Polyester peptide vesicle with inner membrane with negative charges and preparation method and application of polyester peptide vesicle

A technology of polyester and vesicles, which is applied in the fields of polymer materials and applied chemistry, can solve problems such as low protein encapsulation efficiency, and achieve the effects of high protein encapsulation capacity, good application prospects and simple preparation method.

Active Publication Date: 2019-01-04
SUZHOU UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the encapsulation efficiency of conventional polymersomes for proteins is very low

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Polyester peptide vesicle with inner membrane with negative charges and preparation method and application of polyester peptide vesicle
  • Polyester peptide vesicle with inner membrane with negative charges and preparation method and application of polyester peptide vesicle
  • Polyester peptide vesicle with inner membrane with negative charges and preparation method and application of polyester peptide vesicle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Polyethylene glycol-b-poly(2-aminohexadecanoic acid)-b-poly(β-benzyl-L-aspartic acid) (PEG-b-PAPA-b-PBLA) three Synthesis of Block Copolymers

[0038] The PEG-b-PAPA-b-PBLA triblock copolymer was prepared in the form of PEG-NH in DMF solution under nitrogen 2 2-aminohexadecanoic acid-N-carboxylate anhydride monomer (APA-NCA) and β-benzyl-L-aspartic acid-N-carboxylate anhydride monomer (BLA- NCA) prepared by ring-opening polymerization. The specific synthesis steps are as follows: under a nitrogen atmosphere, a DMF solution of 10 mL of APA-NCA (0.52 g, 1.76 mmol) was rapidly added to PEG-NH 2 DMF (2 mL) solution, after reacting at 35° C. for 72 hours, the second monomer BLA-NCA was added, and then the reaction was continued for 72 hours. After the reaction, the reaction solution was precipitated in 20 times excess glacial ether for several times, and finally vacuum-dried to obtain a white solid product. Yield: 83%.

[0039] The NMR spectrum of PEG-b-PAPA-...

Embodiment 2

[0040] Embodiment 2: Synthesis of PEG-b-PAPA-b-PAsp copolymer

[0041]PEG-b-PAPA-b-PAsp triblock copolymer was obtained by deprotecting PEG-b-PAPA-b-PBLA in HBr. The specific steps are as follows: HBr (33wt.% HOAc, 0.3mL, 1.66mmol) was added to a solution of PEG-b-PAPA-b-PBLA (0.3g, 0.015mmol) in trifluoroacetic acid (3mL) and reacted at 0°C 2 hours. After the reaction was finished, precipitation was repeated several times with excess glacial ether, and finally vacuum-dried to obtain a white solid product. Yield: 80%.

[0042] The NMR spectrum of PEG-b-PAPA-b-PAsp is attached figure 2 , 1 H NMR (600MHz, CDCl 3 / CF 3 COOH(9 / 1,v / v), figure 2 ,δ):4.50(1H,-COCHNH-),3.72(4H,-OCH 2 CH 2 O-),3.47(3H,-OCH 3 ),2.99(2H,-COCH 2 -),1.82(2H,-CH(NH)CH 2 CH 2 -),1.24(24H,-CH 2 (CH 2 ) 12 CH 3 ),0.85(3H,-CH 2 CH 3 ).

[0043] Table 1. Characterization of PEG-b-PAPA-b-PBLA triblock copolymers

[0044]

[0045] a Depend on 1 Calculated by H NMR. b Measured by GPC (m...

Embodiment 3

[0046] Example 3: Preparation of Polylipopeptide Vesicles with Asymmetric Membrane Structure and Determination of its Critical Aggregation Concentration (CAC)

[0047] cRGD-modified polylipopeptide vesicles (cRGD-CLP) were prepared by solvent displacement method. The brief steps are as follows: 0.2 mL of 2 mg / mL containing 20 mol.% cRGD-PEG-b-PAPA (M n =6.0-11.3kg / mol) and 80mol.% mPEG-b-PAPA-b-PAsp (M n =5.0-10.1-1.4kg / mol) was added dropwise to 0.8mL of PB buffer medium (10mM, pH 7.4), and then dialyzed in PB for 8 hours, changing the dialysis medium every 2 hours. The critical aggregation concentration (CAC) of polylipopeptide vesicles was measured by fluorescence method using pyrene as fluorescent probe. The concentrations of cRGD-CLP and CLP ranged from 1.2 × 10 -5 to 0.1 mg / mL and the concentration of pyrene in each sample was 0.6 μM. Fluorescence intensity at 372 nm and 383 nm was recorded by a fluorescence spectrophotometer under excitation at 330 nm. The inflecti...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
encapsulation rateaaaaaaaaaa
Login to view more

Abstract

The invention discloses a polyester peptide vesicle with the inner membrane with negative charges and a preparation method and application of the polyester peptide vesicle, and belongs to the technical fields of high molecular materials and practical chemistry. The preparation method comprises the steps that a PEG-b-PAPA-b-PAsp tri-block polymer is simply prepared through NCA ring opening polymerization and deprotection, wherein cRGD-CLP obtained through preparation has the advantages of being small in size, good in stability and high in protein encapsulation amount; the cRGD-CLP (SAP-cRGD-CLP) with soapwart toxin proteins can be specifically targeted to alphavbeta3 integrin overe-xpressed tumor cells, and shows high cytotoxicity to A549 lung cancer cells. The cRGD-CLP can be long circulated in vivo, enrichment of a protein drug at the tumor site is further promoted, and in-situ A549 lung cancer growth is completely inhibited. Therefore, the vesicle is easily prepared, the protein loading capacity is high, the tumor targeting ability is high, and the polyester peptide vesicle has a great potential in protein treatment of tumors.

Description

technical field [0001] The invention relates to a polylipopeptide vesicle whose inner membrane is negatively charged, a preparation method and application thereof, and belongs to the technical field of polymer materials and applied chemistry. Background technique [0002] Protein drugs have shown unique advantages in cancer treatment. Compared with traditional small-molecule chemotherapy drugs, therapeutic protein drugs such as monoclonal antibodies, enzymes, and hormones have the characteristics of strong specificity and high activity. However, their inherent structural instability, easy degradation and inactivation during in vivo circulation, poor cell penetration and immunogenicity have greatly hindered the clinical transformation of protein drugs. Therefore, how to safely and efficiently deliver therapeutic proteins that need to function in cells to cancer cells is a major challenge in the field of protein therapy. Polymeric vesicles have a huge hydrophilic inner cavit...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C08G69/40C08G69/08A61K9/127A61K47/34A61P35/00
CPCA61K47/34A61P35/00A61K9/1273C08G69/08C08G69/40
Inventor 邓超邱敏钟志远
Owner SUZHOU UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap