Abstract

Objective: The aim of this study was to improve the oral solubility of Pemigatinib and Entrectinib through incorporation into nanosponges (NSs), and further the cytotoxic potential of optimized formulations of NSs on A498, MCF-7, and PANC-1 cell lines in the MTT based Cell proliferation assay was analyzed. Methods: In the current study Pemigatinib and Entrectinib were formulated in to NS tablets and cytotoxicity was determined by using A498, MCF-7, and PANC-1 cell lines. The optimized NS formulation was determined prepared into a tablet dosage form, which further was evaluated for physical parameters and in vitro drug release study. For cytotoxicity studies, MTT assay was conducted for these formulations, IC50 values were calculated for the tested compound and compared with 5-Fluorouracil. Results: The optimized formulation was evaluated for physical parameters and in vitro drug release study, the results were satisfactory. The IC50 of Entrectinib NS, Pemigatinib NS and 5-Fluorouracil, against A498 cell line was 26.34, 85.24 and 15.24 µg/ml, respectively. The IC50 of Entrectinib NS, Pemigatinib NS and 5-Fluorouracil, against MCF-7 cell line was 71.54, 35.48 and 24.56 µg/ml, respectively. The IC50 of Entrectinib NS, Pemigatinib NS and 5-Fluorouracil, against PANC-1 cell line was 35.14, 22.54 and 22.54 µg/ml, respectively. It was observed that the IC50 of drug-loaded NS was higher than the comparator drug and these enter the cells by active transport and induce cytotoxicity to the cells. Conclusion: The overall results from the studies suggest that Entrectinib NS and Pemigatinib NS provided efficient cytotoxic effects, which could play a significant role in the percentage cell death.

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