Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Mater Sci Eng C Mater Biol Appl. 2020 Oct;115:110761. doi: 10.1016/j.msec.2020.110761. Epub 2020 Feb 19.
Knee joint infection following total knee arthroplasty (TKA) is a serious condition and the treatments are complicated. The intra-articular solvent exchange-induced in situ forming matrix is of interest for modulating the release of antibiotics with a high drug concentration and a long period of exposed time at the target site. Stearic acid (S) and lauric acid (L) at various ratios were used as matrix formers by dissolving them in biocompatible solvents such as N-methyl pyrrolidone (NMP) and dimethyl sulfoxide (DMSO). Their matrix formation behaviors in phosphate buffer (pH7.4) and hyaluronic acid (HA) solution were evaluated. Also, the density, viscosity, injectability, solvent diffusion, in vitro degradability and drug release using the dialysis tube method were investigated. The L:S ratio of 1:1 in DMSO exhibited rapid matrix formation and a remarkably low viscosity (7.67±0.03 cp) with acceptable injectability (0.608±0.027N and 0.867±0.010N through 18-G and 27-G, respectively). Vancomycin HCl (V)-loaded L/S in situ forming matrix still provided ease of injection (1.079±0.215N and 1.230±0.145N through 18-G and 27-G needle, respectively) with fatty acid matrix formation after solvent exchange within 1min, whilst V sustainably released over 6days. It also presented effective antimicrobial activities against standard Staphylococcus aureus and methicillin-resistant Staphylococcus aureus strains. Therefore, V-loaded solvent exchange-induced in situ forming matrix using L and S as the matrix formers may be a potential local delivery system for treating knee joint infections occurring after TKA in the future.
膝关节置换术后感染（TKA）是一种严重的疾病，治疗方法复杂。关节内溶剂交换诱导原位形成基质对于调节抗生素的释放具有重要意义，因为它可以在目标部位提供高药物浓度和长时间的暴露时间。使用硬脂酸（S）和月桂酸（L）以不同比例作为基质形成剂，将它们溶解在生物相容性溶剂中，如 N-甲基吡咯烷酮（NMP）和二甲基亚砜（DMSO）。评估了它们在磷酸盐缓冲液（pH7.4）和透明质酸（HA）溶液中的基质形成行为。此外，还研究了密度、粘度、可注射性、溶剂扩散、体外降解性和通过透析管法的药物释放。DMSO 中 1:1 的 L:S 比表现出快速的基质形成和极低的粘度（7.67±0.03cp），具有可接受的可注射性（分别通过 18-G 和 27-G 注射时的 0.608±0.027N 和 0.867±0.010N）。载万古霉素盐酸盐（V）的 L/S 原位形成基质在溶剂交换 1min 内形成脂肪酸基质后，仍可轻松注射（分别通过 18-G 和 27-G 针注射时的 1.079±0.215N 和 1.230±0.145N），且 V 可持续释放超过 6 天。它还对标准金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌菌株表现出有效的抗菌活性。因此，使用 L 和 S 作为基质形成剂的载 V 的溶剂交换诱导原位形成基质可能是未来治疗 TKA 后膝关节感染的潜在局部给药系统。
