Pelegrino Milena T, De Araujo Lima Bruna, Do Nascimento Mônica H M, Lombello Christiane B, Brocchi Marcelo, Seabra Amedea B
Center for Natural and Human Sciences, Universidade Federal do ABC, Av. dos Estados 5001, Santo André, SP, CEP 09210-580, Brazil.
Nanomedicine Research Unit (NANOMED), Universidade Federal do ABC, Av. dos Estados 5001, Santo André, SP 09210-580, Brazil.
Polymers (Basel). 2018 Apr 18;10(4):452. doi: 10.3390/polym10040452.
Nitric oxide (NO) is involved in physiological processes, including vasodilatation, wound healing and antibacterial activities. As NO is a free radical, designing drugs to generate therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor -nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL)-chitosan (CS) hydrogel, with an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL of hydrogel, which corresponds to 1 mmol·L of GSNO). Interestingly, the concentration range in which the NO-releasing hydrogel demonstrated an antibacterial effect was not found to be toxic to the Vero mammalian cell. Thus, the GSNO-PL/CS hydrogel is a suitable biomaterial for topical NO delivery applications.
一氧化氮(NO)参与多种生理过程,包括血管舒张、伤口愈合和抗菌活性。由于NO是一种自由基,设计能够以可控的空间和时间方式产生治疗量NO的药物仍然是一项挑战。在本研究中,采用一种简便且经济可行的方法,将NO供体——亚硝基谷胱甘肽(GSNO)掺入热响应性泊洛沙姆F-127(PL)-壳聚糖(CS)水凝胶中。CS是一种具有已知抗菌特性的多糖。使用扫描电子显微镜、流变学和差示扫描量热法技术对水凝胶进行表征。结果表明,该水凝胶具有光滑的表面、热响应行为和良好的机械稳定性。含GSNO的PL/CS水凝胶中NO释放和GSNO扩散的动力学表明,其能够持续释放NO/GSNO,释放浓度适合生物医学应用。GSNO-PL/CS水凝胶对Vero细胞表现出浓度依赖性毒性,并对(水凝胶最低抑菌浓度和最低杀菌浓度值为0.5μg·mL,相当于1mmol·L的GSNO)具有抗菌活性。有趣的是,发现释放NO的水凝胶表现出抗菌作用的浓度范围对Vero哺乳动物细胞无毒。因此,GSNO-PL/CS水凝胶是一种适用于局部递送NO的生物材料。