Optimized PEGylated cubosomes: A novel approach for specific delivery of Dacomitinib to non-small cell lung cancer.

Abstract

Dacomitinib (DM), a newly FDA-approved chemotherapeutic agent, demonstrates remarkable selectivity in combating non-small cell lung cancer (NSCLC) and hindering its fierce metastasis. The study intended to engineer pH-triggered drug-release PEGylated cubosomes for delivery of DM to ameliorate its targeting potential with minimal side effects. Eight PEGylated cubosomal dispersions were prepared by emulsification method using a 23 full factorial design. The prepared dispersions were characterized for particle size, entrapment efficiency, zeta potential, and drug release in pH 7.4 and 5.5. The optimized formula was subjected to further investigations such as XRD, DSC, TEM, FTIR, in vitro cytotoxicity, cellular uptake, and flowcytometry. The optimum DM-loaded PEGylated cubosomes displayed a mean particle size of 214.30 ± 0.41 nm, PDI of 0.231± 0.001, and 95.04 ± 0.40 % drug entrapment efficiency. The cumulative % release of DM after 24 h in pH 7.4 and 5.5 was 6.30 ± 0.33 and 70.00 ± 1.01 % respectively confirming pH triggered release. In vitro-cytotoxicity study highlighted the powerful cytotoxic effect of DM-loaded PEGylated cubosomes against the H-1975 cell line as indicated by a significantly (P < 0.05) reduced IC50 value by approximately 7.70-fold compared to pure DM. The overall cellular uptake of DM-loaded PEGylated cubosomes was immensely significant compared to a negligible of the free drug in addition to causing cell apoptotic death at the G1/S phase. The results demonstrated that DM-loaded PEGylated cubosomes could be ranked as an efficiently selective delivery system for transporting DM to human lung cancer mutant cell line.