Formulation and in vitro evaluation of niacin-loaded nanoparticles to reduce prostaglandin mediated vasodilatory flushing.

OBJECTIVE: Niacin, activating G-protein coupled receptor (GPR) 109A, stimulates release of vasodilatory prostaglandins (PGs) such as PGE(2) which can elicit niacin-associated flushing side effects. Poly-lactic-coglycolic acid (PLGA) and poly-lactic acid (PLA) are used in nanoparticle (NP) drug delivery to reduce adverse effects and modulate drug release. Our study evaluated the in vitro effects of niacin-loaded PLGA or PLA-NPs on PGE(2) expression in whole human blood as a model for niacin-induced flushing. MATERIALS AND METHODS: NPs were formulated using a solvent evaporation process and characterized by size, polydispersity, zeta potential, drug entrapment, morphology, and drug release. NP in vitro effects on PGE(2) release were measured via ELISA analysis. RESULTS: PLGA-NPs demonstrated the lowest NP size (66.7 +/- 0.21 nm) with the highest zeta potential and percent drug entrapment (42.00 +/- 1.62 mV and 69.09 +/- 0.29%, respectively) when compared to PLA-NPs (130.4 +/- 0.66 nm, 27.96 +/- 0.18 mV, 69.63 +/- 0.03 %, respectively). In vitro release studies showed that PLGA-NPs underwent significant reductions in cumulative drug release when compared to PLA-NPs (p < 0.05). Furthermore, when compared to plain niacin, PLGA-NPs significantly reduced in vitro PGE(2) release (p < 0.05). CONCLUSIONS: These results support the use of PLGA-NPs as a novel method of delivery for reducing niacin-associated flushing.