Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran.
Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran.
Lett Appl Microbiol. 2024 Oct 1;77(10). doi: 10.1093/lambio/ovae092.
Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies.
生物膜介导的骨髓炎带来了重大的治疗挑战。鉴于现有骨髓炎治疗方法的局限性，因此非常有必要开发一种局部药物递送系统，该系统需要具有生物相容性、可生物降解性和能够控制抗生素释放的特性。多泡脂质体（MVLs）的特点是非同心泡囊结构、独特的组成和增强的稳定性，可作为一种强大的缓释药物递送平台的系统。在这项研究中，制备并评估了由泊洛沙姆 407 和其他水凝胶组成的各种水凝胶制剂，其中包含盐酸万古霉素（VAN HL）负载的 MVLs（VAN HL-MVLs）。由泊洛沙姆 407 和透明质酸组成的优化的 VAN HL-MVL 溶胶-凝胶系统成功地将药物释放维持长达 3 周，并在 37°C 下表现出剪切稀化行为。虽然单独的 MVL 中的药物完全释放发生在 312 h 内，但水凝胶制剂将这种释放延长到 504 h。释放的药物在 24 h 内有效抑制了金黄色葡萄球菌生物膜的生长，在 72 h 内抑制了耐甲氧西林金黄色葡萄球菌生物膜的生长。它还分别在 96 和 120 h 内消除了金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌的预形成生物膜。这种包含 VAN HL-MVL 的可注射原位凝胶系统作为骨髓炎治疗多次手术的替代方案具有潜力，值得进一步研究。
