrometry. As Figure 4 G, quantitative comparison of pharmacokinetics revealed that the retention time of praziquantel with tissue accelerated polymerization solution was prolonged relative to conventional administration. When the praziquantel control (without tissue accelerated polymerization solution) was conventionally administered, the drug was rapidly cleared from the blood with an elimination period of 2-6 hours, and the drug was undetectable at or after 24 hours. However, blood levels of praziquantel administered by tissue accelerated polymerization technology persisted for more than 6 hours, with 20.0 ng mL still detectable at 24 hours. -1 The average concentration was even higher than the average control drug concentration at 6 hours (15.1 ng mL -1 ). A non-compartmental pharmacokinetic model was used to quantitatively analyze pharmacokinetic parameters (including area under the curve (AUC) and half-life). The results of three large animal studies showed that praziquantel (905.8 ng h mL -1 , with tissue accelerated polymerization solution) and praziquantel control (222.4 ng h mL -1) between the AUC values ​​of 1.5 and 2.5 hours. In addition, when administered using the tissue accelerated polymerization technique, the half-life of praziquantel increased 10-fold (from 1.3 hours to 13 hours), indicating prolonged intestinal retention of the drug. It is noteworthy that praziquantel is primarily metabolized by cytochrome P450 enzymes, especially CYP3A4, which is present in the small intestine and liver. 30,38 To confirm that accelerated polymer coating of the tissue did not affect drug metabolism, CYP3A4 activity was measured and compared in epithelia with and without polydopamine coating ( Fig.34 ), and no changes in CYP3A4 activity were observed after tissue accelerated polymerization coating. The sustained release of praziquantel by tissue accelerated polymerization technology expands the effectiveness of treatment options for schistosomiasis and is also suitable for diseases where regimen compliance is important for efficacy.

[0317] Example 7

[0318] Ultrafast and Stable Encapsulation of Human Tissue Using Tissue Accelerator Polymerization

[0319] Tissue accelerated polymerization technology is applicable to human tissue and is suitable for clinical translation. Freshly resected tissue specimens from human small intestine were coated to test compatibility with tissue accelerated polymerization technology. Similar to the results of porcine tissue coating ( Figure 1 E) Polydopamine coating was clearly observed on the surface of human small intestine ( Figure 5 A). However, polydopamine signaling was generated more rapidly in human tissue compared to porcine tissue, where coating completion time was reduced from 12 minutes to 3 minutes ( Figure 5 B), which may be due to the higher level of catalase in the human small intestine. The relationship between intestinal catalase activity and tissue accelerated polymerization coating density was analyzed using human, porcine and mouse tissue specimens, and a significant correlation between tissue accelerated polymerization coating density and enzyme activity level was obtained ( Fig.18 A-18B). Human and porcine small intestines exhibited 60% more polydopamine production compared to rat small intestine, due to their strong enzymatic activity. Similar tissue accelerated polymerization efficiencies (between humans and pigs) may be due to their genomic and proteomic similarities. To further demonstrate the robustness of the tissue accelerated polymerization technology for human tissue coating, tissue specimens from 3 donors with polydopamine coating were tested. In addition, five evaluations were performed on random sites of the small intestine (from donors of different ages, races, and genders) to confirm consistent polydopamine coating performance. In addition, it was confirmed that the human and porcine GI tracts exhibited similar tissue accelerated polymerization patterns ( Fig.35 A-35B), due to higher expression of catalase in the small intestine of both species compared with other segments of the GI tract 15 .like Figure 5C shows that 30 tissue images (6 mm in diameter) revealed highly consistent polydopamine coating and signal enhancement. These tissue specimens coated by tissue accelerated polymerization technology were further examined by microscopy. Consistent with the pig results ( Figure 2 G), Microscopic and histological analysis of frozen and formalin-fixed paraffin-embedded (FFPE) specimens showing a thin polydopamine coating on the outer villi of the human small intestine ( Figure 5 D) After exposure to the tissue accelerated polymerization solution, the epithelial layer remained intact (with staining patterns similar to unexposed controls), indicating the absence of tissue toxicity.

