Clinical use of calcitriol (1,25-dihydroxyvitamin D3) as an anticancer agent is currently limited by the requirement of supraphysiological doses and associated hypercalcemia. Nanoencapsulation of calcitriol is a strategy to overcome these drawbacks, allowing reduced administrated doses and/or frequency, while retaining the therapeutic activity towards cancer cells. For this purpose, we investigated the impact of calcitriol encapsulation on its antiproliferative activity and optimized formulation parameters with that respect. Calcitriol-loaded polymeric nanoparticles with different polymer:oil ratios were prepared by the nanoprecipitation method. Nanoparticles had similar mean size (200 nm) and EE (85%) whereas their release profile strongly depended on formulation parameters. Antiproliferative and cytotoxic activities of formulated calcitriol were evaluated in vitro using human breast adenocarcinoma cells (MCF-7) and showed that calcitriol-induced cell growth inhibition was closely related to its release kinetics. For the most suitable formulation, a sustained cell growth inhibition was observed over 10 days compared to free form. Advantages of calcitriol encapsulation and the role of formulation parameters on its biological activity in vitro were demonstrated. Selected nanoparticle formulation is a promising calcitriol delivery system ensuring a prolonged anticancer activity that could improve its therapeutic efficiency.
Keywords: Biodegradable polymeric nanoparticles; Calcitriol; Cancer; Drug delivery; MCF-7 cell line.
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