Department of Chemistry, Faculty of Science, Menoufia University, Egypt.
Aachen-Maastricht Institute for Biobased Materials, Faculty of Science and Engineering, Maastricht University, The Netherlands.
J Mater Chem B. 2023 Aug 2;11(30):7144-7159. doi: 10.1039/d3tb00926b.
Microbial infection is the most common obstacle in the wound healing process, leading to wound healing impairment and complications and ultimately increasing morbidity and mortality. Due to the rising number of pathogens evolving resistance to the existing antibiotics used for wound care, alternative approaches are urgently required. In this study, α-aminophosphonate derivatives as antimicrobial agents were synthesized and incorporated into self-crosslinked tri-component cryogels composed of fully hydrolyzed polyvinyl alcohol (PVA-F), partially hydrolyzed polyvinyl alcohol (PVA-P), and cellulose nanofibrils (CNFs). Initially, the antimicrobial activity of four α-aminophosphonate derivatives against selected skin bacterial species was tested and their minimum inhibitory concentration was determined based on which the most effective compound was loaded into the cryogels. Next, the physical and mechanical properties of cryogels with various blending ratios of PVA-P/PVA-F and fixed amounts of CNFs were assessed, and drug release profiles and biological activities of drug-loaded cryogels were analyzed. Assessment of α-aminophosphonate derivatives showed the highest efficacy of a cinnamaldehyde-based derivative (Cinnam) against both Gram-negative and Gram-positive bacteria compared to other derivatives. The physical and mechanical properties of cryogels showed that PVA-P/PVA-F with a 50/50 blending ratio had the highest swelling ratio (1600%), surface area (523 m g), and compression recoverability (72%) compared to that with other blending ratios. Finally, antimicrobial and biofilm development studies showed that the cryogel loaded with a Cinnam amount of 2 mg (relative to polymer weight) showed the most sustained drug release profile over 75 h and had the highest efficacy against Gram-negative and Gram-positive bacteria. In conclusion, self-crosslinked tri-component cryogels loaded with the synthesized α-aminophosphonate derivative, having both antimicrobial and anti-biofilm formation properties, can have a significant impact on the management of uprising wound infection.
微生物感染是伤口愈合过程中最常见的障碍，导致伤口愈合受损和并发症，最终增加发病率和死亡率。由于用于伤口护理的现有抗生素的病原体耐药性不断增加，因此迫切需要替代方法。在这项研究中，合成了作为抗菌剂的α-氨基膦酸衍生物，并将其掺入由完全水解的聚乙烯醇（PVA-F）、部分水解的聚乙烯醇（PVA-P）和纤维素纳米纤维（CNFs）组成的自交联三组分冷冻凝胶中。首先，测试了四种α-氨基膦酸衍生物对选定皮肤细菌物种的抗菌活性，并根据其最小抑菌浓度确定了最有效的化合物被载入冷冻凝胶。接下来，评估了具有不同 PVA-P/PVA-F 混合比和固定 CNFs 量的冷冻凝胶的物理和机械性能，并分析了载药冷冻凝胶的药物释放曲线和生物活性。对α-氨基膦酸衍生物的评估表明，与其他衍生物相比，基于肉桂醛的衍生物（Cinnam）对革兰氏阴性和革兰氏阳性菌具有最高的功效。冷冻凝胶的物理和机械性能表明，与其他混合比相比，PVA-P/PVA-F 的 50/50 混合比具有最高的溶胀率（1600%）、比表面积（523 m g）和压缩恢复率（72%）。最后，抗菌和生物膜发展研究表明，载有 2 mg Cinnam（相对于聚合物重量）的冷冻凝胶在 75 h 内表现出最持续的药物释放曲线，对革兰氏阴性和革兰氏阳性菌具有最高的功效。总之，负载合成的α-氨基膦酸衍生物的自交联三组分冷冻凝胶具有抗菌和抗生物膜形成特性，可能对管理日益严重的伤口感染产生重大影响。
