Soriano José L, Calpena Ana C, Rodríguez-Lagunas María J, Domènech Òscar, Bozal-de Febrer Nuria, Garduño-Ramírez María L, Clares Beatriz
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain.
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
Pharmaceutics. 2020 Dec 22;13(1):8. doi: 10.3390/pharmaceutics13010008.
The main goal of this work is the study of the skin wound healing efficacy of an antioxidant cocktail consisting of vitamins A, D, E and the endogenous pineal hormone melatonin (MLT), with all of these loaded into a thermosensitive hydrogel delivery system. The resulting formulation was characterized by scanning electron microscopy. The antioxidant efficacy and microbiological activity against Gram positive and Gram negative strains were also assayed. The skin healing efficacy was tested using an in vivo model which included histological evaluation. Furthermore, atomic force microscopy was employed to evaluate the wound healing efficacy of rat skin burns through the determination of its elasticity at the nanoscale using force spectroscopy analysis. The resulting hydrogel exhibited sol state at low temperature and turned into a gel at 30 ± 0.2 °C. The hydrogel containing the antioxidant cocktail showed higher scavenging activity than the hydrogel containing vitamins or MLT, separately. The formulation showed optimal antimicrobial activity. It was comparable to a commercial reference. It was also evidenced that the hydrogel containing the antioxidant cocktail exhibited the strongest healing process in the skin burns of rats, similar to the assayed commercial reference containing silver sulfadiazine. Histological studies confirmed the observed results. Finally, atomic force microscopy demonstrated a similar distribution of Young's modulus values between burned skin treated with the commercial reference and burned skin treated with hydrogel containing the antioxidant cocktail, and all these with healthy skin. The use of an antioxidant cocktail of vitamins and MLT might be a promising treatment for skin wounds for future clinical studies.
这项工作的主要目标是研究一种由维生素A、D、E和内源性松果体激素褪黑素(MLT)组成的抗氧化剂混合物的皮肤伤口愈合功效,所有这些成分都负载于一种热敏水凝胶递送系统中。通过扫描电子显微镜对所得制剂进行表征。还测定了其对革兰氏阳性和革兰氏阴性菌株的抗氧化功效及微生物活性。使用包括组织学评估在内的体内模型测试皮肤愈合功效。此外,采用原子力显微镜通过力谱分析在纳米尺度上测定大鼠皮肤烧伤的弹性来评估伤口愈合功效。所得水凝胶在低温下呈现溶胶状态,在30±0.2°C时转变为凝胶。含有抗氧化剂混合物的水凝胶比分别含有维生素或MLT的水凝胶表现出更高的清除活性。该制剂显示出最佳的抗菌活性,与商业参比制剂相当。还证明含有抗氧化剂混合物的水凝胶在大鼠皮肤烧伤中表现出最强的愈合过程,类似于所测定的含磺胺嘧啶银的商业参比制剂。组织学研究证实了观察结果。最后,原子力显微镜显示,用商业参比制剂处理的烧伤皮肤和用含有抗氧化剂混合物的水凝胶处理的烧伤皮肤之间,以及所有这些与健康皮肤之间,杨氏模量值分布相似。使用维生素和MLT的抗氧化剂混合物可能是未来临床研究中治疗皮肤伤口的一种有前景的方法。