Biodegradable poly(lactic-co-glycolic acid) microspheres loaded with S-nitroso-N-acetyl-D-penicillamine for controlled nitric oxide delivery
Open accessAbstract
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.
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PELA and PLGA are suitable vehicles for encapsulating NO donors to prolong NO release.
“Biodegradable poly(ethylene oxide-co-lactic acid) (PELA)249 and poly(lactic-co-glycolic acid) (PLGA)206,219,249 have also been shown to be suitable vehicles for encapsulating NO donors to prolong the NO release.”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [206]
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- Authors
- Lautner, G., Meyerhoff, M. E., & Schwendeman, S. P.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Meyerhoff, Mark E.
- Schwendeman, Steven P.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 225
- Pages
- 133-139
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC4769910
- OpenAlex
- W2228111974
- Cited by
- 70
- References
- 42
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 9 · 2021: 9 · 2020: 6 · 2019: 7 · 2018: 10 · 2017: 3 · 2016: 2
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (EB000783)
- The University of Michigan MCubed program
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- nitric oxide delivery, PLGA microspheres, controlled release, biodegradable drug delivery, emulsion solvent evaporation, PLGA molecular weight, vitamin C, light-triggered release, storage stability, diabetic wound healing, vasodilation
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Delayed-Action Preparations, Microspheres, Nitric Oxide, Polyglycolic Acid, Drug Delivery Systems, Lactic Acid, Nitric Oxide Donors, S-Nitroso-N-Acetylpenicillamine
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