Chearúil Fiona Ní, Corrigan Owen I
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland.
Int J Pharm. 2009 Jan 21;366(1-2):21-30. doi: 10.1016/j.ijpharm.2008.08.036. Epub 2008 Sep 3.
A series of thermoresponsive-co-biodegradable polymers, containing varying molar ratios of N-isopropylacrylamide (NIPA) and poly-lactic acid diacrylate macromer (PLAM) were prepared and characterised. Chemical structures were confirmed by nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR). The hydrogels were thermoresponsive, exhibiting an increase in the lower critical solution temperature (LCST) the higher the percent of PLAM present. Swelling properties were dependant on both temperature and PLAM content. The degradation behaviour of the three-dimensional polymeric networks formed was dependent on both structural (mesh size, molecular weight distribution, composition) and environmental parameters (temperature). Swelling and in vitro biodegradation-induced morphological structural changes were examined using scanning electron microscopy (SEM). A greater rate of degradation and disruption to the porous network could be seen with increasing lactide content. Degradation was faster below the LCST, demonstrated by FTIR, pH decrease and acid release, consistent with the increased hydrophilicity of the network. The release profiles of the model drug indomethacin (IDM), from these thermoresponsive-co-biodegradable polymers, were found to be dependant on copolymer composition, drug loading and temperature, more rapid release occurring below the LCST.
制备并表征了一系列含有不同摩尔比的N-异丙基丙烯酰胺(NIPA)和聚乳酸二丙烯酸酯大分子单体(PLAM)的热响应性共生物可降解聚合物。通过核磁共振(NMR)和傅里叶变换红外光谱(FTIR)确认了化学结构。水凝胶具有热响应性,随着PLAM含量的增加,其最低临界溶液温度(LCST)升高。溶胀性能取决于温度和PLAM含量。所形成的三维聚合物网络的降解行为取决于结构参数(网孔尺寸、分子量分布、组成)和环境参数(温度)。使用扫描电子显微镜(SEM)研究了溶胀和体外生物降解引起的形态结构变化。随着丙交酯含量的增加,可以观察到降解速率加快,多孔网络受到破坏。FTIR、pH值降低和酸释放表明,在LCST以下降解更快,这与网络亲水性增加一致。发现这些热响应性共生物可降解聚合物对模型药物吲哚美辛(IDM)的释放曲线取决于共聚物组成、药物负载量和温度,在LCST以下释放更快。