Matos Ana C, Ribeiro Isabel A C, Guedes Rita C, Pinto Rosana, Vaz Mário A, Gonçalves Lídia M, Almeida António J, Bettencourt Ana F
Research Institute for Medicines (iMed. ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisbon, Portugal.
INEGI, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n 4200-465 Porto, Portugal.
Int J Pharm. 2015 May 15;485(1-2):317-28. doi: 10.1016/j.ijpharm.2015.03.035. Epub 2015 Mar 19.
Antibiotic-loaded acrylic bone cements (ALABCs) are widely used to decrease the occurrence of bone infections in cemented arthroplasties and actually being considered as a more cost-effective procedure when compared to cementless implants. However, ALABCs have a major drawback, which is the incomplete release of the antibiotics and, as a result, pathogens that commonly are responsible for those infections are becoming resistant. Consequently, it is of most relevance to find new antibacterial agents to load into BC with an effective mechanism against those microorganisms. This research work intended to load levofloxacin, a fluoroquinolone with anti-staphylococcal activity and adequate penetration into osteoarticular tissues, on lactose-modified commercial bone cement (BC). This modified BC matrix exhibited increased levofloxacin release and delayed Staphylococcus aureus biofilm formation. Further insights on material-drug interaction during BC setting were investigated by density functional theory calculations. The obtained results suggested that favorable covalent and non-covalent interactions could be established between levofloxacin and the BC. Moreover, BC mechanical and biocompatibility properties were maintained. These features justify the potential of levofloxacin-loaded modified-BC as a valuable approach for local antibiotic delivery in bone infections management.
载抗生素丙烯酸骨水泥（ALABCs）被广泛用于降低骨水泥型关节置换术中骨感染的发生率，与非骨水泥型植入物相比，实际上被认为是一种更具成本效益的方法。然而，ALABCs有一个主要缺点，即抗生素释放不完全，结果，通常导致这些感染的病原体产生了耐药性。因此，寻找新的抗菌剂以有效机制加载到骨水泥中对抗这些微生物至关重要。本研究旨在将具有抗葡萄球菌活性且能充分渗透到骨关节组织中的氟喹诺酮类药物左氧氟沙星加载到乳糖改性的商用骨水泥（BC）上。这种改性的BC基质表现出左氧氟沙星释放增加和金黄色葡萄球菌生物膜形成延迟。通过密度泛函理论计算对骨水泥凝固过程中材料与药物的相互作用进行了进一步研究。所得结果表明，左氧氟沙星与骨水泥之间可以建立良好的共价和非共价相互作用。此外，可以保持骨水泥的机械性能和生物相容性。这些特性证明了载左氧氟沙星改性骨水泥作为骨感染治疗中局部抗生素递送的一种有价值方法的潜力。
