Pharmacological applications of nitric oxide-releasing biomaterials in human skin
In recent decades, nitric oxide (NO) has emerged as a new drug for healing infected wounds due to its beneficial effects in regulating inflammation and promoting wound healing processes such as cell proliferation and tissue remodeling. In addition to its ability to promote wound healing, NO has broad antibacterial activity, which may be a desirable property for treating infected wounds. Through the formation of reactive nitrogen species or direct nitrosation, NO can damage bacterial cell membranes, proteins, and DNA, causing bacterial cell death. Multiple antibacterial mechanisms enable NO to exert antibacterial effects against drug-resistant strains, including MRSA. Moreover, the development and survival of tolerance to NO requires the accumulation of multiple favorable mutations over multiple generations, which seems rather remote. Taken together, NO-based formulations appear to be desirable therapeutic modalities for the treatment of infected skin wounds. Furthermore, advances in nanotechnology that have been utilized to enhance therapeutic efficacy have led to the recent development of many NO-releasing nanoparticle formulations, including polyethylenimine NONOate-doped PLGA nanoparticles, NO-releasing silica nanoparticles, and NO-releasing metal nanoparticles. Shows enhanced antibacterial and wound healing activity. However, these NO-releasing nanoparticle formulations have met with limited success as most are composed of non-biodegradable materials such as polyethylenimine and heavy metals that can accumulate in skin tissue. To avoid potential toxicity, the development of NO-releasing nanoparticles composed of biocompatible materials is highly desirable. After preparation of the GPNPs, scanning electron microscopy was performed to examine their morphology. A Zetasizer Nano ZS90 was used to measure the hydrodynamic particle size and zeta potential of GPNP. GPNP loading efficiency was measured using a Sievers nitric oxide analyzer. The device was calibrated with NO free air and a 45 ppm NO gas standard. NO gas released from the medium was carried to the apparatus by Ar gas at a flow rate of 80 ml/min. Nitric oxide (NO) is a key component of host defense against pathogen invasion. However, its therapeutic utility is limited due to the lack of a practical delivery system. Recently, an NO-releasing nanoparticle platform (NO-np) was shown to have broad-spectrum antibacterial activity in vitro and preclinically in vivo in skin abscess models. To extend these results, both topical (TP) and intralesional (IL) NO-np administration were evaluated in a mouse intramuscular abscess MRSA model and compared to vancomycin. All treatment groups facilitated abscess clearance by clinical, histological, and microbiological examination on both days 4 and 7 after infection. However, abscesses treated with NO-np by both routes showed a more substantial and statistically significant reduction in bacterial viability based on colony-forming unit assays, and histologically showed inflammatory cell infiltration. Less, indicating preservation of muscle structure. These data suggest that NO-np may be an effective addition to defenses against deep soft tissue infections. Myositis suppurativa is a suppurative infection of large skeletal muscles with no apparent cause in adjacent structures. Although several other muscle infections have been reported, the most commonly affected muscles are the thigh and buttock muscles. The frequency of muscle abscesses has increased in recent years. Staphylococcus aureus Methicillin-resistant Staphylococcus aureus (MRSA)-associated myositis pyogenes has been increasingly reported to date, and inappropriate use of broad-spectrum antibiotics has led to many antibiotic-resistant infections. The emergence of strains is further encouraged.