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基于喷墨打印的热响应性核壳聚合物微胶囊组装用于药物控释

Inkjet printing based assembly of thermoresponsive core-shell polymer microcapsules for controlled drug release.

作者信息

Yang Jianmin, Katagiri Daisuke, Mao Sifeng, Zeng Hulie, Nakajima Hizuru, Kato Shungo, Uchiyama Katsumi

机构信息

Department of Applied Chemistry, Graduate School of Urban Environmental Sciences, Tokyo Metropolitan University, Minamiohsawa, Hachioji, Tokyo 192-0397, Japan.

出版信息

J Mater Chem B. 2016 Jun 21;4(23):4156-4163. doi: 10.1039/c6tb00424e. Epub 2016 May 23.

Abstract

A controlled drug delivery system (DDS) was designed by integrating the thermoresponsive copolymer poly(N-isopropylacrylamide-co-methacrylic acid) (poly(NIPAAm-co-MAA)) with core-shell 1,6-hexanediol diacrylate (HDDA) microparticles. The monodisperse HDDA particles with a hollow core and a nanoporous shell were fabricated in a continuous manner by an initially proposed inkjet printing process combined with UV polymerization. The thermoresponsive poly(NIPAAm-co-MAA) copolymer was grafted onto the surface of HDDA microcapsules by free radical initiated polymerization. Particularly, the lower critical solution temperature (LCST) of the copolymer was adjusted to human physiological temperature by the optimal comonomer ratio of MAA. With temperature changes at around the LCST, the copolymer, which was modified on the internal nanopore, served as a "retractable gate" by virtue of its changes in conformation between swollen and collapsed structures. Thus, controlled drug release was achieved by the reversible "open-close" transition characteristics of the nanopores. Fluorescein as a hypothetical drug molecule was loaded in the microcapsules and used to investigate the controlled release of the material. The results confirmed that this system represents a promising candidate for use in preparing controlled DDSs.

摘要

通过将热响应性共聚物聚(N-异丙基丙烯酰胺-co-甲基丙烯酸)(聚(NIPAAm-co-MAA))与核壳型1,6-己二醇二丙烯酸酯(HDDA)微粒相结合,设计了一种可控药物递送系统(DDS)。通过最初提出的结合紫外光聚合的喷墨印刷工艺,以连续方式制备了具有中空核和纳米多孔壳的单分散HDDA颗粒。通过自由基引发聚合将热响应性聚(NIPAAm-co-MAA)共聚物接枝到HDDA微胶囊的表面。特别地,通过MAA的最佳共聚单体比例将共聚物的低临界溶液温度(LCST)调节至人体生理温度。随着温度在LCST附近变化,在内部纳米孔上修饰的共聚物由于其在溶胀和塌陷结构之间构象的变化而充当“可伸缩门”。因此,通过纳米孔的可逆“开闭”转变特性实现了药物的可控释放。将荧光素作为假设的药物分子负载在微胶囊中,并用于研究该材料的可控释放。结果证实,该系统是制备可控DDS的有前途的候选者。

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