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Nano-encapsulation of vitamin D3 active metabolites for application in chemotherapy: formulation study and in vitro
Eyad Almouazen1, Sandrine Bourgeois, Lars Petter Jordheim
1University Lyon, University Claude Bernard Lyon 1 Laboratoire d'Automatique et de Génie des Procédés, LAGEP UMR CNRS 5007, CPE-308 G, 43 bd. 11 Nov.1918, 69622, Villeurbanne, France.
Purpose:
Calcitriol (1,25-dihydroxyvitamin D3), the active metabolite of vitamin D3, is a potential anticancer agent but with high risk of hypercalcemia which limits the achievement of effective serum concentrations. Thus, calcitriol targeting delivery by nanoparticles may present a good solution.
Methods:
Vitamin D3 active metabolites were encapsulated into polymeric nanoparticles and different formulation parameters were tested. The growth inhibitory efficiency of these nanoparticles was carried out in vitro on human breast adenocarinoma cells (MCF-7).
Results:
Using cholecalciferol (the inactive metabolite), different polymer and oil ratios were compared to select nanoparticles presenting high encapsulation efficiency and sustained release profile. Calcidiol/calcitriol loaded nanoparticles had good encapsulation efficiencies (around 90%) associated with sustained releases over 7 days and enhanced stability. Moreover, loaded nanoparticles showed similar growth inhibition to non-encapsulated metabolites of vitamin D3 on day 4 and higher activities on days 7 and 10 after treatment initiation.
Conclusion:
The nano-encapsulation of vitamin D3 active metabolites may offer a new and potentially effective strategy for vitamin D3-based chemotherapy overcoming its actual limitations. The targeting delivery of vitamin D3 metabolites should be encouraged.
