Preparation strategies of thermo-sensitive P(NIPAM-co-AA) microspheres with narrow size distribution

Preparation strategies of thermo-sensitive P(NIPAM-co-AA) microspheres with narrow size distribution
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窄粒径分布热敏P(NIPAM-co-AA)微球的制备策略

DOI:
10.1016/j.powtec.2012.04.060
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发表时间:
2013-02
期刊:
影响因子:
5.2
通讯作者:
Ma, Guanghui
Ma, Guanghui
中科院分区:
工程技术2区
文献类型:
--
作者:
Qin, Jia;Wei, Yi;Li, Chunping;Ma, Guanghui

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刺激响应型聚合物微球在药物传递系统中的应用越来越受到人们的关注,因为它具有广泛的封装和触发释放功能。本文采用预混膜乳化技术与低温聚合相结合的新工艺,成功制备了尺寸分布较窄的热敏性聚(n -异丙基丙烯酰胺-共丙烯酸)[P(NIPAM-co-AA)]微球。将粒径分布较宽的油包水粗乳液在氮气压力下多次压过白苏多孔玻璃(SPG)膜,形成粒径分布较窄的细乳液。为了避免热敏性P(NIPAM-co-AA)微球在聚合过程中发生相变引发的聚集,将N, N, N′N′-四亚甲基二胺(TEMED)加入到W/O乳液中,在低温下引发聚合。采用共聚焦激光扫描显微镜(CLSM)和zeta电位分析仪对其形貌和尺寸分布进行了研究。从几种染料中筛选出罗丹明123标记P(NIPAM-co-AA)微球,并用CLSM对其进行表征。研究了聚合过程中跨膜压力、跨膜次数和搅拌速率对微球粒径分布的影响。优化后的制备条件为:孔径为5.2μm的膜,跨膜压力为250kPa,跨膜次数为3次。所得微球在5.11左右,多分散性指数为0.0312。膜孔径(X)与微球平均直径(Y)呈良好的线性关系(Y=0.89X+0.62, R2=0.999)。该研究也为制备其他尺寸分布窄的热敏微球提供了思路,在给药系统(DDS)中具有广泛的应用前景。
Stimuli-responsive polymer microspheres have attracted great attention due to their applications in drug delivery system which can offer considerable versatility for encapsulation and triggered release. In this article, thermo-sensitive poly (N-isopropyl acrylamide-co-acrylic acid) [P(NIPAM-co-AA)] microspheres with narrow size distribution were successfully prepared using a new technique-premix membrane emulsification technique combined with low temperature polymerization. Coarse W/O (water in oil) emulsion with broad size distribution was repeatedly pressed through Shirasu Porous Glass (SPG) membrane under nitrogen gas pressure to form the fine emulsion with narrow size distribution. In order to avoid phase transition triggered aggregation of thermo-sensitive P(NIPAM-co-AA) microspheres during polymerization, N, N, N′ N′-tetramethylethylene-diamine (TEMED) was introduced to polymerization system by adding it into W/O emulsion to initiate polymerization at low temperature. The morphology and size distribution were investigated by confocal laser scanning microscopy (CLSM) and zeta potential analyzer. Rhodamine 123 was screened out from several dyes to label P(NIPAM-co-AA) microspheres in order to characterize them by CLSM. Effects of trans-membrane pressure, number of cross membrane passes and stirring rate during polymerization on size distribution of the microspheres were investigated in detail. The optimized preparation conditions were determined as follows: trans-membrane pressure was 250kPa and trans-membrane passes were three times when using a membrane of 5.2μm pore size. The obtained microspheres were around 5.11 with the polydispersity index of 0.0312. Good linear relationship (Y=0.89X+0.62, R2=0.999) between the membrane pore size (X) and the mean diameter of the microspheres (Y) was observed. This research would also shed light on preparation of other thermo-sensitive microspheres with narrow size distribution, which would have extensive applications in drug delivery system (DDS).
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