title: Advanced polymeric matrix for valvular complications.
abstract: Poly(L-lactic acid) (PLLA) matrix systems incorporated with poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing nitric oxide (NO) donors (DETA NONOate) were developed for prevention of heart valve complications through sustained and controlled release of NO. PLLA matrices were prepared using the salt leaching method and the properties and drug release profiles were characterized. For assessment of the effects of PLLA systems on the pharmacological responses and cytotoxicity, various factors, such as calcium content, alkaline phosphatase (ALP) activity, cyclic guanosine monophosphate (cGMP) expression, intercellular adhesion molecule (ICAM-1) expression and cell viability of porcine aortic valve interstitial cells (PAVICs), were evaluated. PLLA matrices embedded with PLGA- NPs demonstrated its usefulness in alleviating the calcification rate of the VICs. The cGMP levels under osteoblastic conditions significantly increased, supporting that anticalcification activity of NO is mediated through NO-cGMP signaling pathway. The level of ICAM-1 expression in cells exposed to NO was lowered, suggesting that NO has an inhibitory activity against tissue inflammation. NO releases from PLLA matrix embedded with PLGA NPs prevented valvular calcification and inflammation without causing any cytotoxic activities. PLLA matrix system loaded with NPs containing NO donors could provide a new platform for sustained and controlled delivery of NO, significantly reducing valvular complications.
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64108, USA.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Acharya
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hopkins
authors.forename: Chi H
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001021:Aortic Valve / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002113:Calcification, Physiologic / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D016503:Drug Delivery Systems; D006350:Heart Valve Prosthesis; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019344:Lactic Acid / Q000494:pharmacology*; D053758:Nanoparticles / Q000648:ultrastructure; D009603:Nitroso Compounds / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity / Q000187:drug effects; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D009603:Nitroso Compounds; D018799:Intercellular Adhesion Molecule-1; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000469:Alkaline Phosphatase; D006152:Cyclic GMP