Fathalla Zeinab, Fatease Adel Al, Abdelkader Hamdy
Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62223, Saudi Arabia.
Polymers (Basel). 2023 Jun 21;15(13):2773. doi: 10.3390/polym15132773.
Innovative hybrid chitosan-sodium alginate (Ch-Ag) microparticles (MPs) were fabricated using both the ionic gelation method as well as the pre-gelation technique. The hybrid Ch-Ag MPs were studied for size, zeta potential, morphology, mucoadhesion, in-vitro release, corneal permeation, and ocular irritation using lens and corneal epithelial cell lines. The average particle size ranged from 1322 nm to 396 nm. The zeta potential for the prepared formulations showed an increase with increasing Ch concentrations up to a value of >35 mV; the polydispersity index (PDI) of some optimized MPs was around 0.1. Compared to drug-free MPs, ketorolac-loaded Ch-Ag MPs demonstrated a drug proportion-dependent increase in their size. SEM, as well as TEM of KT-loaded MPs, confirmed that the formed particles were quasi-spherical to elliptical in shape. The KT release from the MPs demonstrated a prolonged release profile in comparison to the control KT solution. Further, mucoadhesion studies with porcine mucin revealed that the KT-loaded MPs had effective mucoadhesive properties, and polymeric particles were stable in the presence of mucin. Corneal permeation was studied on bovine eyes, and the results revealed that Ch-based MPs were capable of showing more sustained KT release across the cornea compared with that for the control drug solution. Conclusively, the cytotoxicity assay confirmed that the investigated MPs were non-irritant and could confer protection from direct drug irritation of KT on the ocular surface. The MTT cytotoxicity assay confirmed that KT-loaded MPs showed acceptable and reasonable tolerability with both human lens and corneal epithelial cell lines compared to the control samples.
采用离子凝胶法和预凝胶技术制备了创新性的壳聚糖-海藻酸钠（Ch-Ag）混合微粒（MPs）。使用晶状体和角膜上皮细胞系对混合Ch-Ag MPs进行了粒径、zeta电位、形态、粘膜粘附性、体外释放、角膜渗透和眼刺激性研究。平均粒径范围为1322 nm至396 nm。所制备制剂的zeta电位随Ch浓度增加而升高，直至>35 mV；一些优化后的MPs的多分散指数（PDI）约为0.1。与不含药物的MPs相比，载酮咯酸的Ch-Ag MPs的粒径随药物比例增加而增大。载酮咯酸MPs的扫描电子显微镜（SEM）和透射电子显微镜（TEM）证实，形成的颗粒形状为准球形至椭圆形。与对照酮咯酸溶液相比，MPs中酮咯酸的释放呈现出延长的释放曲线。此外，与猪粘蛋白的粘膜粘附性研究表明，载酮咯酸的MPs具有有效的粘膜粘附特性，并且聚合物颗粒在粘蛋白存在下是稳定的。在牛眼上进行了角膜渗透研究，结果表明，与对照药物溶液相比，基于Ch的MPs能够在角膜上更持续地释放酮咯酸。总之，细胞毒性试验证实，所研究的MPs无刺激性，并且可以防止酮咯酸对眼表的直接药物刺激。MTT细胞毒性试验证实，与对照样品相比，载酮咯酸的MPs对人晶状体和角膜上皮细胞系均表现出可接受且合理的耐受性。
