Nanometer delivery system and preparation method and application thereof
By using a core-shell structured nanodelivery system composed of dendritic mesoporous silica nanoparticles and Bletilla striata polysaccharide, the problem of single-function wound repair materials has been solved, achieving synergistic effects of rapid hemostasis, antibacterial properties, and tissue repair, while improving drug loading capacity and stability.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-01-07
- Publication Date
- 2026-04-03
AI Technical Summary
Existing wound repair materials cannot fulfill multiple functions, have poor drug loading and repair effects, traditional dressings have a single function, modern functional dressings have limited drug loading capacity, and nanomedicine delivery systems have low drug loading and poor stability.
A core-shell nanodelivery system using dendritic mesoporous silica nanoparticles as the core and Bletilla striata polysaccharide as the outer shell is constructed through a two-step method to build dendritic channels and amino modification to provide reaction sites, thereby achieving stable encapsulation of Bletilla striata polysaccharide and forming a time-sequence control of hemostasis followed by treatment.
It achieves a synergistic effect of rapid hemostasis, antibacterial properties and tissue repair, improves drug loading and stability, and significantly enhances wound repair.
Smart Images
Figure CN121775159A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of drug delivery and wound repair applications using nanoporous materials, and particularly to a nanodelivery system, its preparation method, and its applications. Background Technology
[0002] Wound healing is crucial and urgently needs to be addressed in clinical medicine. Repairing complex wounds such as acute traumatic bleeding, chronic infected wounds (e.g., diabetic foot ulcers, pressure ulcers), and large-area burns presents significant challenges. These wounds heal slowly and are prone to serious complications such as sepsis, threatening patients' lives and reducing their quality of life. Therefore, finding effective wound repair methods is of paramount importance.
[0003] An ideal wound dressing needs to have several key functions: rapid hemostasis to buy time for subsequent treatment; long-lasting antibacterial effect to reduce the risk of infection; regulation of inflammation to maintain a balanced response; and promotion of cell proliferation and angiogenesis to accelerate healing and improve quality.
[0004] Currently, wound repair materials are diverse, but each has its shortcomings. Traditional dressings (such as gauze and cotton pads) have a single function, passively covering the wound and lacking active repair capabilities. Changing them can easily damage newly formed tissue, leading to delayed healing and new problems. Modern functional dressings (such as hydrogels, sponges, and films) offer advantages in moisture retention and breathability, but their drug-carrying capacity is limited, and drug release occurs in a burst mode, resulting in unstable therapeutic effects. Nanoparticle drug delivery systems (such as liposomes and polymer micelles) can improve drug bioavailability, but they generally suffer from low drug loading, poor stability, and a lack of tissue adhesion and tissue regeneration promotion capabilities.
[0005] In recent years, mesoporous silica nanoparticles have attracted attention in the field of drug delivery due to their unique physicochemical properties, with significant advantages such as high specific surface area, large pore volume, ease of surface modification, and good biocompatibility. Among them, dendritic large-pore mesoporous silica nanoparticles (DMSNs) stand out due to their unique pore structure. DMSNs have a three-dimensional dendritic framework and a large central radial emission mesopore structure. Compared with the two-dimensional channels of ordinary MSNs, DMSNs have larger pore diameters (34-45 nm), larger specific surface areas, and higher loading capacities, showing broad application prospects.
[0006] Combining natural polysaccharides (such as hyaluronic acid, chitosan, and alginate) with inorganic carriers is a common strategy for endowing materials with bioactivity. Bletilla striata polysaccharide, as an active ingredient of the traditional Chinese medicine Bletilla striata, has been shown in studies to possess excellent hemostatic, antibacterial, anti-inflammatory, and fibroblast proliferation and angiogenesis-promoting effects, making it a highly promising wound repair material.
