微乳液法制备可共载水溶和脂溶药物的壳聚糖季铵盐乙醇脂质体的载药性能表征

摘要

采用微乳液法制备了可包载脂溶性和水溶性药物的羧甲基壳聚糖十八烷基季铵盐(OQCMC)乙醇脂质体,研究了OQCMC乙醇高分子脂质体的相图、粒径和电位、对药物的包封及释放能力及共载水溶性和脂溶性荧光染料后的细胞内递送能力.结果表明:OQCMC上长链季铵盐分子的取代度和共乳化剂乙醇的加入量对相图中微乳区域的面积影响不大;微乳液法町制备包载水溶性长春新碱(VCR)、脂溶性消炎痛(IMC)或二者共载的OQCMC载药微球,微球粒径为(52.40+0.55) nm,分布均匀;微乳液体系对VCR的最大载药率为22.7％,对IMC的最大载药率为20.1％,二者共载时,VCR的最大载药率为12.2％,IMC的最大载药率为10.0％;载药微球对药物具有缓控释功能.OQCMC乙醇高聚物脂质体可有效地包载荧光染料异硫氰酸荧光素FITC(水溶性)和尼罗红(脂溶性),并将二者递送到卵巢癌H08901细胞内.%Polymeric ethosomes,formed from amphiphilic octadecyl quaternized carboxymethyl chitosan (OQCMC) with different degrees of quaternary substitution (DS),were prepared by the microemulsion (ME) method.These ethosomes could simultaneously encapsulate both the hydrophobic drug indomethacin (IMC) and the hydrophilic drug vincristine (VCR).The effects of the DS of the OQCMC and primary alcohols as cosurfactants on the phase diagram were elucidated.The prepared nanoparticles (NPs) were small ((52.40± 0.55) nm) and suitable as drug carriers for different drugs.The maximum drug loading efficiencies of VCR-loaded and IMC-Ioaded NPs were 22.7％ and 20.1％,respectively.The drug loading capacities for co-delivery of VCR and IMC were 12.2％ and 10.0％,respectively.OQCMC polymeric ethosomes were stable in aqueous solution and exhibited slow,steady drug release.Hydrophilic fluorescein isothiocyanate (FITC) and hydrophobic Nile Red were encapsulated by the OQCMC ME NPs and simultaneously delivered into HO8901 cells with green and red fluorescence,respectively.This co-delivery system may allow for temporally distinct classes of drugs for cancer therapy.