Development of carboplatin loaded bovine serum albumin nanoparticles and evaluation of its effect on an ovarian cancer cell line

Abstract

Ovarian cancer has the highest mortality rate among gynecological cancers. It requires urgent therapy, but standard treatments are not sufficient to cure ovarian cancer completely. Chemotherapy has critical side effects due to non-specific toxicity. In this regard, nanoparticulate drug delivery systems, one of the most promising therapeutic approaches, have been developed for cancer therapy. The main objective of the present research was to develop novel bovine serum albumin (BSA) nanoparticle formulation encapsulating carboplatin (CRB) and to evaluate its anti-cancer activity against A2780 human ovarian cancer cell line. CRB-loaded BSA nanoparticles were prepared using a desolvation method and characterized by several physicochemical properties, including encapsulation efficiency, particle size and size distribution, surface charge, particle morphology, thermal behavior. Different CRB-loaded BSA nanoparticles were prepared using 33 factorial design in which varying the BSA concentration, ethanol/BSA solution ratio and glutaraldehyde/BSA ratio as three factors. The effects of these factors on the particle size, polydispersity index and encapsulation efficiency were evaluated to produce an optimized nanoformulation. Based on dependent variables, the formulation including 3% BSA concentration, 4/1 (v/v) ethanol/BSA solution ratio (v/v), 7.80 μg/mg glutaraldehyde/BSA ratio was selected as optimum. It was found to have spherical shapes with negative surface charges and about 253 nm particle size with a low polydispersity index indicating a narrow particle size distribution. According to the confocal laser microscopy and flow cytometer studies, it exhibited a high uptake into A2780 cells. In addition, cytotoxicity experiments revealed that CRB-loaded albumin nanoparticles showed more potent anti-cancer effect on A2780 ovarian cancer cell line with approximately 2-fold lower IC50 value, compared with free CRB.