title: Formulation and in vitro evaluation of niacin-loaded nanoparticles to reduce prostaglandin mediated vasodilatory flushing.
abstract: OBJECTIVE
  Niacin, activating G-protein coupled receptor (GPR) 109A, stimulates release of vasodilatory prostaglandins (PGs) such as PGE2 which can elicit niacin-associated flushing side effects. Poly-lactic-co-glycolic 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 PGE2 expression in whole human blood as a model for niacin-induced flushing.
  
  
  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 PGE2 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 PGE2 release (p < 0.05).
  
  
  CONCLUSIONS
  These results support the use of PLGA-NPs as a novel method of delivery for reducing niacin-associated flushing.
authors.affiliation: Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, USA. harirfor@etsu.edu.
authors.forename: D L
authors.initials: DL
authors.lastname: Cooper
authors.forename: J A
authors.initials: JA
authors.lastname: Carmical
authors.forename: P C
authors.initials: PC
authors.lastname: Panus
authors.forename: S
authors.initials: S
authors.lastname: Harirforoosh
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods; D005483:Flushing / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D009525:Niacin / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011453:Prostaglandins / Q000097:blood* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D011453:Prostaglandins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D009525:Niacin; D019344:Lactic Acid