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Preparation method of multilevel slow-release drug-loaded short nano-fibers

A drug-loaded nanometer and short fiber technology, which is applied in the direction of pharmaceutical formulation, fiber treatment, and medical preparations of non-active ingredients, etc., can solve the problems of reducing the utilization rate of drugs, secondary harm to patients, etc., and achieve the goal of overcoming multi-drug resistance , low cost, and broad research prospects

Active Publication Date: 2019-09-06
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, electrospun nanofibers are usually used in the form of membranes, which can only be implanted or administered externally, which is likely to cause secondary harm to patients or reduce the utilization rate of drugs

Method used

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  • Preparation method of multilevel slow-release drug-loaded short nano-fibers
  • Preparation method of multilevel slow-release drug-loaded short nano-fibers
  • Preparation method of multilevel slow-release drug-loaded short nano-fibers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] (1) 830.8 mg Mg (NO 3 ) 2 ·6H 2 O and 603.8 mg Al (NO 3 ) 3 ·9H 2 O was dissolved in 50 mL of ultrapure water, and the two compounds were fully dissolved by vigorous stirring at 25 °C for 20 min. Mix the two solutions well. Fill with nitrogen and drive out oxygen for 5 times, and then add 15 mL of 1M NaOH solution in a nitrogen atmosphere to adjust the pH of the solution to 9.5. Stir vigorously for 48 h at 25° C. to fully react. Collect the reacted solution in a centrifuge tube, set the rotating speed to 6000 rpm, and set the centrifugation time to 10 min, and the obtained white precipitate is LDH. Add an appropriate amount of ultrapure water and use a vortex shaker to disperse the precipitate evenly, perform ultrasonic washing, and then set the rotation speed to 6000 rpm for 10 min of centrifugation. Repeat the operation 3 times to obtain a pure LDH precipitate. Vacuum freeze-drying to obtain LDH nanoparticles.

[0045] (2) Dissolve 20.3 mg DOX and 10.3 mg LDH ...

Embodiment 2

[0049] The present invention adopts scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), infrared spectroscopy (FTIR), ultraviolet-spectrophotometer (UV-Vis), blood coagulation experiment, cell viability analysis ( CCK-8 test), laser confocal microscope to characterize the morphology of LDH and multi-stage slow-release drug-loaded nano short fibers prepared by the present invention, the long-term multi-stage drug release effect of short fibers and the effect of short fibers in drug-resistant cancer cells application potential.

[0050] Scanning Electron Microscope Test:

[0051] Scanning electron microscopy was used to characterize the LDH obtained in step (1) of Example 1 and the DOX@LDH / α-TOS / PLGA short fibers obtained in step (5). The SEM results of LDH are as follows figure 2 As shown in a-b, the diameter of LDH is 76±18.9nm, which is relatively uniform hexagonal or disc shape. The SEM results of DOX@LDH / α-TOS / PLGA short ...

Embodiment 3

[0059] In vitro release kinetic testing

[0060] The drug release from short fibers in buffer solutions with different pH at different time points was measured using a UV-spectrophotometer (UV-Vis). 5 mg of DOX / PLGA, α-TOS / PLGA and DOX@LDH / α-TOS / PLGA short fibers were added to 1 mL of PBS buffer with pH=7.4, 6.8, and 5.5, respectively, and dispersed uniformly by ultrasonic wave. In the bag, put the dialysis bag filled with the material into a 50 mL centrifuge tube, add 9 mL of PBS buffer corresponding to pH, and put it into a constant temperature shaker for drug sustained release experiments. In the first 3 days, take the solution at 1, 2, 4, 8, 16, 24, 48, and 72 hours in sequence, take the solution every two days from the 4th day to the 20th day, and take the solution every five days from the 20th day to the 60th day. . Take 1 mL each time, and add 1 mL of PBS buffer corresponding to pH to the centrifuge tube. Measure the absorbance of DOX@LDH / α-TOS / PLGA short fiber solut...

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Abstract

The invention relates to a preparation method of multilevel slow-release drug-loaded short nano-fibers. According to the method, layered double hydroxides (LDH) loaded doxorubicin (DOX) serving as ananti-cancer drug and alpha-tocopherol succinate (alpha-TOS) serving as a P-gp inhibitor are mixed into polylactic acid-glycolic acid copolymer (PLGA) spinning solution, and electrostatic spinning andhomogeneous treatment are implemented to obtain the fibers. The multilevel slow-release double medicine carrying short nano-fibers are built by the aid of organic and inorganic double carriers, multilevel release of the anti-cancer drug and the P-gp inhibitor in materials can be achieved in tumor micro-acidic environments, multi-drug resistance of cancer cells is overcome, the double-carrier nano-fibers lengthen release paths of the drugs, slow release of the anti-cancer drug is achieved, and a novel method is provided for long-term and effective treatment of drug-resistant tumors.

Description

technical field [0001] The invention belongs to the field of drug carriers, and in particular relates to a preparation method of multi-level slow-release drug-loaded nano-short fibers. Background technique [0002] Cancer is one of the leading causes of death, and the World Health Organization (WHO) estimates that 13.13 million deaths will be related to cancer in 2030. Currently, cancer treatment options mainly include surgery, chemotherapy, radiation therapy, and combinations of these methods. Chemotherapy, as one of the most commonly used treatments, mainly causes the death of rapidly growing and dividing cancer cells by interfering with DNA synthesis and mitosis. Many primary tumors and metastatic lesions respond well initially to chemotherapy, but tumors often recur and develop drug resistance. Drug resistance is mainly reflected in the insensitivity of cancer cells to treatment, which is a key factor leading to the failure of anti-tumor chemotherapy. Because these tu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/704A61K31/355A61K9/00A61K47/02A61K47/34A61P35/00D01D5/00
CPCA61K9/0019A61K31/355A61K31/704A61K45/06A61K47/02A61K47/34A61P35/00D01D5/003D01D5/0061A61K2300/00
Inventor 史向阳马玉培肖云超
Owner DONGHUA UNIV
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