iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; School of Science and Health Technologies, University Lusófona, Campo Grande 376, 1749-024 Lisbon, Portugal.
iMed.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Mater Sci Eng C Mater Biol Appl. 2014 May 1;38:218-26. doi: 10.1016/j.msec.2014.02.002. Epub 2014 Feb 12.
Currently the safe and responsible use of antibiotics is a world-wide concern as it promotes prevention of the increasing emergence of multiresistant bacterial strains. Considering that there is a noticeable decline of the available antibiotic pipeline able to combat emerging resistance in serious infection a major concern grows around the prosthetic joint infections once the available commercial antibiotic loaded polymethylmethacrylate bone cements (BC) are inadequate for local antibiotic treatment, especially against MRSA, the most commonly isolated and antibiotic-resistant pathogen in bone infections. In this paper a novel modified BC matrix loaded with minocycline is proposed. A renewed interest in this tetracycline arises due to its broad-spectrum of activity against the main organisms responsible for prosthetic joint infections, especially against MRSA. The modified BC matrices were evaluated concerning minocycline release profile, biomechanical properties, solid-state characterization, antimicrobial stability and biocompatibility under in vitro conditions. BC matrix loaded with 2.5% (w/wBC) of minocycline and 10.0% (w/wBC) of lactose presented the best properties since it completely released the loaded minocycline, maintained the mechanical properties and the antimicrobial activity against representative strains of orthopedic infections. In vitro biocompatibility was assessed for the elected matrix and neither minocycline nor lactose loading enhanced BC cytotoxicity.
目前，安全、负责任地使用抗生素是全世界共同关注的问题，因为这有助于预防日益增多的多耐药菌的出现。鉴于能够对抗严重感染中出现的耐药性的现有抗生素药物研发管线明显减少，人们越来越关注人工关节感染，因为一旦现有的商业抗生素载聚甲基丙烯酸甲酯骨水泥（BC）不足以进行局部抗生素治疗，尤其是针对 MRSA，即骨骼感染中最常见的分离和耐药病原体，这种情况就会出现。在本文中，提出了一种新型的载有米诺环素的改良 BC 基质。由于其对引起人工关节感染的主要病原体具有广谱活性，尤其是对 MRSA 具有活性，因此人们对这种四环素重新产生了兴趣。改良的 BC 基质在载有米诺环素的释放曲线、生物力学性能、固态特性、抗菌稳定性和体外条件下的生物相容性方面进行了评估。载有 2.5%（w/wBC）米诺环素和 10.0%（w/wBC）乳糖的 BC 基质具有最佳性能，因为它完全释放了载有的米诺环素，保持了机械性能和对骨科感染代表性菌株的抗菌活性。对选定的基质进行了体外细胞相容性评估，载米诺环素和乳糖均未增强 BC 的细胞毒性。
