Fang Jia-You, Chen Jyh-Ping, Leu Yann-Lii, Hu Jiuan-Wen
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Drug Deliv. 2008 May;15(4):235-43. doi: 10.1080/10717540802006674.
New thermosensitive hydrogels of poly(N-isopropylacrylamide) (PNIPAAm) with chitosan (CPN) were prepared and evaluated for use in the delivery of the platinum drugs, cisplatin and carboplatin. The effects of polymers containing different ratios of chitosan on the physicochemical and drug release characteristics were examined. The sol-gel transition temperature of the hydrogels was determined by differential scanning calorimetry (DSC) and viscometry. Discrepancies in the transition temperature among the various polymer systems were more pronounced when determined by viscosity compared by DSC, with the CPN showing a higher transition temperature than PNIPAAm. The cross-sectional structure and surface topography of the hydrogels were examined by scanning electronic microscopy (SEM) and atomic force microscopy (AFM), respectively. The incorporation of chitosan further increased the entanglement of the hydrogel network. An increase in the chitosan ratio in the polymers (CPN-H) also increased the cross-linking structure. A smoother surface of hydrogel matrices was observed for CPN compared with PNIPAAm. All hydrogels tested significantly reduced drug release compared with an aqueous solution. The release rate of platinum drugs from PNIPAAm was retarded at the late stage. CPN matrices could continuously deliver platinum drugs during the experiment. The rate of release from CPN-H was generally slower than that from hydrogels and had a lower chitosan ratio (CPN-L), presumably due to the more-tortuous pathways in the hydrogels. Thermosensitive hydrogels like those prepared in this study may be a promising carrier for the delivery of platinum drugs, as the drug release can be controlled and sustained using CPN networks.
制备了聚(N-异丙基丙烯酰胺)(PNIPAAm)与壳聚糖(CPN)的新型热敏水凝胶,并对其用于铂类药物顺铂和卡铂的递送进行了评估。研究了壳聚糖不同比例的聚合物对其物理化学和药物释放特性的影响。通过差示扫描量热法(DSC)和粘度测定法确定水凝胶的溶胶-凝胶转变温度。与DSC相比,通过粘度测定时,各种聚合物体系之间的转变温度差异更为明显,CPN的转变温度高于PNIPAAm。分别通过扫描电子显微镜(SEM)和原子力显微镜(AFM)检查水凝胶的横截面结构和表面形貌。壳聚糖的加入进一步增加了水凝胶网络的缠结。聚合物(CPN-H)中壳聚糖比例的增加也增加了交联结构。与PNIPAAm相比,CPN的水凝胶基质表面更光滑。与水溶液相比,所有测试的水凝胶均显著降低了药物释放。PNIPAAm中铂类药物的释放速率在后期受到抑制。CPN基质在实验过程中可以持续递送铂类药物。CPN-H的释放速率通常比壳聚糖比例较低的水凝胶(CPN-L)慢,这可能是由于水凝胶中路径更曲折。本研究中制备的热敏水凝胶可能是一种有前途的铂类药物递送载体,因为可以使用CPN网络控制和持续药物释放。