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Copolymerization micelle drug-loading nanoparticle and application thereof

A drug-loaded nanometer and micelle technology, which can be used in antitumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of complex preparation process, high cost, and poor tumor cell killing effect.

Inactive Publication Date: 2019-03-12
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In the prior art, the nano-drug delivery system that co-delivers chemotherapeutic drugs and gene drugs is generally delivered by liposomes. On the one hand, in the prior art, liposomes are used as carriers for co-loading chemotherapeutic drugs and gene drugs, and the preparation process is relatively complicated. , and the cost is high. On the other hand, although liposomes have a high phagocytosis rate in vitro, liposomes are relatively soft and cannot penetrate the tumor matrix to reach cells, making their tumor cell killing effect poor.

Method used

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  • Copolymerization micelle drug-loading nanoparticle and application thereof
  • Copolymerization micelle drug-loading nanoparticle and application thereof
  • Copolymerization micelle drug-loading nanoparticle and application thereof

Examples

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Effect test

Embodiment 1

[0028] A copolymerized micelle drug-loaded nanoparticle disclosed in Example 1, which comprises an uncharged hydrophilic polymer chain block, an uncharged hydrophobic polymer chain block, and a cationic polymer chain block A block copolymer, the non-charged hydrophilic polymer chain block and the cationic polymer chain block both ends of the non-charged hydrophobic polymer chain block through chemical bonds, the cationic polymer The chain blocks are grafted with lipid ligands, wherein the uncharged hydrophilic polymer chain block is polyethylene glycol, and the uncharged hydrophobic polymer chain is ε-caprolactone, and the cationic The polymer chain block is polylysine, and the lipid ligand is cholesterol, forming a three-block copolymer poly(ethylene glycol)-poly(ε-caprolactone)-poly(L-lysine) from The assembled micellar system nano drug-loaded particle is recorded as mPEG-bPCL-b-PLL / Chol, and its chemical equation is as follows:

[0029]

[0030] As an improved specific ...

Embodiment 2

[0032] A method for preparing copolymerized micelles drug-loaded nanoparticles disclosed in Example 2,

[0033] Preparation of mPEG-b-PCL-b-PLL polymer: Dissolve appropriate amount of mPEG and ε-CL monomer in toluene, blow nitrogen gas, add catalyst stannous zincate, stir and react at 120°C for 24 hours under nitrogen protection, and obtain mPEG-b-PCL-OH; Take 3g dry mPEG-b-PCL-OH powder, dissolve it in 15ml chloroform, add TEA and MsCl, stir and react at 0℃ for 12 hours, extract and lyophilize, redissolve in DMF solvent, add Diazonium salt, reaction at room temperature for 48 hours to obtain mPEG-b-PCL-N 3;mPEG-b-PCL-N 3 with propargyl-PZLL, CuCl 2 (catalyst), NaVc was dissolved in DMF, under nitrogen protection, microwave reaction was used for 30 minutes to obtain mPEG-b-PCL-b-PZLL; the obtained product was added with TFA and hydrogen bromide, and reacted at 0°C for 40 minutes to obtain the final mPEG- b-PCL-b-PLL polymer. The obtained final product was extracted with et...

Embodiment 3

[0036] Example 3 discloses the loading method of doxorubicin and siRNA loading the above-mentioned copolymerized micellar drug-loaded nanoparticles. Dissolve mPEG-bPCL-b-PLL / Chol and doxorubicin in 1ml of tetrahydrofuran, and stir at 20°C for 1 Hours, self-assembled to form nanomicelles, recorded as PD; add 1ml double distilled water dropwise, continue to stir for 1 hour, extract micelles, remove THF; add 1ml siRNA solution to form co-loaded doxorubicin and siRNA micelles drug-loaded nanoparticles , recorded as PD / siRNA.

[0037] The micellar nano drug-loaded particles prepared according to the above method can selectively release siRNA and doxorubicin in an acidic environment. The results of the release experiment showed that under neutral conditions (pH=7.4), the cumulative release of doxorubicin / siRNA and doxorubicin was not much different, and the cumulative release amount was only 50%. While under acidic conditions (pH=5.5), the cumulative release of doxorubicin is 80%. ...

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Abstract

The invention discloses a copolymerization micelle drug-loading nanoparticle. The copolymerization micelle drug-loading nanoparticle is a block copolymer comprising a discharged hydrophilic polymer chain block, a discharged hydrophobic polymer chain block and a cationic polymer chain block. The discharged hydrophilic polymer chain block and the cationic polymer chain block are positioned at two ends of the discharged hydrophobic polymer chain block through chemical bonds. The cationic polymer chain block is grafted with a lipid ligand. The nano drug-loading particle as a triblock copolymer self-assembled micelle system is capable of realizing co-transmission of siRNA and a chemotherapy drug. A triblock copolymer is amphipathic, and can be self-assembled into the micelle nanoparticle. Preparation cost is low and preparation is convenient. A hydrophilic part is capable of reinforcing circulation time. The discharged hydrophobic polymer chain block is used for wrapping adriamycin so as toform a hydrophobic kernel. The cationic polymer chain block carries positive charge, so that the negative charge siRNA can be carried. Cholesterol is connected to the cationic polymer chain block, sothat efficiency of endocytosis is improved.

Description

technical field [0001] The invention relates to a copolymerized micelle drug-loaded nanoparticle and its application field. Background technique [0002] Small interfering RNA (small interfering RNA, siRNA) is an effector molecule of RNA interference (RNA interfering, RNAi). Specially designed siRNA can target and silence specific messenger RNA (message RNA, mRNA), causing related protein degradation to inhibit cell proliferation and tumor growth. Therefore, siRNA has broad application potential in the treatment of human diseases including tumors. But at the same time, there are still some problems in the application of double-stranded siRNA, including poor pharmacokinetics due to easy degradation by enzymes, negative surface charge is not conducive to cell uptake, and lack of cell targeting leads to large side effects. Therefore, in order to realize the clinical application of RNAi, it is necessary to develop specific tissue-targeted, low-toxicity and high-efficiency siRN...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K47/34A61K31/704A61K31/7105A61P35/00
CPCA61K9/1075A61K31/704A61K31/7105A61K47/34A61P35/00A61K2300/00
Inventor 沈建良钱宇娜齐若谷
Owner WENZHOU MEDICAL UNIV
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