Drug Targeting of Cisplatin Loaded Immunomicrospheres of PLGA with Rabbit Antimouse IgG in Chemotherapy of DLA Tumour

Abstract

The normal- cell toxicity in cancer chemotherapy outweighing the anticancer potential is well known. Therefore the present search was undertaken to develop ligand carrier mediated formulations to deliver cisplatin (CDDP) to enhance the cytotoxic action in cancer cells with simultaneous reduction in nephrotoxicity. The aim of targeting drugs to diseased tissue is to deliver a large amount of drug in one bolus dose that can be released in small sustained amounts directly to the tumour cells, thus minimizing the toxic effect of the drugs on normal tissue. When microspheres were specifically targeted to the tumour cells, the cytotoxic efficacy of the system was greatly enhanced. A possible explanation for these results is that the close association between immunomicrospheres and the tumour cells increases the likelihood that the drugs would reach the surface of the tumour cells and enter through the cell membrane to induce cell death. The objectives of preparing biodegradable poly (d,l,lactide co-glycolide) microspheres loaded with cisplatin, characterizing and evaluating the different batches of microspheres, preparing immunomicrospheres and to evaluate comparatively the anti tumour activity of the microspheres and immunomicrospheres against DLA in vitro and in vivo, and evaluating the anticancer activity of the optimized batch of microspheres in MC7 breast cancer cell line and HeLa cell line. The results of cellular viability as assessed by MTT assay in human cervical cancer cell line (HeLa) and breast cancer MCF7 cell line demonstrate a more pronounced anti proliferative activity by immunomicrospheres compared to microspheres of CDDP. With these results of in vitro cytotoxic assays in DLA cells, human cervical cancer HeLa cell line, breast cancer MCF7 cell line and of in vivo studies on DLA bearing mice, we can conclude that the developed biodegradable PLGA microspheres and immunomicrospheres loaded with cisplatin will be useful formulations via intratumoural administration due to controlled and targeted delivery.