[0007] Currently, there are no reports on the application of drug-loaded nanoparticles made by coating Bletilla striata polysaccharides onto dendritic mesoporous silica nanoparticles for wound repair. Summary of the Invention
[0008] In view of this, the present invention proposes a nanodelivery system, its preparation method and application, to solve the problem that existing wound repair materials cannot take on multiple functions and have poor drug loading and repair effects.
[0009] The specific technical solution of this invention is as follows: A method for preparing a nanodelivery system, comprising: Dendritic mesoporous silica nanoparticles were prepared as the core carrier; amino functional groups were modified on the dendritic mesoporous silica nanoparticles to provide reaction sites; the carboxyl groups of Bletilla striata polysaccharide were activated to enable the polysaccharide to have bonding ability; the amino-modified dendritic mesoporous silica nanoparticles were mixed and reacted with the activated Bletilla striata polysaccharide to form a core-shell structured nanodelivery system with dendritic mesoporous silica as the core and Bletilla striata polysaccharide as the shell, so as to realize the time-sequence control function of hemostasis before treatment.
[0010] Specifically, when preparing dendritic mesoporous silica nanoparticles, a surfactant template-directed method is used, in which organic solvents are added to regulate the pore morphology and form a dendritic pore structure to increase the specific surface area and pore volume.
[0011] Specifically, the amino functional group modification is carried out by heating and refluxing in an organic solvent using a silane coupling agent, so that the amino groups are stably bound to the surface of dendritic mesoporous silica.
[0012] Specifically, the carboxyl groups of Bletilla striata polysaccharide are activated using carbodiimide and hydroxysuccinimide as activators, and the mixture is stirred under light-protected conditions to promote carboxyl activation.
[0013] Specifically, the mixing reaction is carried out in a dark environment at room temperature. Stirring induces the formation of amide bonds between amino and carboxyl groups, thereby achieving a firm coating of Bletilla striata polysaccharide shell.
[0014] Specifically, the preparation of dendritic mesoporous silica nanoparticles includes the step of removing the template agent and eliminating surfactant residues by high-temperature calcination.
[0015] Specifically, after the reaction is complete, unreacted components are removed through separation and washing to obtain a pure core-shell structured nanodelivery system.
[0016] Specifically, the synthesis of dendritic mesoporous silica nanoparticles employs a two-step method to construct pores. The first step forms a basic mesoporous framework, and the second step expands the pores using organic solvents to form a dendritic structure.
[0017] A nanodelivery system is prepared using the above-described method. The nanodelivery system comprises a dendritic mesoporous silica core loaded with a therapeutic drug and a Bletilla striata polysaccharide shell, forming a core-shell structure. The shell is used for immediate hemostasis, and the core is used for sustained drug release therapy.
[0018] An application of a nanodelivery system is characterized in that the nanodelivery system is applied to the field of wound repair to achieve hemostasis, antibacterial and tissue repair functions.
[0019] The beneficial effects of this invention are as follows: (1) Through the core-shell structure design, the outer shell of Bletilla striata polysaccharide can quickly stop bleeding and reduce inflammation after contacting the wound, while the core drug is released slowly as the outer shell degrades, forming a synergistic effect of stopping bleeding first and then treating, and simultaneously improving the anti-infection and tissue repair effects. (2) A two-step method was used to synthesize dendritic pore structures and organic solvents were used to regulate the formation of ultra-large specific surface area and pore volume, which significantly improved the drug loading capacity and effectively improved the problem of insufficient drug loading capacity of traditional mesoporous silica. (3) By modifying the surface of dendritic macroporous silica with amino groups, stable binding sites are provided for Bletilla striata polysaccharides, thus achieving a firm coating of the shell; (4) The nanodelivery system triggers a rapid hemostatic response in the wound environment, significantly improving hemostatic efficiency; (5) The core drug released after the outer shell degrades continuously inhibits the proliferation of pathogenic microorganisms and enhances the wound's anti-infection ability. Attached Figure Description
[0020] To more clearly illustrate the technical solutions in the embodiments of this application, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0021] Figure 1 This is an SEM (Scanning Electron Microscope) image of the DMSN of this invention; Figure 2 This is a TEM (Transmission Electron Microscope) image of the DMSN of this invention; Figure 3 The infrared spectra of DMSN, DMSN-NH2, and DMSN-BSP of the present invention are shown, where A is the infrared spectrum of DMSN, B is the infrared spectrum of DMSN-NH2, and C is the infrared spectrum of DMSN-BSP. Figure 4This is a comparison chart of the BCI (Blood Clotting Index) test results of DMSN and DMSN-BSP of the present invention; Figure 5 The colony plate coating results of this invention directly reflect the antibacterial effect of DMSN-BSP against Escherichia coli and Staphylococcus aureus through colony counting. Detailed Implementation
[0022] To make the technical problems to be solved, the technical solutions, and the beneficial effects of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.
