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Polylactic acid-polypeptide micelle and application thereof

A technology of polylactic acid and micelles, which is applied in the field of biomedicine, can solve the problems of changing the structure and function of nucleic acid and drugs, affecting the therapeutic effect and safety, and having no therapeutic effect, so as to promote cell uptake, reasonable particle size and potential , the effect of avoiding side effects

Active Publication Date: 2021-03-16
宝龙药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the nucleic acid in the drug delivery system only self-assembles as the backbone of the drug delivery system to form a drug-containing nanocarrier, which has no therapeutic effect, and the drug delivery system changes the structure and function of the nucleic acid and the drug, resulting in poor therapeutic effect and safety. affected

Method used

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  • Polylactic acid-polypeptide micelle and application thereof
  • Polylactic acid-polypeptide micelle and application thereof
  • Polylactic acid-polypeptide micelle and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Synthesis of Targeted Co-delivery of Chemotherapeutic Drugs and Gene Drug Carrier PHRD

[0044] ① Protect polylactic acid (PLA) with TBDMS for hydroxyl groups, activate with dicyclohexylcarbodiimide (DCC) and HOBt, remove dicyclohexylurea (DCU) by filtration, add H-His(Trt)-OH to react overnight to obtain TBDMS-polylactic acid-His(Trt)-OH;

[0045] ②Deprotect Fmoc-Arg(Pbf)-Wang Resin with Pip / DMF for 30min, and put in amino acid (AA), tetramethyluronium hexafluorophosphate (HBTU) and N-methylmorpholine (NMM) in an equivalent ratio, Add an appropriate amount of DMF, and react with nitrogen gas for 30 minutes, and the resin sample is transparent when ninhydrin is detected;

[0046] ③ Repeat step ② until the sequence is coupled to the penultimate amino acid;

[0047] ④ Add TBDMS-polylactic acid-His(Trt)-OH, HBTU and NMM to the reactor in proportion, couple for 2 hours, take a sample of the resin and detect it with ninhydrin, wash it with methanol, drain the res...

Embodiment 2

[0050] Example 2 Characterization of targeted co-delivery of chemotherapeutic drugs and gene drug carrier PHRD

[0051] (1) Infrared spectrum identification

[0052] Take 1~2mg of solid dry samples of PHR and PHRD, grind them thoroughly in an agate mortar, add 400mg of dry KBr, and continue to grind until completely mixed, the particle diameter is about 2μm; take 100mg of the mixture and evenly spread it on a clean pressure film Inside, on the tablet press under the pressure of 29.4Mpa, press for 1min to make a transparent sheet; install the transparent sheet on the sample holder, place it at the sample cell of the spectrophotometer, and measure it from 4000cm -1 Sweep up to 400cm -1 .

[0053] It can be known from the structure of DR5 that there are free hydroxyl groups (3700cm -1 ~3500cm -1 ), free amino (3500cm -1 ~3300cm -1 ), associative amino group (3450cm -1 ~3200cm -1 ), carboxylic acid group (1900cm -1 ~1650cm -1 ), benzene ring (3000cm -1 , 1680cm -1 ~150...

Embodiment 3

[0057] Example 3 Construction of polylactic acid-polypeptide micelles co-loading DTIC and miRNA-34a

[0058] In this example, based on the targeted co-delivery of chemotherapeutic drugs and the gene drug carrier PHRD, the phacoemulsification method was used to prepare polypeptide micelles co-loaded with the chemotherapeutic drug dacarbazine (DTIC) and the gene drug miRNA-34a. The steps are as follows:

[0059] (1) Dissolve 3mg DTIC in 3mL methanol to prepare a 1mg / mL solution;

[0060] (2) Weigh 5 mg of PHRD, dissolve it in deionized water, and prepare a 1 mg / mL solution, add 3 mL of DTIC solution to the PHRD solution drop by drop, and ultrasonicate under ice bath conditions with a power of 100 W and a time of 30 s. 2 times;

[0061] (3) Quickly transfer the emulsified mixed solution to a magnetic stirrer for rapid stirring overnight, remove the methanol in the solution and collect the mixed solution, remove unencapsulated DTIC with a microporous filter membrane with a pore s...

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Abstract

The invention provides a polylactic acid-polypeptide micelle and application thereof, the polylactic acid-polypeptide micelle is formed by self-assembly of an amphiphilic polylactic acid-polypeptide polymer, and the amphiphilic polylactic acid-polypeptide polymer comprises a hydrophilic polypeptide containing arginine and hydrophobic polylactic acid for providing an assembly driving force; the hydrophilic polypeptide forms a shell of the polylactic acid-polypeptide micelle, and the hydrophobic polylactic acid forms an inner core of the polylactic acid-polypeptide micelle; and the amphiphilic polylactic acid-polypeptide polymer is also connected with an aptamer for targeting tumor cells. The polylactic acid-polypeptide micelle disclosed by the invention is stable in structure, the tumor treatment drug is entrapped in the hydrophobic core, the polypeptide aptamer is used for targeting tumor cells, depolymerization occurs when reaching an acidic tumor environment, and the entrapped drug is slowly released, so that the polylactic acid-polypeptide micelle is high in safety and low in toxicity, and has important significance in the field of combined treatment of tumors.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to a polylactic acid-polypeptide micelle and an application thereof. Background technique [0002] Nanocarriers are very effective drug delivery vehicles and have been widely used in disease treatment. The nanostructure enhances the permeability and retention effect (EPR) of the nanocarriers, enabling the nanocarriers to passively accumulate in tumor tissues and have a synergistic effect with the drug delivery, resulting in a significantly enhanced antitumor effect. [0003] Currently, nanocarriers are usually loaded with one or a class of drugs, and Tai et al. reported a cationic reduction reaction carrier based on disulfide-crosslinked polylactic acid containing arginine and histidine, which can be effectively delivered in vitro and in vivo. Gene medicine (Tai Z, Wang X, Tian J, Gao Y, Zhang L, Yao C, Wu X, Zhang W, Zhu Q, Gao S: Biodegradable stearylated peptide with internal ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K45/00A61K47/42A61K47/62A61P35/00B82Y5/00
CPCA61K9/1075A61K47/42A61K47/62A61K45/00A61P35/00B82Y5/00
Inventor 丁宝月李明娟张洁武鑫詹淑玉孙李丹敖雷吕晓庆刘国强郑永霞吴兆勇宫春爱蒋治江
Owner 宝龙药业有限公司
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