Study On Polyethylene Glycol-polylactic Acid-polyethylene Glycol Triblock Copolymer Polymersome Drug Delivery System

Nowadays,with the development of medicine,degradable polymer has been widely used in biomedical materials,and its good biocompatibility and degradability have become the focus of most researchers.Copolymers of polylactic acid(PLA)and polyethylene glycol(PEG)have been used in the biomedical field,including surgical sutures,cardiac occlusion devices,drug delivery vehicles,and tissue engineering scaffolds.In recent years,polymersomes prepared from amphiphilic triblock copolymers have been extensively studied as drug carriers.At the same time,the vesicle has high permeability and retention effect(EPR effect),which can achieve high concentration accumulation in the tumor site,and can also meet the requirements of long circulation in the body.The polymersomes have a hydrophilic-hydrophobic-hydrophilic three-layer structure,and thus can simultaneously contain both pro-and hydrophobic drugs with different water solubility.Therefore,it is important to study the amphiphilic triblock copolymer polymersomes for sustained release of drugs.In this paper,polyethylene glycol was used as initiator to obtain PEG-PLA diblock copolymers by ring-opening polymerization of lactide under the catalysis of stannous octoate.The terminal alkyne was reacted with azide PEG to form triblock copolymer PEG-PLA-PEG.The composition,structure,molecular weight and thermodynamic properties of the triblock copolymer were investigated by ~1H NMR and GPC methods.The polymersomes were prepared by a solvent evaporation method,and the morphology and size of the polymersomes were observed by means of TEM,DLS,or the like.This topic selects two different water-soluble drugs,hydrophobic paclitaxel and hydrophilic cisplatin,which are loaded by dialysis,the drug loading and encapsulation efficiency of polymersomes and drug release by high performance liquid chromatography(HPLC).And inductively coupled plasma spectroscopy(ICP)testing.To test the toxicity of triblock copolymer materials,blood compatibility,cytocompatibility and zebrafish embryo toxicity experiments were performed to evaluate their biocompatibility.The PEG-PLA-PEG triblock copolymerspolymersomes were tested in vitro to simulate degradation in vivo,and their degradation behaviors were studied by TEM,DLS and GPC.The results showed that the self-assembly of PEG-PLA-PEG triblock copolymers into polymersomes was successfully achieved by cosolvent evaporation method.The drug-loading performance was better,with higher encapsulation efficiency and drug loading.Drug release tends to smooth.The polymersomes formed by self-assembly of PEG-PLA-PEG triblock copolymers have good biocompatibility,whether it is cell,blood compatibility evaluation or zebrafish embryo toxicity test,indicating the self-assembled capsule.Bubble is an ideal clinical drug sustained release system.At the same time,the drug loading and encapsulation efficiency of the two drugs in the polymersomes drug-loading system were relatively high,and the release curve of the drug in one week was relatively stable,and there was no obvious burst release phenomenon.In addition,when the length of the hydrophobic block is short,the release rate of the hydrophobic drug is faster.The degradation experiments showed that the triblock copolymer polymersomes degraded completely at 45 days.The degradation time of the hydrophobic segment of the PLA depends on the length of the segment.If the proportion of the PLA segment is higher,the degradation time is prolonged and the structural disintegration tends to be slow.