[0320] To further evaluate the biocompatibility of the tissue accelerated polymerization technique, the cytotoxicity of polydopamine on various cell lines was characterized: HeLa, COLO320DM, Caco-2, Hep3B and HS 895.T ( Fig.19 ), it was concluded that no significant cytotoxicity was observed after 6-48 hours of in vitro incubation. In addition, the oral toxicity of the tissue accelerated polymerization solution was systematically evaluated by following the slightly modified guidelines published by the OECD. Therefore, based on the repeated dose 28-day toxicity study method recommended by Good Laboratory Practice (GLP), rats were exposed to the tissue accelerated polymerization solution over a period of 4 weeks. During the 28-day exposure period, no significant differences in body weight were observed between rats exposed to the tissue accelerated polymerization solution and the control ( Fig. 20 A-20C). Additional hematology measurements, blood biochemistry tests ( Fig.21 and 22 ) and histopathological examination further confirmed the absence of oral toxicity ( Fig.23 ), supporting the favorable biocompatibility of tissue accelerated polymerization technology, indicating minimized risks for upcoming preclinical and clinical trials.

[0321] The stability of human tissue coating is a factor in the clinical translation of tissue accelerated polymerization technology. The small intestine provides a dynamic environment in which physical forces (peristalsis and segmental motility) and chemical exposure (chyme, gastric acid, and intestinal fluid) have the potential to damage the polydopamine coating ( Fig.36 A-36C). The stability of the tissue coating was evaluated under a range of physical and chemical conditions. Figure 5 As shown in E, no decrease in polydopamine signal was observed under mechanical agitation and scraping. Quantitative signal intensity analysis showed that approximately 80% of polydopamine remained strongly attached even after vigorous scraping of the small intestine with the scalpel spine ( Figure 5 F). In addition, the stability of the polydopamine coating was further confirmed by incubating the polydopamine coated human tissue in different solutions for 24 hours. Figure 5G showed that the polydopamine coating was highly stable in simulated intestinal and gastric fluids and other extreme conditions (ethanol and concentrated saline). These results confirm the coating stability of the tissue accelerated polymerization technology in the human small intestine and indicate the feasibility of broad applicability.

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Claims

1. Use of a composition comprising a monomer and an oxygen source in the preparation of a medicament for forming a polymer in situ in a subject, wherein the oxygen source contacts a catalyst endogenous to the subject and releases oxygen from the oxygen source to polymerize the monomer, wherein the monomer is dopamine or a salt thereof, the oxygen source is hydrogen peroxide or urea hydrogen peroxide, and the endogenous catalyst is selected from catalase or peroxidase, wherein the peroxidase is eosinophil peroxidase, lactoperoxidase, or myeloperoxidase.

2. The use according to claim 1, wherein the endogenous catalyst is catalase.

3. The use according to claim 1, wherein the catalase is a bacterial catalase.

4. The use of claim 1, wherein the endogenous catalyst is located in the gastrointestinal (GI) tract of the subject.

5. The use of claim 1, wherein the endogenous catalyst is located in the upper GI tract of the subject.

6. The use according to claim 1, wherein the endogenous catalyst is located in the stomach of the subject.

7. The use according to claim 1, wherein the composition further comprises an enzyme, a nutrient blocker, a nutrient formulation, a radioprotectant, an active pharmaceutical ingredient, a diagnostic agent, or a combination thereof.

8. The use according to claim 1, wherein the composition is administered orally.

9. The use of claim 1, wherein at least one of the monomer and the oxygen source is stable in the stomach of the subject.

10. The use of claim 1, wherein at least one of the monomer and the oxygen source is stable in the stomach of the subject for at least 30 minutes.

11. The use of claim 1, wherein at least one of the monomer and the oxygen source is stable in the stomach of the subject for at least 60 minutes.

12. The use of claim 1, wherein at least one of the monomer and the oxygen source is stable in that it does not decompose in the stomach of the subject.

13. The use according to claim 1, wherein the composition comprises 0.001 to 1000 mg / mL of dopamine.

14. The use according to claim 1, wherein the composition comprises 0.01 to 100 mg / mL of dopamine.

15. The use according to claim 1, wherein the composition comprises 0.01 to 50 mg / mL of dopamine.

16. The use according to claim 1, wherein the composition comprises 1 to 20 mg / mL of dopamine.

17. The use according to claim 1, wherein the composition comprises 10 mg / mL of dopamine.

18. The use according to claim 1, wherein the composition comprises 0.01 to 100 mM of the oxygen source.

19. The use according to claim 1, wherein the composition comprises 0.1 to 50 mM of the oxygen source.

20. The use according to claim 1, wherein the composition comprises 1 to 30 mM of the oxygen source.

21. The use according to claim 1, wherein the composition comprises 20 mM of the oxygen source.

22. The use according to claim 1, wherein the composition has a pH of 7 to 10.

23. The use according to claim 1, wherein the composition has a pH of 7 to 9.

24. The use according to claim 1, wherein the composition has a pH of 8.

5.

25. The use according to claim 1, wherein the composition has a pH of 7.

4.

26. The use according to claim 1, wherein the composition is in liquid or solid dosage form.

27. The use according to claim 1, wherein the composition is in the form of a solution, a gel, a tablet, or a capsule.

28. The use of claim 1, wherein the polymer is formed upon contact with the epithelium of the subject.

29. The use of claim 1, wherein the polymer adheres to the tissue of the subject.

30. The use according to claim 29, wherein the tissue is epithelium.

31. Use according to claim 30, wherein the epithelium is intestinal epithelium.

32. The use of claim 1, wherein the polymer is bound to an amine moiety exposed on the luminal surface of the epithelium of the subject.

33. The use according to claim 1, wherein the polymer is formed in less than 20 minutes.

34. The use of claim 1, wherein the polymer does not form on the epithelium of the gastrointestinal tract outside the small intestine of the subject.

35. The use of claim 1, wherein the polymer is formed on the epithelium of one or more of the duodenum, jejunum, ileum, colon, esophagus, or stomach of the subject.

36. The use of claim 1, wherein the polymer is formed on the epithelium of the duodenum of the subject.

37. The use of claim 1, wherein the polymer does not form on the epithelium of one or more of the esophagus or stomach of the subject.

38. The use of claim 1, wherein less polymer is formed in the ileum and colon of the subject compared to the duodenum and jejunum of the subject.

39. The use of claim 1, wherein the polymer does not form on the stomach and esophagus of the subject.

40. The use according to claim 1, wherein the polymer forms a temporary barrier in vivo.

41. The use according to claim 1, wherein after 6 hours, 20% to 70% of the transient barrier remains.

42. The use of claim 1, wherein the polymer is cleared from the subject after 24 hours.

43. The use of claim 1, wherein the polymer and composition further comprises an enzyme.

44. The use according to claim 43, wherein the enzyme is a digestive enzyme.

45. The use according to claim 44, wherein the digestive enzyme is lactase, peptidase, sucrase, maltase, amylase, lipase, or protease.

46. ​​The use according to claim 1, wherein the medicament is used to improve the digestive efficiency of the subject.

47. The use according to claim 1, wherein the medicament is for enhancing the digestion of lactose by the subject.

48. The use according to claim 1, wherein the medicament is for treating lactose intolerance in the subject.

49. The use according to claim 44, wherein the digestive enzyme is β-galactosidase.

50. The use according to claim 49, wherein the β-galactosidase increases the digestion efficiency of lactose in the subject by 20 times.

51. The use of claim 40 or 41, wherein the polymer barrier does not inhibit the intrinsic digestive enzyme activity of the epithelium of the subject.

52. The use of claim 1, wherein the polymer and composition further comprises a nutrient blocking agent.

53. The use according to claim 1, wherein the medicament is used to prevent nutrient absorption in the subject.

54. The use according to claim 1, wherein the medicament is used to regulate or modulate glucose absorption in the subject.

55. The use according to claim 1, wherein the medicament is used to regulate or modulate sugar absorption in the subject.

56. Use according to claim 55, wherein the sugar is selected from the group consisting of glucose, lactose, fructose, maltose, dextrose, galactose, sucrose and isomaltose.

