Programa de pós-graduação em Ciências Veterinárias, Departamento de Ciências Veterinárias, Centro de Ciências Agrárias e Engenharias, Universidade Federal do Espírito Santo - UFES, 29.500-000, Alegre, ES, Brazil.
Laboratório de Produção Farmacêutica, Departamento de Farmácia e Nutrição, Centro de Ciências Exatas, Naturais e da Saúde, Universidade Federal do Espírito Santo - UFES, 29.500-000 Alegre, ES, Brazil.
Mater Sci Eng C Mater Biol Appl. 2020 Apr;109:110643. doi: 10.1016/j.msec.2020.110643. Epub 2020 Jan 7.
Chronic wounds constitute a serious public health problem, and developing pharmaceutical dosage forms to ensure patient comfort and safety, as well as optimizing treatment effectiveness, are of great interest in the pharmaceutical, medical and biomaterial fields. In this work, the preparation of films based on blends of poly(vinyl alcohol), starch and poly(acrylic acid), polymers widely used as pharmaceutical excipients, and pomegranate peel extract (PPE), a bioactive compound with antimicrobial and healing activities relevant to the use as a bioactive wound dressing, was proposed. Initially, the minimum inhibitory concentration (MIC) of the PPE was investigated by an in vitro method. Then, the best concentration of the PPE to be used to prepare the films was researched using an antimicrobial susceptibility test with the disc diffusion method. The microbiological assay was performed in films prepared by the solvent casting method in the presence of two concentrations of PPE: 1.25% w/v and 2.5% w/v. Films containing the lower PPE concentration showed antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis, with a difference that was not considered statistically significant when compared to the higher concentration of the extract. Therefore, the films prepared with the lower proportion of PPE (1.25% w/v) were considered for the other studies. The miscibility and stability of the extract in the films were investigated by thermal analysis. Parameters that determine the barrier properties of the films were also investigated by complementary techniques. Finally, in vitro biological tests were performed for safety evaluation and activity research. Analysis of the results showed that the incorporation of the higher proportion of starch in the blend (15% v/v) (PVA:S:PAA:PPE4) yielded smooth, transparent, and domain-free films without phase separation. Additionally, the PVA:S:PAA:PPE4 film presented barrier properties suitable for use as a cover. These films, when subjected to the in vitro hemolytic activity assay, were nonhemolytic and biocompatible. No toxicity from the extract was observed at the concentrations studied. The results of the wound healing in vitro test showed that films containing 1.25% PPE are efficient in reducing the scratch open area, provoking almost total closure of the scratches within 48 h without cytotoxicity.
慢性伤口是一个严重的公共卫生问题，开发确保患者舒适和安全的药物剂型，以及优化治疗效果，在制药、医疗和生物材料领域都具有重要意义。在这项工作中，制备了基于聚乙烯醇、淀粉和聚丙烯酸共混物的薄膜，这些聚合物广泛用作药物赋形剂，以及石榴皮提取物（PPE），一种具有抗菌和愈合活性的生物活性化合物，与用作生物活性伤口敷料的用途相关。最初，通过体外方法研究了 PPE 的最小抑菌浓度（MIC）。然后，通过使用圆盘扩散法进行的抗菌药敏试验研究了用于制备薄膜的最佳 PPE 浓度。微生物测定是在存在两种浓度的 PPE（1.25%w/v 和 2.5%w/v）的溶剂浇铸法制备的薄膜中进行的。含有较低 PPE 浓度的薄膜对金黄色葡萄球菌和表皮葡萄球菌表现出抗菌活性，与提取物较高浓度相比，差异不具有统计学意义。因此，考虑使用较低比例的 PPE（1.25%w/v）制备薄膜进行其他研究。通过热分析研究了提取物在薄膜中的混溶性和稳定性。还通过补充技术研究了决定薄膜阻隔性能的参数。最后，进行了体外生物试验以进行安全性评估和活性研究。结果分析表明，在共混物中加入较高比例的淀粉（15%v/v）（PVA：S：PAA：PPE4）可得到无相分离的光滑、透明且无畴的薄膜。此外，PVA：S：PAA：PPE4 薄膜具有适合用作覆盖物的阻隔性能。这些薄膜在进行体外溶血活性测定时是非溶血的且具有生物相容性。在所研究的浓度下，未观察到提取物的毒性。体外伤口愈合试验的结果表明，含有 1.25%PPE 的薄膜能够有效减少划痕开口面积，在没有细胞毒性的情况下，在 48 小时内几乎完全封闭划痕。
