title: Biodegradable poly(lactic-co-glycolic acid) microspheres loaded with S-nitroso-N-acetyl-D-penicillamine for controlled nitric oxide delivery.
abstract: Nitric oxide (NO) is a fascinating and important endogenous free-radical gas with potent antimicrobial, vasodilating, smooth muscle relaxant, and growth factor stimulating effects. However, its wider biomedical applicability is hindered by its cumbersome administration, since NO is unstable especially in biological environments. In this work, to ultimately develop site-specific controlled release vehicles for NO, the NO donor S-nitroso-N-acetyl-D-penicillamine (SNAP) was encapsulated within poly(lactic-co-glycolic acid) 50:50 (PLGA) microspheres by using a solid-in-oil-in-water emulsion solvent evaporation method. The highest payload was 0.56(±0.01) μmol SNAP/mg microspheres. The in vitro release kinetics of the donor were controlled by the bioerosion of the PLGA microspheres. By using an uncapped PLGA (Mw=24,000-38,000) SNAP was slowly released for over 10days, whereas by using the ester capped PLGA (Mw=38,000-54,000) the release lasted for over 4weeks. The presence of copper ions and/or ascorbate in solution was necessary to efficiently decompose the released NO donor and obtain sustained NO release. It was also demonstrated that light can be used to induce rapid NO release from the microspheres over several hours. SNAP exhibited excellent storage stability when encapsulated in the PLGA microspheres. These new microsphere formulations may be useful for site-specific administration and treatment of pathologies associated with dysfunction in endogenous NO production, e.g. treatment of diabetic wounds, or in diseases involving other biological functions of NO including vasodilation, antimicrobial, anticancer, and neurotransmission.
authors.affiliation: Department of Chemistry, The University of Michigan, 930 N. University, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, The Biointerfaces Institute, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109, USA.
authors.forename: Gergely
authors.initials: G
authors.lastname: Lautner
authors.affiliation: Department of Chemistry, The University of Michigan, 930 N. University, Ann Arbor, MI 48109, USA. Electronic address: mmeyerho@umich.edu.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Meyerhoff
authors.affiliation: Department of Pharmaceutical Sciences, The Biointerfaces Institute, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109, USA. Electronic address: schwende@med.umich.edu.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Schwendeman
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D009569:Nitric Oxide / Q000737:chemistry; D020030:Nitric Oxide Donors / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D026423:S-Nitroso-N-Acetylpenicillamine / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D020030:Nitric Oxide Donors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D009569:Nitric Oxide; D019344:Lactic Acid; D026423:S-Nitroso-N-Acetylpenicillamine
keywords: Biodegradable polymers; Controlled release; Nitric oxide; Poly(lactic-co-glycolic acid); Snitroso-N-acetyl-D-penicillamine