Bovine serum albumin nanoparticles encapsulating Dasatinib and Celecoxib for oral cancer: Preparation, characterization, and in-vitro evaluation.

Abstract

Oral squamous cell carcinoma is a diverse complex disease. Despite the ever-expanding repertoire of anti-cancer treatments, the outcomes are often inadequate highlighting the urgent need for innovative approaches. In this regard, co-targeting signaling pathways such as Src and COX-2 have attracted growing attention in several cancers, but co-inhibition of these two pathways using dasatinib and celecoxib has not been explored in oral cancer. However, the therapeutic efficacy of these drugs is limited due to their low aqueous solubility. Nanoencapsulation can improve this by utilizing naturally available proteins due to their ease of fabrication and biocompatibility. In this sense, this study aimed at preparing and characterizing dastatinib (DAS)/celecoxib (CXB)-loaded bovine serum albumin (BSA) nanoparticles as well as investigating their potential anticancer effects in vitro on SCC-4 oral cancer cell line. DAS/CXB-loaded BSA nanoparticles (NPs) were fabricated by the desolvation method, then characterized in terms of their hydrodynamic particle size, zeta potential, morphology and in vitro drug release. The IC50 was determined via the MTT assay. Cyclin D1, COX-2, p-Src and FAK protein expression levels were determined using ELISA while active caspase-3 was determined colorimetrically. DAS/CXB-loaded BSA NPs exhibited particle size of 336.6 ± 1.098 nm with low PDI value of 0.211 ± 0.019 and zeta potential of -35.0 ± 4.03 mV. Moreover, the in vitro cytotoxicity study revealed decreased IC50 value in case of the dual drug-loaded NPs compared to all treated groups, with significant decrease in the expression levels of cyclin D1, COX-2, p-Src and FAK proteins, besides, increased caspase-3 level. The findings suggest that DAS/CXB-loaded BSA NPs could serve as a drug delivery platform with increased antitumor effectiveness.