57. The use of claim 1, wherein the drug prevents absorption for less than 24 hours.

58. The use of claim 1, wherein the drug blocks absorption for less than 6 hours.

59. The use according to claim 1, wherein the medicament is for treating obesity in the subject.

60. The use according to claim 1, wherein the medicament is for treating hyperinsulinemia in the subject.

61. The use according to claim 1, wherein the medicament is for treating diabetes in the subject.

62. The use according to claim 61, wherein the diabetes is type 2 diabetes.

63. The use according to claim 1, wherein the composition further comprises a cross-linking agent.

64. The use according to claim 63, wherein the cross-linking agent comprises nanoparticles.

65. The use according to claim 63, wherein the cross-linking agent comprises polydopamine.

66. The use according to claim 63, wherein the cross-linking agent is a nutrient blocking agent.

67. The use according to claim 63, wherein the cross-linking agent increases the nutrient blocking ability of the polymer.

68. The use according to claim 54 or 56, wherein the absorption is regulated by adjusting the cross-linking density of the polymer.

69. The use according to claim 55, wherein the absorption is regulated by adjusting the cross-linking density of the polymer.

70. The use of claim 54 or 56, wherein the medicament reduces glucose absorption in the subject by at least 50%, at least 60%, or at least 70% within a period of 3 hours after administration of the medicament.

71. The use of claim 54 or 56, wherein the medicament reduces glucose absorption in the subject by at least 50%, at least 60%, or at least 70% within a period of 2 hours after administration of the medicament.

72. The use of claim 54 or 56, wherein the medicament reduces glucose absorption in the subject by at least 50%, at least 60%, or at least 70% within a period of 1 hour after administration of the medicament.

73. The use of claim 68, wherein the medicament reduces glucose absorption in the subject by at least 50%, at least 60%, or at least 70% within a period of 3 hours after administration of the medicament.

74. The use of claim 68, wherein the medicament reduces glucose absorption in the subject by at least 50%, at least 60%, or at least 70% within a 2 hour period following administration of the medicament.

75. The use of claim 68, wherein the medicament reduces glucose absorption in the subject by at least 50%, at least 60%, or at least 70% within a period of 1 hour after administration of the medicament.

76. The use according to claim 1, wherein the composition further comprises an active pharmaceutical ingredient.

77. The use according to claim 76, wherein the active pharmaceutical ingredient is retained or encapsulated in the polymer.

78. The use of claim 76, wherein the drug is one that prolongs the residence time of an active pharmaceutical ingredient at a polymerized site in the subject compared to administration of the active pharmaceutical ingredient in the absence of the polymer.

79. The use of claim 76, wherein the drug is a drug that provides sustained release of an active pharmaceutical ingredient compared to administration of the active pharmaceutical ingredient in the absence of the polymer.

80. The use of claim 76, wherein the drug is one that provides for less frequent dosing of an active pharmaceutical ingredient compared to administering the active pharmaceutical ingredient in the absence of the polymer.

81. The use of claim 76, wherein the drug is one that increases the half-life of the active pharmaceutical ingredient compared to administration of the active pharmaceutical ingredient in the absence of the polymer.

82. The use of claim 76, wherein the drug is one that increases the AUC of the active pharmaceutical ingredient compared to when the active pharmaceutical ingredient is administered in the absence of the polymer.

83. The use of claim 76, wherein the drug is a drug that modulates the C of the active pharmaceutical ingredient compared to administration of the active pharmaceutical ingredient in the absence of the polymer. max of medicines.

84. The use of claim 76, wherein the drug is a drug that modulates the T of the active pharmaceutical ingredient compared to when the active pharmaceutical ingredient is administered in the absence of the polymer. max of medicines.

85. The use of claim 77, wherein the drug is one that prolongs the residence time of an active pharmaceutical ingredient at a polymerized site in the subject compared to administration of the active pharmaceutical ingredient in the absence of the polymer.

86. The use of claim 77, wherein the drug is a drug that provides sustained release of an active pharmaceutical ingredient compared to administration of the active pharmaceutical ingredient in the absence of the polymer.

87. The use of claim 77, wherein the drug is one that provides for reduced frequency of dosing of an active pharmaceutical ingredient compared to administration of the active pharmaceutical ingredient in the absence of the polymer.

