Cheaburu-Yilmaz Catalina Natalia, Yilmaz Onur, Kose Fadime Aydin, Bibire Nela
Department of Physical Chemistry of Polymer "Petru Poni" Institute of Macromolecular Chemistry, 700487 Iaşi, Romania.
Ege University, Faculty of Engineering, Leather Engineering Department, 35100 Bornova-Izmir, Turkey.
Polymers (Basel). 2019 Aug 31;11(9):1432. doi: 10.3390/polym11091432.
The objective of this study was to prepare and characterize physically crosslinked gel formulations of chitosan (CS)-graft-poly(N-isopropyl acrylamide) (PNIPAAm) and polyvinyl alcohol (PVA) for smart delivery of an antifungal drug, Voriconazole, for mucosal applications. For this purpose, cryogels of CS--PNIPAAm/PVA and CS/PVA were tested by means of texture profile analysis and rheology to determine optimal matrix properties for topical application. The ratio of 75/25 / % CS--PNIPAAm/PVA was selected to be used for formulation since it gave low compressibility and hardness (1.2 and 0.6 N) as well as high adhesion properties and non-Newtonian flow behavior. The cryogels and formulations were further characterized by means of FTIR spectroscopy, swelling behavior, texture analysis, scanning electron microscopy (SEM), thermal (differential scanning calorimetry (DSC) and TGA), and rheological behavior. The drug loading capacity and in vitro release profile of the drug, storage stability, and cytotoxicity tests were also performed for the gel formulation. The FTIR, DSC, and TGA results verified the successful formation of cryogels. Swelling studies revealed a pH-dependent swelling ability with a maximum swelling degree of 1200% in acid and 990% in phosphate buffer (pH 7.4). Thermal studies showed that CS--PNIPAAm/PVA 75/25 had higher thermal stability proving the structural complexity of the polymer. The loading capacity of Voriconazole was found to be 70% (/). The in vitro release profiles of Voriconazole showed Fickian release behavior for CS--PNIPAAm/PVA 75/25 gel with an approximate delivery of 38% within 8 h, slower than matrices containing unmodified chitosan. The storage stability test exhibited that the gel formulation was still stable even after aging for two months. Moreover, the cell culture assays revealed a non-toxic character of the polymeric matrix. Overall results showed that the CS--PNIPAAm/PVA 75/25 hydrogel has the potential to be used as a smart polymeric vehicle for topical applications.
本研究的目的是制备并表征壳聚糖（CS）接枝聚（N-异丙基丙烯酰胺）（PNIPAAm）和聚乙烯醇（PVA）的物理交联凝胶制剂，用于抗真菌药物伏立康唑的智能递送，以用于黏膜应用。为此，通过质地剖面分析和流变学对CS-PNIPAAm/PVA和CS/PVA的冷冻凝胶进行测试，以确定局部应用的最佳基质特性。选择75/25/% CS-PNIPAAm/PVA的比例用于制剂，因为它具有低压缩性和硬度（1.2和0.6 N）以及高粘附性和非牛顿流动行为。通过傅里叶变换红外光谱（FTIR）、溶胀行为、质地分析、扫描电子显微镜（SEM）、热分析（差示扫描量热法（DSC）和热重分析（TGA））以及流变行为对冷冻凝胶和制剂进行进一步表征。还对凝胶制剂进行了药物负载能力、药物的体外释放曲线、储存稳定性和细胞毒性测试。FTIR、DSC和TGA结果证实了冷冻凝胶的成功形成。溶胀研究表明，其溶胀能力依赖于pH值，在酸性条件下最大溶胀度为1200%，在磷酸盐缓冲液（pH 7.4）中为990%。热分析表明，CS-PNIPAAm/PVA 75/25具有更高的热稳定性，证明了聚合物的结构复杂性。伏立康唑的负载能力为70%（/）。伏立康唑的体外释放曲线显示，CS-PNIPAAm/PVA 75/25凝胶具有菲克扩散释放行为，在8小时内约释放38%，比含有未改性壳聚糖的基质释放速度慢。储存稳定性测试表明，即使老化两个月后，凝胶制剂仍然稳定。此外，细胞培养试验表明聚合物基质具有无毒性。总体结果表明，CS-PNIPAAm/PVA 75/25水凝胶有潜力用作局部应用的智能聚合物载体。