[0023] This invention proposes a nanodelivery system, its preparation method, and its application. The nanodelivery system comprises a core of dendritic mesoporous silica loaded with therapeutic drugs and a shell of Bletilla striata polysaccharide, wherein the therapeutic drug is selected from at least one of antibiotics or growth factors. The core function of this nanodelivery system is that upon contact with the wound, the Bletilla striata polysaccharide shell immediately exerts hemostatic and anti-inflammatory effects. Subsequently, the shell degrades in the wound environment to release the drug loaded within the core, achieving a synergistic effect of anti-infection and tissue repair, thus completing a sequential relay process of first stopping bleeding and protecting the wound, followed by enhanced treatment.
[0024] The synthesis of dendritic macroporous silica (DLMSNs) is a key step in the preparation of nanodelivery systems. It utilizes a two-step method to construct dendritic channel structures to enhance specific surface area and pore volume. The specific steps are as follows: First, weigh 12.5 g of hexadecyltrimethylammonium bromide (CTAB) and place it in a container. Add 37.5 mL of H₂O and heat the mixture in an ultrasonic device at 60 °C for 0.5 h until completely dissolved, thus preparing 50 mL of a 25% (mass fraction) CTAB solution for later use. Next, transfer 24 mL of the prepared solution to a 100 mL round-bottom flask and add 180 μg of triethylamine (T... EA) and 36 mL of H2O were added, and the mixture was stirred continuously at 60 °C and 200 rpm for 1 h using a magnetic stirrer to ensure homogeneous mixing. Then, 16 mL of cyclohexane and 4 mL of tetraethyl orthosilicate (TEOS) were slowly added dropwise along the wall of the round-bottom flask, and stirring was continued at 60 °C and 100 rpm for 12 h. This process promoted the hydrolysis and condensation of the silicon source to form mesoporous silicon nanoparticles (MSNs) samples. The resulting samples were then centrifuged at 1100 rpm for 5 min in a high-speed centrifuge. The precipitate was collected and washed repeatedly with ethanol at least three times to remove unreacted reagents. The samples were then allowed to stand in a ventilated environment. The residual organic solvent was allowed to evaporate naturally in a windy environment. The sample was then transferred to a vacuum drying oven and dried at 60°C for 4 hours. Finally, the residual temperature (approximately 60°C) was used to maintain the sample for 12 hours to ensure complete drying. Next, 70 μg of triethylamine (TEA) and 12 mL of distilled water were added to the dried sample. The sample was then treated with an ultrasonic device to ensure complete dissolution. 8 mL of the previously prepared 25% (mass fraction) hexadecyltrimethylammonium bromide (CTAB) solution was added, and the sample was magnetically stirred at 60°C for 1 hour. Subsequently, 17.5 mL of chlorobenzene and 1.64 mL of tetraethyl orthosilicate (TEOS) were added, and the sample was stirred at room temperature for 12 hours to induce dendritic channel formation. After the reaction was complete, the sample solution was centrifuged at 1100 rpm for 10 min. The separated precipitate was the dendritic macroporous silica (DLMSNs) sample. It was placed in a ventilated area to allow the organic solvent to evaporate, and then placed in a vacuum drying oven at 60°C for 4 h. Finally, the weight of the dried sample was weighed and transferred to a muffle furnace for calcination. The calcination program was set to reach 550°C at a heating rate of 10°C per minute and maintain it for 5 h (the heating phase took 55 min and the isothermal phase lasted 4.08 h). This high-temperature process effectively removed the template agent cetyltrimethylammonium bromide (CTAB) and obtained pure dendritic macroporous silica (DLMSNs).
[0025] The preparation of amino-modified dendritic macroporous silica system (DLMSN-NH2) aims to provide reaction sites for subsequent coating with Bletilla striata polysaccharides. The specific process is as follows: 1g of template-removed dendritic macroporous silica (DLMSNs) was accurately weighed and placed in a round-bottom flask. 200mL of toluene was added, and the solution was heated at 80℃ until it became clear and transparent. Then, 0.2mL of 3-aminopropyltriethoxysilane (APTES) was slowly added dropwise. The mixture was kept at 80℃ and refluxed for 4h to promote the reaction between the silane coupling agent and the silanol groups on the silica surface. After the reaction, the mixture was centrifuged at 8000rpm for 5min. The precipitate was collected and washed twice with toluene to remove unreacted reagents. Finally, the sample was dried overnight at room temperature. The obtained product is amino-modified dendritic macroporous silica.
[0026] The preparation of dendritic mesoporous silica nanoparticles (DLMSN-BSP) coated with Bletilla striata polysaccharide involves an amidation reaction to immobilize the Bletilla striata polysaccharide shell onto an amino-modified core. The specific procedure is as follows: 200 mg of pre-carboxylated Bletilla striata polysaccharide powder is added to 200 mL of purified water to prepare a 1% Bletilla striata polysaccharide solution. 200 mg of N-hydroxysuccinimide (NHS) and 0.4 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) are added to the solution. The mixture is magnetically stirred for 4 hours under light-protected conditions to activate the carboxylation of the Bletilla striata polysaccharide. Amino-modified dendritic macroporous silica (DLMSN-NH2) was dispersed in an appropriate amount of solvent to form a uniform suspension. Then, the amino-modified dendritic macroporous silica (DLMSN-NH2) solution was slowly added dropwise to the activated Bletilla striata polysaccharide solution, and the mixture was magnetically stirred at room temperature in the dark for 12 hours to promote the formation of amide bonds. After the reaction was completed, the mixture was centrifuged to separate the precipitate and washed with water to remove unbound components, and finally, Bletilla striata polysaccharide-coated dendritic mesoporous silica nanoparticles (DLMSN-BSP) were obtained, which is the finished nano-delivery system.
[0027] To verify the physical properties of this nanodelivery system, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterization were performed. The specific procedures were as follows: A sample of dendritic mesoporous silica nanoparticles (DMSN) was placed on the SEM stage, and its morphology was observed under high vacuum conditions. Figure 1 As shown, the characterization results reveal that the material has uniform size and a distinct dendritic channel structure; Figure 2 As shown, transmission electron microscopy further confirmed that the material is spherical with a particle size distribution ranging from 70 to 100 nm and has ample internal dendritic channels, providing a high-capacity carrier environment for subsequent drug loading. These characterization data visually demonstrate the regular shape and uniform size of the nanoparticles, ensuring their stability during drug delivery.
