中文摘要：水凝胶是一种很好的噬菌体载体，能保持伤口湿润，起到保护屏障的作用，促进伤口愈合。本研究旨在制备生物稳定的噬菌体水凝胶，实现感染性噬菌体的控释。在羟乙基纤维素(HEC)、羟丙基甲基纤维素(HPMC)、聚乙烯氧化物(PEO)、聚乙烯醇(PVA)、羟丙基纤维素(HPC)和聚乙烯吡咯烷酮(PVP)等非离子型聚合物水凝胶(10(9)PFU/g)中制备以假单胞菌为靶点的噬菌体：PEV1 (肌病毒)和PEV31 (短尾病毒)，并评估了制剂的物理性质、体外释放曲线、抗菌活性和储存稳定性。发现了7.5%PEO、20%PVA和75%PVP水凝胶中噬菌体的控释，在8h内PFU释放>10（8）。5%HPMC、5%HEC和30%HPC凝胶中的噬菌体释放较差（7x10（5）-4x10（7）PFU）。优化后的水凝胶具有噬菌体特异性，滴度损失PEV1（0-0.8 log）小于PEV31（0.3-1.4 log）。两种噬菌体在PEO、PVA和HPMC水凝胶中保持稳定，在5℃条件下保存，滴度降低<1 log。可见，7.5%PEO和20%PVA水凝胶制剂是前景很好的治疗系统，可用于递送噬菌体治疗伤口感染。
外文摘要：Hydrogel is an attractive delivery vehicle for phages as it keeps the wound moist, acts as a protective barrier and facilitates wound healing process. The aim of this study was to formulate biologically stable phage hydrogels that enable controlled release of infective phages. Pseudomonas-targeting phages, PEV1 (myovirus) and PEV31 (podovirus) were formulated in hydrogels (10(9) PFU/g) consisting of non-ionic polymers, including hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), polyethylene oxide (PEO), polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC) and polyvinylpyrrolidone (PVP). The formulations were evaluated for physical properties, in vitro release profiles, antibacterial activity, and storage stability. Controlled release of phages was observed in 7.5% PEO, 20% PVA and 75% PVP hydrogels with >10(8) PFU release within 8 h. Poor phage release (7 x 10(5)-4 x 10(7) PFU) was observed in 5% HPMC, 5% HEC and 30% HPC gels. The biostability of the optimized hydrogels was phage-specific with less titer loss observed for PEV1 (0-0.8 log) than for PEV31 (0.3-1.4 log). Both phages remained stable in PEO, PVA and HPMC hydrogels with <1 log titer reductions when stored at 5 degrees C. This study showed that 7.5% PEO and 20% PVA hydrogel formulations could be promising therapeutic systems for delivering phages for the treatment of wound infections.
外文关键词：Bacteriophage (phage) therapy；Formulation；Phage hydrogel；Pseudomonas aeruginosa；Topical treatment；Wound infections
作者：Chang, RYK；Okamoto, Y；Morales, S；Kutter, E；Chan, HK
作者单位：Univ Sydney；Sojo Univ；Phage Consulting；Evergreen State Coll
期刊名称：INTERNATIONAL JOURNAL OF PHARMACEUTICS
期刊影响因子：4.845
出版年份：2021
出版刊次：605
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