In vitro and in vivo evaluation of a novel nitric oxide-releasing ointment for the treatment of methicillin-resistant St
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Journal of Pharmaceutical Investigation https://doi.org/10.1007/s40005-020-00472-1
ORIGINAL ARTICLE
In vitro and in vivo evaluation of a novel nitric oxide‑releasing ointment for the treatment of methicillin‑resistant Staphylococcus aureus‑infected wounds Juho Lee1 · Shwe Phyu Hlaing1 · Jiafu Cao1 · Nurhasni Hasan1 · Jin‑Wook Yoo1 Received: 26 November 2019 / Accepted: 5 February 2020 © The Korean Society of Pharmaceutical Sciences and Technology 2020
Abstract Purpose Nitric oxide (NO) has emerged as a novel agent for the treatment of infected wounds owing to its potent woundhealing effects and antibacterial activity against drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we developed a NO-releasing ointment composed of S-nitrosoglutathione (GSNO) and polyethylene glycol (PEG) for the treatment of MRSA-infected cutaneous wounds. Methods The GSNO-incorporated PEG ointment (GPO) was successfully prepared by homogeneous dispersion of micronized GSNO in a PEG ointment base. High encapsulation efficiency was achieved (97.25%) via water-free fabrication processing of the GPO, resulting in minimal GSNO hydrolysis. Results When applied to a wound, the wound fluid triggered the degradation of GSNO and NO was released from the GPO for 24 h without an initial burst release. The GPO exhibited potent antibacterial effects against MRSA without cytotoxic effects against L929 cells. An in vivo wound healing experiment using a mouse MRSA-challenged full-thickness wound model revealed that the GPO could facilitate healing of infected wounds. Conclusion Thus, the GPO could be a promising NO-releasing formulation for the treatment of infected cutaneous wounds. Keywords Nitric oxide · S-nitrosoglutathione · Methicillin-resistant staphylococcus aureus · Infected wound healing · Ointment
Introduction Cutaneous wound infections remain a global problem, and their treatment costs millions of dollars per year (Daeschlein 2013). In addition, wound infections can cause severe complications, including sepsis, the mortality due to which is greater than 30% in the United States (Fleischmann et al. 2016). Wound healing occurs spontaneously through three sequential phases: inflammation, cell proliferation, and tissue remodeling (Bello and Phillips 2000; Witte and Barbul 1997); however, wounds are frequently contaminated by various bacteria that induce continuous inflammation at the wound site (Yurt et al. 1984). Due to the chronic inflammation caused by the bacteria, the healing process of an * Jin‑Wook Yoo [email protected] 1
College of Pharmacy, Pusan National University, Busan 609‑735, South Korea
infected wound is stalled at the inflammatory phase, resulting in delayed wound healing. For these reasons, eradication of bacteria from the wound is essential for successful treatment (Choi et al. 2019). For the treatment of infected wound, antibacterial ointments are widely used for the treatment of infected wounds as these are easily applied to bendable areas of the human body an
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