Kaur Harpal, Mishra Neeraj, Khurana Bharat, Kaur Sukhbir, Arora Daisy
Department of Pharmaceutics, ISF College of Pharmacy, Moga (Punjab), India.
Amity Institute of Pharmacy, Amity University of Madhya Pradesh (AUMP), Gwalior (Madhya Pradesh), India.
Curr Mol Pharmacol. 2021;14(3):381-398. doi: 10.2174/1874467213666200517120337.
The existing parenteral treatment of cervical cancer has high toxicity and poor distribution of drugs at the targeted site.
To formulate localized mucoadhesive cisplatin loaded microparticles based formulation to treat cervical cancer so that enhanced therapeutics benefits with low toxicity could be achieved.
Cisplatin loaded chitosan coated spray-dried microparticles were prepared by ionotropic gelation technique and optimized by Central Composite Design. The spray-dried uncoated and chitosan- coated microparticles were characterized for various parameters (Particle size, Morphology, Drug entrapment efficiency). In vitro drug release study was carried out in simulated vaginal fluids by dialysis membrane method. Ex vivo studies were carried out to evaluate the cytotoxic potential of the developed formulation by the MTT assay. A drug permeability study was performed by Franz diffusion cell using the vaginal tissue of Swiss Albino Mice.
All in vitro characterization parameters were found to be optimum. The in vitro release studies indicated a controlled release following the Higuchi model. The chitosan-coated microparticles were found to be more cytotoxic than uncoated microparticles and plain cisplatin solution. The chitosan-coated microparticles were found to be more permeable than uncoated microparticles. Finally, in vivo tumor regression and histopathological studies confirmed the significant decrease in tumor volume at different time intervals.
Thus, it can be concluded that mucoadhesive spray-dried microparticles could provide a favorable approach for localized delivery of the anticancer drug via vaginal route against cervical cancer with its enhanced effectiveness.
现有的宫颈癌肠胃外治疗毒性高，且药物在靶点部位的分布不佳。
制备局部黏膜黏附的载顺铂微粒制剂以治疗宫颈癌，从而实现低毒性下增强的治疗效果。
采用离子凝胶法制备壳聚糖包衣的载顺铂喷雾干燥微粒，并通过中心复合设计进行优化。对喷雾干燥的未包衣和壳聚糖包衣微粒的各种参数（粒径、形态、药物包封率）进行表征。通过透析膜法在模拟阴道液中进行体外药物释放研究。通过MTT法进行体外研究以评估所开发制剂的细胞毒性潜力。使用瑞士白化小鼠的阴道组织通过Franz扩散池进行药物渗透性研究。
所有体外表征参数均达到最佳。体外释放研究表明符合Higuchi模型的控释。发现壳聚糖包衣微粒比未包衣微粒和平顺铂溶液具有更高的细胞毒性。发现壳聚糖包衣微粒比未包衣微粒具有更高的渗透性。最后，体内肿瘤消退和组织病理学研究证实了在不同时间间隔肿瘤体积显著减小。
因此，可以得出结论，黏膜黏附喷雾干燥微粒可以为通过阴道途径局部递送抗癌药物治疗宫颈癌提供一种有利的方法，其有效性得到增强。
