Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity
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Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections.
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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 [219]
Yoo and coworkers developed PLGA nanoparticles with diazeniumdiolated PEI for long-term NO release for antimicrobial applications.
“Yoo and coworkers developed PLGA (5050DLG5E) nanoparticles (NO/PPNPs) with diazeniumdiolated polyethylenimine (PEI) for long term NO release for antimicrobial applications.219”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [219]
NO possesses broad-spectrum antibacterial activity against both gram-positive and gram-negative bacteria, including MRSA.
“Of note, NO possesses broad-spectrum antibacterial activity against both gram-positive and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).219,281”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [219]
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- Authors
- Yoo, J.-W., Nurhasni, H., Cao, J., Choi, M., Kim, I., Lee, B. L., & Jung, Y.
- Affiliations
- Pusan National University (KR)
- Corresponding author
- Yoo, Jin-Wook
- Venue
- International Journal of Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2015-04
- Volume
- 10
- Pages
- 3065
- ISSN
- 1176-9114 (ISSN-L)
- 1178-2013
- PMC
- PMC4411019
- OpenAlex
- W2100509378
- Cited by
- 131
- References
- 43
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 3 · 2022: 12 · 2021: 24 · 2020: 17 · 2019: 19 · 2018: 17 · 2017: 16 · 2016: 10 · 2015: 1
- FWCI
- 14.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Nanomedicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Hasanuddin University Repository (submittedVersion)
- Funders
- National Research Foundation
- National Research Foundation of Korea
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Keywords
- poly(lactic-co-glycolic acid), polyethyleneimine, diazeniumdiolates, antibacterial activity, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, MRSA-infected wounds, wound healing, re-epithelialization, antibiotic resistance, skin infections, fibroblast cytotoxicity
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Anti-Bacterial Agents, Bacteria, Cell Line, Nitric Oxide, Polyethyleneimine, Polyglycolic Acid, Wound Healing, Lactic Acid, Mice, Nanoparticles
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