Formulation and evaluation of drug-loaded targeted magnetic microspheres for cancer therapy

Gerald G Enriquez,¹ Syed AA Rizvi,² Martin J D’Souza,³ Duc P Do<sup>1

1</sup>Department of Pharmaceutical Sciences, College of Pharmacy, Chicago State University, Chicago, IL, ²Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, ³Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA, USA

Abstract: Enhanced and targeted drug delivery using biodegradable microspheres is emerging as a promising approach for cancer therapy. The main objective of the present research was to formulate, characterize, and evaluate iron oxide (magnetic) containing a bovine serum albumin-based microsphere drug delivery system, capable of efficiently delivering sulforaphane, a histone deacetylase inhibitor, for an extended period of time in vivo. Magnetic microspheres were prepared by spray-drying and characterized for their physicochemical properties and dissolution profile. Further, they were evaluated for therapeutic efficacy in in vitro and in vivo systems. In vitro studies in B16 melanoma cells revealed that there was about 13%–16% more inhibition of cell viability when either 30 µM or 50 µM of sulforaphane was used with iron oxide in the polymeric carrier. Data from in vivo studies in C57BL/6 mice revealed that the magnetic microspheres (localized to the tumor site with the help of a strong magnet) inhibited 18% more tumor growth as compared with sulforaphane in solution. In addition, there was a 40% reduction in histone deacetylation levels in mice treated with iron oxide microspheres containing sulforaphane. Thus, magnetic microspheres are shown to be an effective drug delivery system for anticancer drugs.

Keywords: sulforaphane, delivery system, epigenetic therapy, microspheres, histone deacetylase inhibitor, iron oxide