ABSTRACT
Vorinostat (VOR), a potent HDAC inhibitor, suffers from low solubility and poor absorption, which hinders its successful application in therapy, especially in the treatment of solid tumors. In this study, an effort to improve the physicochemical characteristics of VOR was made by encapsulating it in PEG-PLGA copolymeric micelles. VOR-loaded PEG-PLGA micelles (VOR-PEG-PLGA) were produced by thin-film hydration and physicochemically characterized. The PEG-PLGA micelles had an average size of 124.06 ± 2.6 nm, polydispersity index of 0.27 ± 0.1, and entrapment efficiency of 90 ± 2.1%. Micelles were characterized by TEM, DSC, and drug release studies. The drug release occurred in a sustained manner up to 72 h from PEG-PLGA micelles. In the in vitro cell-based studies using human breast cancer (MDA MB 231) and murine melanoma (B16F10) cell lines, VOR-PEG-PLGA micelles exhibited superior cellular internalization, enhanced cytotoxic activity, and greater apoptosis compared to free drug. Percent cell killing of 54.9% for VOR-PEG-PLGA-treated cells was observed after 24 h compared to 36% for free VOR in MDA MB 231 cell line. Further, significant tumor suppression was witnessed in B16F10 tumor-bearing mice treated with VOR-PEG-PLGA micelles with a 1.78-fold reduction in tumor volume compared to free VOR-treated animals. Overall, the VOR-PEG-PLGA micelles improved the biopharmaceutical properties of VOR, which resulted in enhanced anti-tumor efficacy. Therefore, the newly developed nano-formulation of VOR could be considered as an effective treatment option in solid tumors.
