Optimized PEGylated cubosomes: a novel approach for specific delivery of dacomitinib to non-small cell lung cancer cells

Abstract

Dacomitinib (DM), a newly FDA-approved chemotherapeutic agent, demonstrates remarkable selectivity in combating non-small cell lung cancer (NSCLC) and hindering its severe metastasis. This study aimed to engineer pH-triggered drug-release of PEGylated cubosomes for the delivery of DM to improve its targeting potential with minimal side effects. Eight PEGylated cubosomal dispersions were prepared using the emulsification method using a 2³ full factorial design. The prepared dispersions were characterized for their particle size, entrapment efficiency, zeta potential, and drug release at 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 flow cytometry. The optimum DM-loaded PEGylated cubosomes displayed a mean particle size of 214.30 ± 0.41 nm, PDI of 0.231 ± 0.001, and drug entrapment efficiency of 95.04% ± 0.40%. The cumulative % release of DM after 24 h at 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 potent 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 with that of pure DM. The overall cellular uptake of DM-loaded PEGylated cubosomes was immensely significant compared with a negligible uptake of the free drug, in addition to causing apoptotic cell death in the G1/S phase. Results demonstrated that DM-loaded PEGylated cubosomes could be ranked as an efficiently selective delivery system for transporting DM to a human lung cancer mutant cell line.