Preparation And Properties Of Poly (N,N-dimethylaminoethyl Methacrylate) Nanogels Based On In-situ Template Polymerization

Nanogels are of great significance in the biomedical field,because their good water dispersibility,mechanical stability,high hydrophilic drug loading capacity and specific environmental responsiveness.Cationic poly(dimethylaminoethyl methacrylate)(PDMAEMA)nanogels are widely used for drug,gene and protein delivery due to their pH,temperature,ionic strength multi-responsiveness.However,PDMAEMA nanogels still face enormous challenges in morphology control,batch repeat preparation,blood circulation stability and cytotoxicity.Therefore,it is important to develop new methods to prepare PDMAEMA-based nanogels with uniform size,high circulation stability,good biocompatibility and responsive drug release behavior.In this paper,the following studies were conducted based on the preparation,stability,toxicity and responsive drug release of PDMAEMA nanogels.(1)Liposome-coated pH-sensitive PDMAEMA nanogels(PDMAEMA@liposome NGs)were prepared by in-situ template polymerization using PEGylated liposomes as templates,and the drug loaded liposome-coated PDMAEMA nanogels were prepared by ultrasonic hydration.Then the effect of PEGylated liposomes on the morphology,stability,pH responsiveness,cellular uptake and cytotoxicity of PDMAEMA nanogels was investigated.The results showed that the size of PDMAEMA@liposome NGs was uniform and controllable,which can be controlled by adjusting the size of liposome templates.The PEGylated liposomes on the surface of PDMAEMA nanogels improved the storage stability,anti-protein adsorption stability and hemocompatibility of PDMAEMA nanogels.In addition,PDMAEMA@liposome NGs could prevent drug leakage at pH 7.4,and released drug rapidly at pH 5.0.Furthermore,the results indicated that DOX?HCl-loaded PDMAEMA@liposome NGs had comparable cytotoxicity to the free DOX?HCl to HepG-2 cells.(2)Liposome coated multi-responsive PDMAEMA nanogels(MR-lipogels)were prepared by in-situ template polymerization,which using PEGylated liposomes as templates,pH and temperature dual-responsive 2-(dimethylamino)ethyl methacrylate(DMAEMA)as a monomer,hydrophilic redox-cleavable cystine methacrylate(CDA)as a crosslinking agent.The results showed that the size increased as the pH or temperature decreased.The structure of MR-lipogels was uniform sphere,which could be destroyed when treated with glutathione(GSH),thus MR-lipogels can realize redox responsive disintegration.The drug release showed that the MR-lipogels were multi-responsive to pH,redox and temperature.