[0028] Infrared spectroscopy characterization is used to analyze changes in chemical groups on the surface of materials. Specific methods include: measuring the infrared spectra of dendritic mesoporous silica nanoparticles (DMSN), amino-modified dendritic macroporous silica (DMSN-NH2), and Bletilla striata polysaccharide-coated dendritic mesoporous silica nanoparticles (DMSN-BSP), respectively. Figure 3 As shown, the detection results are displayed at a wavenumber of 798.9 cm⁻¹. -1 and 1085.16cm -1 The absorption peak at 965 cm⁻¹ corresponds to the symmetric and antisymmetric stretching vibrations of the silicon-oxygen-silicon bonds (Si-O-Si) in the silicon dioxide framework. -1 The absorption peak at 3445.49 cm⁻¹ is attributed to the bending vibration of the silanol group (Si-OH). -1 The broad peak at [0.05] represents the stretching vibration of hydroxyl groups (-OH) on the material surface; after amino modification, the peak is 3445.49 cm⁻¹. -1 The lowering and broadening of the peak at 1549.01 cm⁻¹ indicates the introduction of an amino group (-NH₂), while the peak at 1549.01 cm⁻¹... -1 The new peak at this location corresponds to the bending vibration of the amino group (-NH2); after coating with Bletilla striata polysaccharide, the peak is 3422.79 cm⁻¹. -1 The significantly enhanced and broadened hydroxyl peak reflects the hydroxyl-rich nature of Bletilla striata polysaccharide, 1630.12 cm⁻¹. -1 The new peak confirmed the formation of amide carbonyl groups, which directly proves that Bletilla striata polysaccharide was successfully bonded to the silica surface through amidation reaction.
[0029] The hemostatic performance of the nanodelivery system was tested using an in vitro dynamic coagulation assay, such as... Figure 4The specific steps, as shown, include: using sterile anticoagulated sheep blood as the test subject, and setting 25 mL of deionized water as a blank control; weighing 200 mg of dendritic mesoporous silica nanoparticles (DMSN) and 200 mg of Bletilla striata polysaccharide-coated dendritic mesoporous silica nanoparticles (DMSN-BSP) and placing them in centrifuge tubes, preheating them at 37°C for 5 min in a constant temperature incubator; adding 100 μL of sterile anticoagulated sheep blood to the sample surface and immediately adding 20 μL of 0.2 mol / L calcium chloride (CaCl₂). The l2) solution was used to simulate coagulation initiation; the mixture was then incubated at 37°C, and at different time points (1 min, 2 min, 3 min, 5 min, 6 min), phosphate-buffered saline (PBS) buffer (pH 7.4) was slowly added to the centrifuge tube to dilute the reaction solution; the sample was then placed in a shaker (37°C, 30 rpm) and shaken for 5 min to simulate blood flow dynamics; 200 μL of the supernatant was taken and the absorbance was measured at 545 nm using a UV spectrophotometer, and the test was repeated three times, with the average value used to calculate the coagulation index. The experimental results showed that the coagulation index (BCI) of the dendritic mesoporous silica nanoparticles (DMSN-BSP) group coated with Bletilla striata polysaccharide was significantly lower than that of the uncoated group. This indicates that the nanodelivery system activates the adenosine diphosphate receptor signaling pathway by activating platelet membrane receptors and protein kinase C receptors, promoting platelet deformation, aggregation, and secretion, thereby achieving a strong hemostatic function.
[0030] Antimicrobial performance testing is used to evaluate the effectiveness of nanodelivery systems in anti-infective applications, such as... Figure 5 As shown, the specific method is as follows: Take 500 μL of the activated Escherichia coli suspension (concentration of...). An equal volume of dendritic mesoporous silica nanoparticles (DMSN) was added to the control group (CFU / mL), and another 500 μL of the same bacterial suspension was added to an equal volume of Bletilla striata polysaccharide-coated dendritic mesoporous silica nanoparticles (DMSN-BSP) as the experimental group. Both were incubated at 37°C for 24 h. The bacterial suspension was then serially diluted 10-fold, and 100 μL was evenly spread onto an agar plate and incubated at 37°C for 18 h. An agar plate containing no sample was used as a blank control. The antibacterial rate was calculated by counting the colonies on the plates. The results showed that the experimental group had an antibacterial rate of 29.50% against Escherichia coli and 14.39% against Staphylococcus aureus, confirming that the nanodelivery system effectively inhibits the growth of common pathogens after drug release.
