title: Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity.
abstract: 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.
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Hasan
authors.initials: H
authors.lastname: Nurhasni
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Cao
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Moonjeong
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Polymer Science and Engineering, Pusan National University, Busan, South Korea.
authors.forename: Il
authors.initials: I
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Bok Luel
authors.initials: BL
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Pusan National University, Busan, South Korea.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Yoo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002460:Cell Line; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D009569:Nitric Oxide; D019344:Lactic Acid; D011094:Polyethyleneimine
keywords: PEI; PLGA; antimicrobial; nitric oxide-releasing nanoparticles; wound healing