Evaluation of anticancer effects of Silibinin nanoparticles in B16 melanoma cell line

Abstract

Introduction: Silibinin, a non-toxic natural substance with a long history of medical uses, is a flavanone from Silybum marianum seeds. Silibinin has potent antioxidant effects and its anticancer activity has been shown in several in vivo and in vitro models. Silibinin is currently under phase II clinical trial in prostate cancer patients. One of the main advantages of silibinin is its safety and low toxicity in humans. Recent studies show that silibinin can enhance cytotoxic effects of chemotherapeutic agents in a variety of human cancers. However there is limited clinical application for silibinin because of its low bioavailability due to poor solubility. By using novel drug delivery systems like polymeric micelles poor solubility of natural substances like silibinin can be developed. Aim: The aim of this project was to develop silibinin loaded co-polymeric micelles and evaluate its growth inhibitory effects in B16 melanoma cells. Methods: Silibinin was loaded in poly (ethylene oxide)-block-poly (-caprolactone) (PEO-b-PCL) and poly (ethylene oxide)-block-poly(-benzyl carboxylate -caprolactone) (PEO-b-PBCL) micelles by co-solvent evaporation method. Silibinin loaded micelles were characterized for size and drug loading using light scattering (Zetasizer) and UV spectrophotometry, respectively. The growth inhibitory effect of micellar formulation was evaluated in B16 melanoma cell line using MTT assay. Results: Encapsulation of silibinin in PEO-b-PCL and PEO-b-PBCL by co-solvent evaporation technique resulted in polymeric micelles of < 90 nm in diameter. Silibinin was loaded in micelles with encapsulation efficiency being 47% and 95% for PEO-b-PCL and PEO-b-PBCL, respectively. The growth inhibitory effects of polymeric micellar silibinin were comparable with free drugs in B16 melanoma cell line in vitro Conclusion: These findings indicate the potential of PEO-b-PBCL polymeric micelles as suitable vehicles for silibinin.