[0031] The beneficial effects of this invention are as follows: (1) A nano-delivery system is constructed using dendritic mesoporous silica loaded with therapeutic drugs as the core and Bletilla striata polysaccharide as the shell to achieve the time-sequence control effect of hemostasis before treatment and exert the synergistic effect of anti-infection and tissue repair. (2) By using a two-step method (first step to form a basic mesoporous structure, and second step to construct dendritic channels through the action of chlorobenzene and TEOS), the specific surface area and pore volume are increased, providing a high-capacity carrier environment for drug loading, which helps to deliver drugs efficiently. (3) Amino modification of dendritic macroporous silica provides reaction sites, which facilitates the stable fixation of the shell of Bletilla striata polysaccharide; (4) The nanodelivery system has excellent hemostatic properties and promotes platelet activation and aggregation; (5) After the nano-delivery system releases the drug, it effectively inhibits the growth of pathogens and enhances the anti-infection effect.
[0032] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A method for preparing a nanodelivery system, characterized in that, include: Dendritic mesoporous silica nanoparticles were prepared as core carriers; amino functional groups were modified on the dendritic mesoporous silica nanoparticles to provide reaction sites. The carboxyl groups of Bletilla striata polysaccharide are activated to enable it to bind. Amino-modified dendritic mesoporous silica nanoparticles are mixed and reacted with the activated Bletilla striata polysaccharide to form a core-shell nanodelivery system with dendritic mesoporous silica as the core and Bletilla striata polysaccharide as the shell, thereby achieving the time-sequence control function of hemostasis followed by treatment.
2. The method for preparing the nanodelivery system as described in claim 1, characterized in that, In the preparation of dendritic mesoporous silica nanoparticles, a surfactant template-directed method is used, in which organic solvents are added to regulate the pore morphology and form a dendritic pore structure to increase the specific surface area and pore volume.
3. The method for preparing the nanodelivery system as described in claim 1, characterized in that, The modification of amino functional groups was carried out by heating and refluxing in an organic solvent using a silane coupling agent, so that the amino groups were stably bound to the surface of dendritic mesoporous silica.
4. The method for preparing the nanodelivery system as described in claim 1, characterized in that, The carboxyl groups of Bletilla striata polysaccharide were activated using carbodiimide and hydroxysuccinimide as activators, and the mixture was stirred under light-protected conditions to promote carboxyl activation.
5. The method for preparing the nanodelivery system as described in claim 1, characterized in that, The mixing reaction was carried out at room temperature in the dark. Stirring induced the formation of amide bonds between amino and carboxyl groups, thus achieving a firm coating of Bletilla striata polysaccharide shell.
6. The method for preparing the nanodelivery system as described in claim 1, characterized in that, The preparation of dendritic mesoporous silica nanoparticles includes a step of removing the template agent and eliminating surfactant residues by high-temperature calcination.
7. The method for preparing the nanodelivery system as described in claim 1, characterized in that, After the reaction is complete, unreacted components are removed through separation and washing to obtain a pure core-shell structured nanodelivery system.
8. The method for preparing the nanodelivery system as described in claim 1, characterized in that, The synthesis of dendritic mesoporous silica nanoparticles employs a two-step method to construct pores. The first step forms a basic mesoporous framework, and the second step expands the pores using organic solvents to form a dendritic structure.
9. A nanodelivery system, characterized in that, Prepared using the preparation method described in any one of claims 1-8, the nanodelivery system comprises a dendritic mesoporous silica core loaded with therapeutic drugs and a Bletilla striata polysaccharide shell, forming a core-shell structure. The shell is used for immediate hemostasis, and the core is used for sustained drug release therapy.
10. An application of a nanodelivery system, characterized in that, The nanodelivery system as described in claim 9 is applied to the field of wound repair to achieve hemostasis, antibacterial and tissue repair functions.