脂质体包覆的多重响应性PDMAEMA纳米凝胶的研究
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摘要
纳米载体中药物的环境响应性释放在生物医学领域具有重要意义.本文以脂质体为模板,pH和温度双响应的甲基丙烯酸二甲氨乙酯(DMAEMA)为单体,水溶性还原敏感的胱氨酸甲基丙烯酸酯(CDA)为交联剂,通过模板原位聚合法制备了脂质体包覆的pH、温度、还原多重响应性纳米凝胶(lipogels).通过透射电镜(TEM)观察lipogels形貌,采用激光粒度仪探究不同刺激条件及牛血清白蛋白(BSA)对lipogels粒径的影响.并以盐酸阿霉素为亲水性药物模型,研究不同刺激条件下lipogels的药物释放行为.结果表明,模板原位聚合法制备的lipogels呈均一的球形结构,粒径随pH值降低而增大,随温度升高而变小,在还原剂作用下lipogels结构被破坏,形貌呈碎片状.同时,lipogels具有良好的抗蛋白吸附稳定性和良好的血液相容性.体外药物释放行为表明该lipogels具有pH、还原、温度多重响应性.
The environment-responsive release behavior of drugs in nanocarriers is of great significance in biomedicine.Using liposome as a template,pH and temperature dual-responsive 2-(dimethylamino)ethyl methacrylate(DMAEMA)as a monomer,and hydrophilic redox-cleavable cystine methacrylate(CDA)as a crosslinking agent,liposome-coated pH,temperature and redox multi-responsive PDMAEMA nanogels(lipogels)were prepared by in situ template polymerization.The morphology of lipogels was observed by transmission electron microscopy(TEM).The effects of different stimulus conditions and bovine serum albumin(BSA)on the size of lipogels were measured by laser particle sizer.Using doxorubicin hydrochloride as a hydrophilic drug model,the multi-stimulated drug release behavior of lipogels was investigated.The results show that lipogels are uniform spherical structure,and their size increases as the pH or temperature decreases.Lipogels become fragmented when treated with a reducing agent.Meanwhile,lipogels have good anti-protein adsorption stability and blood compatibility.The drug release behavior indicates that lipogels are multi-responsive to pH,redox and temperature.
The environment-responsive release behavior of drugs in nanocarriers is of great significance in biomedicine.Using liposome as a template,pH and temperature dual-responsive 2-(dimethylamino)ethyl methacrylate(DMAEMA)as a monomer,and hydrophilic redox-cleavable cystine methacrylate(CDA)as a crosslinking agent,liposome-coated pH,temperature and redox multi-responsive PDMAEMA nanogels(lipogels)were prepared by in situ template polymerization.The morphology of lipogels was observed by transmission electron microscopy(TEM).The effects of different stimulus conditions and bovine serum albumin(BSA)on the size of lipogels were measured by laser particle sizer.Using doxorubicin hydrochloride as a hydrophilic drug model,the multi-stimulated drug release behavior of lipogels was investigated.The results show that lipogels are uniform spherical structure,and their size increases as the pH or temperature decreases.Lipogels become fragmented when treated with a reducing agent.Meanwhile,lipogels have good anti-protein adsorption stability and blood compatibility.The drug release behavior indicates that lipogels are multi-responsive to pH,redox and temperature.
引文
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[4]Ramos J,Forcada J,Hidalgo-Alvarez R.Cationic polymer nanoparticles and nanogels:From synthesis to biotechnological applications[J].Chemical Reviews,2014,114(1):367-428.
[5]Mandal B,Bhattacharjee H,Mittal N,et al.Coreshell-type lipid-polymer hybrid nanoparticles as a drug delivery platform[J].Nanomedicine:Nanotechnology,Biology,and Medicine,2013,9(4):474-491.
[6]Liu X,Situ A,Kang Y,et al.Irinotecan delivery by lipid-coated mesoporous silica nanoparticles shows improved efficacy and safety over liposomes for pancreatic cancer[J].ACS Nano,2016,10(2):2702-2715.
[7]Kazakov S.Liposome-nanogel structures for future pharmaceutical applications:An updated review[J].Current Pharmaceutical Design,2016,22(10):1391-1413.
[8]Zhang Y,Zhang J,Chen W,et al.Erythrocyte membrane-coated nanogel for combinatorial antivirulence and responsive antimicrobial delivery against staphylococcus aureus infection[J].Journal of Controlled Release,2017,263:185-191.
[9]Zhang J,Gao W,Fang R H,et al.Synthesis of nanogels via cell membrane-templated polymerization[J].Small,2015,11(34):4309-4313.
[10]Pikabea A,Aguirre G,Miranda J I,et al.Understanding of nanogels swelling behavior through a deep insight into their morphology[J].Journal of Polymer Science Part A:Polymer Chemistry,2015,53(17):2017-2025.
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