Department of Pharmaceutical, Chemical & Environmental Sciences, School of Science, University of Greenwich at Medway, Chatham Maritime, Kent, UK.
Colloids Surf B Biointerfaces. 2012 Feb 1;90:102-8. doi: 10.1016/j.colsurfb.2011.10.005. Epub 2011 Oct 12.
The objective of this study was to develop pH sensitive polymethacrylic acid-chitosan-polyethylene glycol (PCP) nanoparticles. This was achieved by dispersion polymerization of methacrylic acid (MAA), polyethylene glycol (PEG) and different chitosan (CS) grades in the presence of cross linking agent ethylene dimethacrylate (EDMA) and polymer initiator potassium persulphate. Method development was carried out by varying formulation parameters such as type of CS, ratio of PEG to CS, quantity of solvent and polymer initiator. Metoprolol (MTP) tartrate was incorporated into the nanoparticles (NPs) as a model drug. Laser diffraction, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies revealed that the NPs were spherical with smooth surfaces ranging in size from 190 to 450 nm. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) findings showed the presence of amorphous MTP in PCP NPs. The MTP loading of PCP and glycol chitosan (GC) NPs varied from 10 to 45% depending on the CS grade while both types of NPs showed excellent binding efficiency on mucin from porcine stomach. The in vitro dissolution study showed pH dependent release profiles suggesting that the PCP NPs system have great potential for oral controlled drug delivery as an alternative to conventional dosage forms.
本研究旨在开发 pH 敏感的聚甲基丙烯酸-chitosan-聚乙二醇（PCP）纳米粒子。这是通过在交联剂二甲基丙烯酸乙二醇酯（EDMA）和聚合物引发剂过硫酸钾存在下，将甲基丙烯酸（MAA）、聚乙二醇（PEG）和不同壳聚糖（CS）级分分散聚合来实现的。方法开发通过改变配方参数来进行，例如 CS 的类型、PEG 与 CS 的比例、溶剂和聚合物引发剂的用量。酒石酸美托洛尔（MTP）被掺入纳米粒子（NPs）中作为模型药物。激光衍射、扫描电子显微镜（SEM）和透射电子显微镜（TEM）研究表明， NPs 呈球形，表面光滑，粒径为 190 至 450nm 不等。X 射线衍射（XRD）和差示扫描量热法（DSC）的结果表明，PCP NPs 中存在无定形的 MTP。PCP 和乙二醇壳聚糖（GC）NPs 的 MTP 负载量根据 CS 级分的不同而在 10%至 45%之间变化，而这两种类型的 NPs 均对猪胃粘蛋白表现出优异的结合效率。体外溶解研究表明，释放曲线具有 pH 依赖性，这表明 PCP NPs 系统具有作为传统剂型替代物进行口服控释药物递送的巨大潜力。
