Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China; School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
J Control Release. 2023 Dec;364:393-405. doi: 10.1016/j.jconrel.2023.10.040. Epub 2023 Nov 3.
The development of potent bactericidal antibiotic alternatives is important to address the current antibiotic crisis. A representative example is the topical delivery of predatory Bdellovibrio bacteriovorus bacteria to treat ocular bacterial infection. However, the direct topical use of B. bacteriovorus suspensions has the problem of easy loss and inactivation. Here, a B. bacteriovorus in situ forming hydrogel (BIG) was constructed for the ocular delivery of B. bacteriovorus. BIGs, as a fluid in their primitive state, were temperature- and cation- dually sensitive, which was rapidly transformed into immobile gels in the ocular environment. BIGs not only kept the activity of B. bacteriovorus but also retained on the ocular surface for a long time. The biosafety of BIGs was good without HCEC cell toxicity and hemolysis. More importantly, BIGs highly inhibited the growth of drug-resistant Pseudomonas aeruginosa whether in vitro or in the infected rat eyes. The ocular infection was completely controlled by BIGs with no corneal ulcers and inflammations. This living bacteria gel is a promising medication for the local treatment of drug-resistant bacteria-induced ocular infection.
开发高效杀菌抗生素替代品对于应对当前的抗生素危机至关重要。一个代表性的例子是利用捕食性蛭弧菌（Bdellovibrio bacteriovorus）局部递送来治疗眼部细菌感染。然而，直接将 B. bacteriovorus 悬浮液用于局部治疗存在易失活和易失活的问题。本研究构建了一种用于眼部递呈 B. bacteriovorus 的原位形成水凝胶（BIG）。BIG 作为原始状态的流体，对温度和阳离子具有双重敏感性，在眼部环境中迅速转化为不可移动的凝胶。BIG 不仅保持了 B. bacteriovorus 的活性，而且还能长时间保留在眼部表面。BIG 具有良好的生物安全性，对人角膜上皮细胞（HCEC）没有细胞毒性和溶血作用。更重要的是，BIG 高度抑制了耐药铜绿假单胞菌的生长，无论是在体外还是在感染大鼠眼睛中。BIG 完全控制了眼部感染，没有角膜溃疡和炎症。这种活菌凝胶有望成为局部治疗耐药菌引起的眼部感染的药物。
