Biodegradable poly(lactic-co-glycolic acid) microspheres loaded with S-nitroso-N-acetyl-D-penicillamine for controlled nitric oxide delivery

JOURNAL OF CONTROLLED RELEASE

卷:225

Article

Lautner, Gergely^1,2  Meyerhoff, Mark E.¹  Schwendeman, Steven P.^2,3 

[1] Univ Michigan, Dept Chem, 930 N Univ, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Biointerfaces Inst, Dept Pharmaceut Sci, 2800 Plymouth Rd, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Biomed Engn, 2800 Plymouth Rd, Ann Arbor, MI 48109 USA

关键词: Biodegradable polymers;    Nitric oxide;    Controlled release;    Snitroso-N-acetyl-D-penicillamine;    Poly(lactic-co-glycolic acid);   

DOI  :  10.1016/j.jconrel.2015.12.056

来源: Elsevier

【 摘 要 】

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) mu mol 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 10 days, whereas by using the ester capped PLGA (Mw = 38,000-54,000) the release lasted for over 4 weeks. The presence of copper ions and/or ascorbate in solution was necessary to efficiently decompose the released NO donor and obtain sustained NO release. Itwas 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. (C) 2016 Elsevier B.V. All rights reserved.

【 授权许可】

Free