88. The use of claim 77, wherein the drug is one that increases the half-life of the active pharmaceutical ingredient compared to administration of the active pharmaceutical ingredient in the absence of the polymer.

89. The use of claim 77, wherein the drug is one that increases the AUC of the active pharmaceutical ingredient compared to administration of the active pharmaceutical ingredient in the absence of the polymer.

90. The use of claim 77, wherein the drug is a drug that modulates the C of the active pharmaceutical ingredient compared to administration of the active pharmaceutical ingredient in the absence of the polymer. max of medicines.

91. The use of claim 77, wherein the drug is a drug that modulates the T of the active pharmaceutical ingredient compared to when the active pharmaceutical ingredient is administered in the absence of the polymer. max of medicines.

92. The use according to claim 83, wherein the modulation is an increase.

93. The use according to claim 83, wherein the modulation is a decrease.

94. The use according to claim 84, wherein the modulation is an increase.

95. The use according to claim 84, wherein the modulation is a decrease.

96. The use according to claim 90, wherein the modulation is an increase.

97. The use according to claim 90, wherein the modulation is a decrease.

98. The use according to claim 91, wherein the modulation is an increase.

99. The use according to claim 91, wherein the modulation is a decrease.

100. The use according to claim 1, wherein the drug does not affect the metabolism of the drug.

101. The use according to any one of claims 76-99, wherein the active pharmaceutical ingredient is an antiparasitic drug.

102. The use according to any one of claims 76-99, wherein the active pharmaceutical ingredient is an anthelmintic.

103. The use according to any one of claims 76-99, wherein the active pharmaceutical ingredient is praziquantel.

104. The use according to any one of claims 76-99, wherein the medicament is for treating schistosomiasis in the subject.

105. The use according to claim 1, wherein the composition further comprises a radioprotectant.

106. The use according to claim 1, wherein the medicament is used to target the small intestine.

107. The use according to claim 1, wherein the medicament is used to reduce small intestinal uptake.

108. The use according to claim 1, wherein the medicament is used to reduce the uptake of one or more nutrients and active pharmaceutical ingredients by the small intestine.

109. The use according to claim 1, wherein the medicament is used to increase the residence time in the small intestine.

110. The use according to claim 1, wherein the medicament is used to increase the residence time of one or more nutrients and / or active pharmaceutical ingredients in the small intestine.

111. The use according to claim 1, wherein the drug keeps the intestinal lumen dilated.

112. The use according to claim 1, wherein the medicament is for treating or preventing intestinal adhesions in the subject.

113. The use according to claim 1, wherein the medicament is for treating or preventing intestinal obstruction in the subject.

114. The use according to claim 1, wherein the medicament is for treating small intestinal bleeding in the subject.

115. The use according to claim 1, wherein the polymer modulates absorption in the small intestine.

116. The use of claim 1, wherein the polymer regulates digestion in the small intestine.

117. The use of claim 1, wherein the polymer modulates absorption of one or more nutrients or active pharmaceutical ingredients or a combination thereof in the small intestine.

118. The use of claim 1, wherein the polymer retards absorption of one or more nutrients or active pharmaceutical ingredients, or a combination thereof, into the epithelium on which the polymer is formed.

119. The use of claim 1, wherein the polymer hinders absorption of one or more nutrients or active pharmaceutical ingredients, or a combination thereof, into the bloodstream of the subject.

120. The use according to claim 1, wherein the medicament is for immobilizing an enzyme in the subject.

121. The use according to claim 1, wherein the medicament is for delivering an active pharmaceutical ingredient to the subject.

122. The use according to claim 1, wherein the medicament is for supplementing digestion in a subject.

123. The use according to claim 1, wherein the polymer is non-toxic.

124. The use according to claim 1, wherein the polymer is stable to physical and chemical forces.

125. The use according to claim 1, wherein the polymer is stable to one or more of intestinal fluid, gastric acid, chyme, ethanol and saline.

126. The use of claim 1, wherein the polymer decomposes less than 10% when exposed to one or more of intestinal fluid, gastric acid, chyme, ethanol, or saline.

127. The use according to claim 124, wherein the physical force is selected from one or more of peristalsis and segmental movement.

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