Tri-block polymer micelle, preparation method and application

A polymer and tri-block technology, applied in the direction of drug combination, pharmaceutical formulation, genetic material components, etc., can solve problems such as difficult to degrade, high cytotoxicity, etc., to achieve enhanced penetration and retention, good biocompatibility and biological Effect of degradability and excellent tissue permeability

Active Publication Date: 2014-10-15
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this type of polymer is difficult to degrade in cells and has high cytotoxicity, which limits its application to a certain extent.

Method used

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  • Tri-block polymer micelle, preparation method and application
  • Tri-block polymer micelle, preparation method and application
  • Tri-block polymer micelle, preparation method and application

Examples

Experimental program
Comparison scheme
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Embodiment 1

[0042] This example provides a doxorubicin-loaded micelle of N-succinyl chitosan-poly-L-lysine-pallitic acid triblock polymer.

[0043] See attached figure 1 , which is a schematic diagram of the synthetic route of the N-succinyl chitosan-poly-L-lysine-soft fatty acid triblock polymer provided by the present invention. In this embodiment, the specific synthesis method includes the following steps:

[0044] 1. Synthesis of N-succinyl chitosan-poly-L-lysine (NSC-PLL)

[0045] Dissolve 0.4 g of NSC in 25 mL of distilled water and stir to form a solution. Put 0.32 g PLL, 0.192 g EDC·HCl and 0.057 g NHS into the above reaction solution respectively, 1.1 mol.L -1 Adjust pH to 5.6 with HcL, magnetically stir the reaction liquid, react at room temperature for 7 2 h, place in a dialysis bag (MWCO=3 500), dialyze with distilled water for 3 days, filter and freeze-dry to obtain NSC-PLL.

[0046] 2. Activation of palmitic acid (PA)

[0047] 0.128 g of soft fatty acid was added to 25...

Embodiment 2

[0058] This embodiment provides a kind of N-succinyl chitosan-poly-L-lysine-soft fatty acid triblock polymer loaded with siRNA micelles, the specific steps of preparation include: preparing N -Succinyl chitosan-poly-L-lysine-soft fatty acid triblock polymer, dissolve it in 5 ml deionized water to prepare 1 mg.mL -1 blank micellar solution. Incubate blank micelles with siRNA (N / P=20-40) at 37°C with shaking for 30 min to obtain N-succinyl chitosan-poly-L-lysine-soft fatty acid triblock polymer-loaded siRNA gel bundle.

[0059] The ability of the N-succinyl chitosan-poly-L-lysine-pallitic acid triblock polymer-loaded siRNA micelles to bind siRNA was determined by agarose gel electrophoresis. Add 17 μL DEPC-treated water, 1 μL, 2 μL, 4 μL, 8 μL, 16 μL micellar solution to 6 EP tubes of RNase, and make up to 18 μL for each group with DEPC-treated water . Mix the solutions in each EP tube thoroughly and let stand at room temperature for 30 min. Take 15 μL and add 3 μL 6×loading...

Embodiment 3

[0063] In this example, N-succinyl chitosan-poly-L-lysine-pallitic acid triblock polymer was prepared to co-transport doxorubicin and siRNA micelles. The N-succinyl chitosan-poly-L-lysine-soft fatty acid triblock polymer prepared by the technical scheme of Example 1 was dissolved in 5 ml deionized water to obtain 1 mg.mL -1 The blank micelle solution of the doxorubicin hydrochloride was dissolved with an appropriate amount of DMSO solution, and triethylamine with a molar ratio of 1:2 to the doxorubicin hydrochloride was added for desalting treatment, and then the desalted doxorubicin was slowly added dropwise to the above blank In the micellar solution, the final concentration of the drug was 0.2 mg.mL -1 ; Sonication for 30 min, magnetic stirring for 2 h, and then placed in a dialysis bag for dialysis for 4 h, changing distilled water every 1 h, and filtering the dialysate with a 0.45 μm microporous membrane to obtain a doxorubicin-loaded micelle sample. Incubate drug-loaded...

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Abstract

The invention discloses a tri-block polymer micelle, a preparation method and an application. The tri-block polymer micelle is formed by self-assembly of a tri-block polymer, takes fatty acid as a core, takes poly-L-lysine as a middle layer and takes N-succinyl chitosan as a casing to be self-assembled into the micelle; the hydrophobic core is used for entrapping hydrophobic anti-cancer drugs, the middle layer carrying positive charges is used for adsorbing genes, the micelle can release the supported genes after being degraded, and the hydrophilic casing is used for reducing the toxicity of the poly-L-lysine and prolonging the blood circulation time of the poly-L-lysine after system administration. According to the micelle, the genes are adsorbed after particles are formed, so that the control on sizes of the micelle particles and large-scale preparation of the micelle particles are facilitated; the delivery system can transfect the genes to enter target cells and regulate expression of interest protein in the presence of serum and has the good biocompatibility. The micelle can support the hydrophobic anti-cancer drugs and genes simultaneously and play a synergistic anti-tumor role.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an N-succinyl chitosan (NSC)-poly-L-lysine (PLL)-fatty acid (FA) triblock polymer micelle, a preparation method and application thereof. Background technique [0002] With the sharp increase in the morbidity and mortality of malignant tumors, the treatment of tumors has become a global problem that needs to be solved urgently. However, in the treatment of tumor diseases, the effect of drug therapy is not good, most chemotherapy drugs have poor water solubility and lack of selectivity for tumor sites (Cheong I, Huang X, Bettegowda C, Diaz LAJ, Kinzler KW, Zhou SB, et al. A bacterial protein enhances the release and efficacy of liposomal cancer drugs. Science. 2006; 314:1308–1311), and with the widespread use of antineoplastic drugs, most tumor cells develop multidrug resistance, which has become a key factor for the failure of tumor chemotherapy One of (Gullotti E, Yeo Y....

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K47/36A61K48/00A61P35/00A61K45/00A61K31/704
Inventor 张学农张春歌
Owner SUZHOU UNIV
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