温敏聚合物修饰中空介孔二氧化硅纳米粒子及其复合纳米纤维的构建与释药性能

Construction and drug release performance of thermosensitive copolymer-modified hollow mesoporous silica and the composite nanofibers

传统的载药纳米纤维存在药物负载不稳定、释放过快等问题。基于此,本文利用温敏聚合物包覆中空介孔二氧化硅纳米颗粒(HMSN),将其作为药物载体与聚己内酯(PCL)纳米纤维复合,探究了复合纳米纤维膜的释药及抗菌性能。采用自由基聚合方法在HMSN表面接枝异丙基丙烯酰胺与丙烯酰胺的共聚物(P(NIPAM-co-AM)),将疏水性药物环丙沙星(CIP)负载到共聚物改性纳米粒子(PHMSN)中,利用SEM、TEM、TG、比表面积分析(BET)、FTIR及紫外-可见吸收光谱(UV-Vis)等手段表征了HMSN和PHMSN的微观结构和温度响应性能等。将PCL与载药PHMSN共混后利用静电纺丝技术制备了复合纤维膜(CIP@PHMSN-PCL)。CIP@PHMSN-PCL具有温度刺激响应的药物控释功能,在45℃和25℃下,72 h时CIP的累计释放率分别达到90.78%和72.67%。Korsmeyer-Peppas模型较好地描述了药物释放动力学,表明扩散是复合纤维膜释药的主要机制。45℃条件下,载药纤维膜对大肠杆菌(E.coil)和金黄色葡萄球菌(S.aureus)的抑菌率均达到100%;而在25℃下,膜对两种菌的抑菌率仅为92.34%和95.83%,证明了不同温度下CIP@PHMSN-PCL膜释药性能的差异。总之,载药PHMSN复合纳米纤维膜具有环境温度调控的释药功能及优异的抗菌活性,在生物医学领域具有潜在的应用价值。

Traditional drug-loaded nanofibers face challenges such as unstable drug loading and excessively rapid release.In light of these issues,this study employs a thermosensitive copolymer(P(NIPAM-co-AM))to coat hollow mesoporous silica nanoparticles(HMSN),incorporating them as drug carriers in conjunction with poly(ε-caprolactone)(PCL)nanofibers.The drug release and antibacterial performance of the composite nanofiber membrane were investigated.Firstly,the HMSN surface was functionalized through free radical polymerization by grafting a copolymer of isopropylacrylamide(NIPAM)and acrylamide(AM)(P(NIPAM-co-AM)).Hydrophobic drug ciprofloxacin(CIP)was loaded into the modified nanoparticles(P(NIPAM-co-AM)-HMSN or PHMSN).The analysis of the microstructure,composition,and temperature-responsibility of the drug-loaded particles were performed using SEM,TEM,TG,BET analysis,FTIR,UV-Vis spectroscopy,etc.Blending PCL with drug-loaded PHMSN,a composite fibrous membrane(CIP@PHMSN-PCL)was fabricated using electrospinning.CIP@PHMSN-PCL exhibited temperature-stimulated drug releasing,with cumulative release rates of CIP reaching 90.78%and 72.67%at 45℃and 25℃after 72 h,respectively.The Korsmeyer-Peppas model apply described the drug release kinetics,suggesting the diffusion as the primary mechanisms for drug release from the composite fiber membrane.At 45℃,the drugloaded fiber membrane exhibited a 100%inhibition rate against Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus).At 25℃,the inhibition rates were 92.34%and 95.83%against E.coli and S.aureus,respectively,demonstrating temperature-dependent drug release performance of the CIP@PHMSN-PCL membrane.In summary,the drug-loaded PHMSN composite nanofiber membrane exhibits temperature-regulated drug release functionality and excellent antibacterial activity,holding potential application value in the biomedical field.