离子型温敏纳米凝胶的制备及其载药性能评价  

Preparation of thermosensitive ionic nanogels and evaluation of their drug loading capacity

作　　者：熊微[1] 施春阳[1] 王文清[1] 方建国[1] 赵彦兵[2] 杨祥良[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院药学部,湖北武汉430030 [2]华中科技大学生命科学与技术学院,湖北武汉430074

出　　处：《中国医院药学杂志》2015年第10期897-902,共6页Chinese Journal of Hospital Pharmacy

基　　金：湖北省自然科学基金项目(编号:2011CDB210)

摘　　要：目的：制备离子型N-异丙基丙烯酰胺（NIPAM）类温敏纳米凝胶用于静电吸附载药。方法：分别采用乳液聚合（EP）、种子乳液聚合（SEP）和无皂乳液聚合（SFEP）法将NIPAM与丙烯酸（AA）或甲基丙烯酸β-硫酸乙基酯（SEMA）共聚制成纳米凝胶,通过TEM、PCS、电位滴定等方法表征各凝胶颗粒的形貌尺寸、温敏行为及单体含量。以阿霉素为模型药物,考察纳米凝胶通过静电吸附载药的能力。结果：EP或SEP法制备的AA凝胶（PNA）单分散性和温敏性良好,单体能完全参与聚合,当温度从20℃升至45℃时,粒径约从100 nm降至50 nm。EP法制备的SEMA凝胶（PNS）单分散性较差,改用SFEP法能提高凝胶的单分散性,但是约40%单体没有参与共聚。PNS凝胶的温敏性仍得到保留,20~45℃下粒径约为200~140 nm。核-壳型纳米凝胶的载药量和包封率最低,随着交联密度的增大,PNA纳米凝胶的载药量也相应提高。PNS纳米凝胶的载药量和包封率分别为14.6%和85.3%,载药能力最强,约为PNA纳米凝胶的2~3倍。PNS纳米凝胶负载的药物在纯水中24 h不释放,在生理盐水中约2 h释放完全。结论：PNS纳米凝胶粒径均一,具有温敏性,载药性能好,有望成为一个智能响应性纳米药物载体。OBJECTIVE To prepare N-isopropylacrylamide （NIPAM） based thermosensitive ionic nanogels for drug loading by electrostatic adsorption. METHODS The emulsion polymerization （EP）, seed emulsion polymerization （SEP） and soap- free emulsion polymerization （SFEP） were used to prepare nanogels by copolymerization of NIPAM with acrylic acid （AAe） or β-sulfatoethyl methacrylate （SEMA）. The morphology, size, temperature-sensitivity and co-monomer content of obtained nanogels were characterized by TEM, PCS and potentiometrie titration. Their drug loading capacity by electrostatic adsorption was also evaluated using doxoruhicin as a model drug. RESULTS AAc nanogels （PNA） prepared by EP or SEP which the co- monomers could fully participate in polymerization, had a high monodispersity and temperature-sensitivity that was about 100- 50 nm of particles size in the range of 20 - 45 ℃. Compared with low monodispersity of SEMA nanogels （PNS） prepared by EP, PNS nanogeis synthesized by SFEP had a better monodispersity and retained the temperature-sensitivity that was about 200 - 140 nm of particles size in the same temperature range. Meanwhile, about 40% of co-monomer was not copolymerized in to PNS nanogels. The drug-loading and encapsulation efficiencies were lowest for core-shell nanogels, and increased with the nanogels cross-linking density. PNS nanogels had highest drug loading capacity, and the drug loading rate and encapsulation ef- ficiency were 14. 6% and 85. 3%, respectively, about 2 to 3 times higher than PNA nanogels. The loaded-drug was not re- leased in water in 24 h, but was completely released in have uniform particle size, high drug loading capacity, sive drug carriers. physiological saline solution in 2 h. CONCLUSION PNS nanogels which and temperature sensitivity, are expected to become intelligent respon-sive drug carriers.

关 键 词：纳米凝胶 无皂乳液聚合 药物载体 温敏性 静电吸附 

分 类 号：R943[医药卫生—药剂学]