微流控制备万古霉素负载PLGA微球治疗骨科感染的体外表征及体内性能

IF 2.1 3区 医学 Q2 ORTHOPEDICS
Dinesh Dhamecha, Mehmet D. Asik, Cecilia Nepple, Yingfang Fan, Amita Sekar, Keita Fujino, Fawaz Malick, Madeline McCanne, Ebru Oral, Orhun Muratoglu
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引用次数: 0

摘要

假体周围关节感染(PJI)是全关节置换术(TJA)的严重并发症,导致高翻修手术率、长期发病率和死亡率。传统的抗生素治疗往往存在有限的生物利用度和全身毒性。本研究探索了一种利用万古霉素负载聚乳酸-羟基乙酸(PLGA)微颗粒(VMP)的新方法,通过微流控双乳法配制,用于控制局部给药,以治疗PJI。合成的PLGA微粒具有高负载能力和持续的万古霉素释放,旨在维持治疗性关节内浓度。体外表征显示出最佳的负载能力(高达28% w/w),形貌均匀的粒径分布(49-65µm),并在8周内持续释放。使用大鼠关节感染模型评估体内疗效,显示与对照组相比,细菌活力显著降低,骨愈合增强。负重恢复评估显示,vmp治疗的大鼠功能恢复明显早于对照组(p
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In Vitro Characterization and In Vivo Performance of Vancomycin-Loaded PLGA Microspheres Prepared by Using Microfluidics for the Management of Orthopedic Infections

Periprosthetic joint infection (PJI) is a severe complication of total joint arthroplasty (TJA), leading to high rates of revision surgeries, long-term morbidity, and mortality. Conventional antibiotic treatments often suffer from limited bioavailability and systemic toxicity. This study explores a novel approach using vancomycin-loaded poly(lactic-co-glycolic) acid (PLGA) microparticles (VMP) formulated via a microfluidic double emulsion method for controlled, localized drug delivery for managing PJI. The PLGA microparticles were synthesized to achieve high loading capacity and sustained vancomycin release, aiming to maintain therapeutic intra-articular concentrations. In vitro characterization demonstrated optimal loading capacity (up to 28% w/w), morphology with a homogeneous particle size distribution (49–65 µm), and sustained release profiles over 8 weeks. In vivo efficacy was evaluated using a rat joint infection model, showing significant reductions in bacterial viability and enhanced bone healing compared to controls. Weight-bearing recovery assessments showed that VMP-treated rats regained functionality significantly earlier than controls (p < 0.05). Radiographic, histological, and immunofluorescent analyses confirmed reduced inflammation and improved bone integrity with VMP treatment. These findings suggest that microfluidic-synthesized PLGA microparticles provide a promising strategy for localized, controlled release of antibiotics, potentially helping the management of PJI and improving postsurgical outcomes. Future research should explore the long-term effects and scalability of clinical applications. This study lays the foundation for advancing controlled release systems in orthopedic postoperative care.

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来源期刊
Journal of Orthopaedic Research®
Journal of Orthopaedic Research® 医学-整形外科
CiteScore
6.10
自引率
3.60%
发文量
261
审稿时长
3-6 weeks
期刊介绍: The Journal of Orthopaedic Research is the forum for the rapid publication of high quality reports of new information on the full spectrum of orthopaedic research, including life sciences, engineering, translational, and clinical studies.
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