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合成及表征一种无细胞毒性、生物相容性的丙烯酰胺接枝普鲁兰多糖-在 pH 响应性控制药物释放中的应用。

Synthesis and characterization of a non-cytotoxic and biocompatible acrylamide grafted pullulan - Application in pH responsive controlled drug delivery.

机构信息

Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India.

Biomaterial and Tissue Engineering Laboratory, Department of Biosciences & Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781 039, Assam, India.

出版信息

Int J Biol Macromol. 2018 Dec;120(Pt A):753-762. doi: 10.1016/j.ijbiomac.2018.08.123. Epub 2018 Aug 25.

Abstract

The aim of present study was to develop a pH responsive rate controlling polymer by acrylamide grafting onto pullulan. Grafting was performed using free radical induced microwave assisted irradiation technique using ceric ammonium nitrate as free radical inducer. Acrylamide grafted pullulan (Aam-g-pull) was characterized by Fourier transform infrared spectroscopy, solid state C nuclear magnetic resonance and field emission scanning electron microscopy. In vitro enzymatic degradation of Aam-g-pull showed degradation of 22.45% after 8 h with degradation rate constant (k) of 0.019 min. In vitro cytotoxicity test did not show cell viability below 80% on HepG2 cell line. Pirfenidone tablets were prepared by utilizing wet granulation method using Aam-g-pull as the only rate controlling polymer. The tablets were characterized in terms of in-process quality control parameters like weight variation, hardness, assay, and in vitro dissolution study. The dissolution study showed that the cumulative drug release in phosphate buffer pH 6.8 (rel = 44.12 ± 0.56%) got a significant jump as compared to the release in 0.1 N hydrochloric acid (rel = 26.78 ± 0.23%), confirming the material to be pH responsive. Aam-g-pull can be used as pH responsive rate controlling polymer.

摘要

本研究旨在通过丙烯酰胺接枝到普鲁兰上开发一种 pH 响应型控释聚合物。接枝是在硝酸铈铵作为自由基引发剂的自由基诱导微波辅助辐照技术下进行的。用傅里叶变换红外光谱、固态 C 核磁共振和场发射扫描电子显微镜对丙烯酰胺接枝普鲁兰(Aam-g-pull)进行了表征。Aam-g-pull 的体外酶降解在 8 小时后显示降解了 22.45%,降解速率常数(k)为 0.019 min。体外细胞毒性试验在 HepG2 细胞系上未显示细胞活力低于 80%。利用 Aam-g-pull 作为唯一的控释聚合物,采用湿法制粒法制备了吡非尼酮片。对片剂进行了过程质量控制参数的表征,如重量变化、硬度、含量测定和体外溶出度研究。溶出度研究表明,与在 0.1 N 盐酸中的释放(rel = 26.78 ± 0.23%)相比,在磷酸盐缓冲液 pH 6.8 中的累积药物释放(rel = 44.12 ± 0.56%)有显著提高,证实该材料具有 pH 响应性。Aam-g-pull 可用作 pH 响应型控释聚合物。

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