Dubashynskaya Natallia V, Skorik Yury A
Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoy pr. V.O. 31, St. Petersburg 199004, Russia.
Pharmaceuticals (Basel). 2020 Apr 29;13(5):83. doi: 10.3390/ph13050083.
Polymyxins are vital antibiotics for the treatment of multiresistant Gram-negative ESKAPE pathogen infections. However, their clinical value is limited by their high nephrotoxicity and neurotoxicity, as well as their poor permeability and absorption in the gastrointestinal tract. This review focuses on various polymyxin delivery systems that improve polymyxin bioavailability and reduce drug toxicity through targeted and controlled release. Currently, the most suitable systems for improving oral, inhalation, and parenteral polymyxin delivery are polymer particles, liposomes, and conjugates, while gels, polymer fibers, and membranes are attractive materials for topical administration of polymyxin for the treatment of infected wounds and burns. In general, the application of these systems protects polymyxin molecules from the negative effects of both physiological and pathological factors while achieving higher concentrations at the target site and reducing dosage and toxicity. Improving the properties of polymyxin will be of great interest to researchers who are focused on developing antimicrobial drugs that show increased efficacy and safety.
多粘菌素是治疗多重耐药革兰氏阴性ESKAPE病原体感染的重要抗生素。然而，它们的临床价值受到其高肾毒性和神经毒性以及在胃肠道中较差的渗透性和吸收性的限制。本综述重点关注各种多粘菌素递送系统，这些系统通过靶向和控释来提高多粘菌素的生物利用度并降低药物毒性。目前，用于改善口服、吸入和肠胃外多粘菌素递送的最合适系统是聚合物颗粒、脂质体和缀合物，而凝胶、聚合物纤维和膜是用于局部施用多粘菌素以治疗感染伤口和烧伤的有吸引力的材料。一般来说，这些系统的应用可保护多粘菌素分子免受生理和病理因素的负面影响，同时在靶位点达到更高浓度并降低剂量和毒性。改善多粘菌素的性能将引起专注于开发疗效和安全性更高的抗菌药物的研究人员的极大兴趣。
