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Slow-release gel drug delivery system for postoperative intracavitary chemotherapy/immune co-treatment as well as preparation method and application of sustained-release gel drug delivery system

A sustained release and drug delivery technology, applied in the field of medicine, can solve the problems of unfavorable clinical transformation application, poor prognosis, and insufficient survival rate

Active Publication Date: 2022-02-18
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Glioma is highly malignant, the treatment effect is not ideal, the prognosis is extremely poor and the mortality rate is extremely high, the median survival time is less than 18 months, and the 5-year survival rate is less than 3%.
However, CpG can effectively activate the glioma immune response only if it is continuously stimulated in the brain, and the half-life of CpG in the cerebrospinal fluid is only 1 hour. Therefore, the current use of CpG in glioma immunotherapy must be administered through repeated intracerebroventricular injections or intratumoral injections , this way of administration is not conducive to clinical translation

Method used

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  • Slow-release gel drug delivery system for postoperative intracavitary chemotherapy/immune co-treatment as well as preparation method and application of sustained-release gel drug delivery system
  • Slow-release gel drug delivery system for postoperative intracavitary chemotherapy/immune co-treatment as well as preparation method and application of sustained-release gel drug delivery system
  • Slow-release gel drug delivery system for postoperative intracavitary chemotherapy/immune co-treatment as well as preparation method and application of sustained-release gel drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] (1) PSNPs, NPs PTX and PNP PTX Preparation and synthesis

[0067] Weigh 5mg of PTX-SS-C 18 Dissolve in 0.5mL of absolute ethanol to obtain the organic phase. Slowly drop the organic phase into 10mL of pure water (water phase) under constant stirring (700rpm) with a micro syringe at room temperature. The residual organic solvent was removed by rotary evaporation for 5 min, and finally filtered through a 0.45 μm, 0.22 μm microporous membrane to obtain self-assembled PTX prodrug nanoparticles (PSNPs). MeO-PEG 2000 -DSPE and Pep-PEG 2000 -DSPE was dissolved in water respectively, and mixed with the PSNPs prepared by the above method (MeO-PEG 2000 -DSPE or Pep-PEG 2000 -DSPE / PSNPs=20 / 100,w / w), resulting in non-targeting nanoparticles (NP PTX ) and targeted nanoparticles (PNP PTX ).

[0068] Will PSNPs, NP PTX and PNP PTX After diluting to appropriate multiples with deionized water, the particle size was measured with a Malvern laser particle size analyzer Zetasize...

Embodiment 2

[0080] Example 2PNP PTX and MNP CpG in vitro release of

[0081](1) According to the preparation method of the PTX nanoparticles in the example, the in vitro release behavior of PTX in the nanoparticles was investigated by ultrafiltration centrifugation. Take an appropriate amount of the prepared nanoparticle solution, dilute it to 30mL with release medium, put it in a 50ml EP tube, and the total amount of PTX is 15μg, so as to ensure that the drug release is carried out under the sink condition. The release media were HAc-NaAc buffer (0.04M, pH 5.6) containing 10mM GSH and 0.5% Tween-80 to simulate the tumor microenvironment, and cerebrospinal fluid (CSF, pH 5.6) containing 1 μM GSH and 0.5% Tween-80, respectively. 7.4) to simulate the microenvironment of cerebrospinal fluid. Put the diluted nanoparticles into a 37°C constant temperature shaker (150rpm), take out three groups of samples in parallel at 0.25, 0.5, 0.75, 1, 2, 3, 4, 8, and 12h, and immediately transfer them t...

Embodiment 3

[0084] will PNP PTX and MNP CpG Add to the temperature-sensitive gel solution, the volume ratio of the three is 1:1:8, PNP PTX and MNP CpG The concentration in the temperature-sensitive gel solution is 10%, and the mixture is evenly stirred to obtain the drug-loaded nanogel PNP PTX &MNP CpG @Gel; a temperature sensitive gel solution is prepared by weighing out an amount of PLGA 1750 –PEG 1500 –PLGA 1750 , uniformly dispersed in distilled water, and placed at room temperature for 24 hours to fully swell to obtain PLGA 1750 –PEG 1500 –PLGA 1750 The concentration is 10-30% (w / v) gel aqueous solution, and the concentration is 20%.

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Abstract

The invention discloses a sustained-release gel drug delivery system for postoperative intracavitary chemotherapy / immune co-treatment as well as a preparation method and application of the sustained-release gel drug delivery system. The sustained-release drug delivery system is a drug delivery system prepared by embedding a PTX prodrug targeting nanoparticle and a CpG targeting polymer nanoparticle into a temperature-sensitive gel material serving as a skeleton, wherein the temperature-sensitive gel material is a poly(lactic-co-hydroxyacetic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) triblock copolymer. According to the invention, chemical treatment and immunotherapy are combined and are taken together to kill residual glioma cells and play a role in synergistic treatment, and the purposes of slowly releasing drugs and treating glioma in situ can also be achieved.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the construction of an in-situ slow-release gel drug delivery system and the application of chemotherapy / immunity synergistic therapy in the postoperative cavity of glioma. Background technique [0002] Glioma is the most common primary central nervous system (Central nervous system, CNS) tumor, accounting for about 80% of all primary CNS tumors. Glioma has a high degree of malignancy, unsatisfactory treatment effect, extremely poor prognosis and high mortality. The median survival time is less than 18 months, and the 5-year survival rate is less than 3%. At present, the clinical treatment methods for glioma mainly include surgery, postoperative chemotherapy and radiotherapy, and in most cases, surgical resection is the first choice. However, most of the gliomas grow in the important functional areas of the brain, and they grow infiltratively, without a clear bounda...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/34A61K31/337A61K39/39A61K9/51A61K47/64A61P35/00
CPCA61K9/06A61K47/34A61K9/0024A61K31/337A61K39/39A61P35/00A61K9/5153A61K47/64A61K2039/55561A61K2300/00
Inventor 辛洪亮叶璐王晓琪
Owner NANJING MEDICAL UNIV
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