Argenziano Monica, Banche Giuliana, Luganini Anna, Finesso Nicole, Allizond Valeria, Gulino Giulia Rossana, Khadjavi Amina, Spagnolo Rita, Tullio Vivian, Giribaldi Giuliana, Guiot Caterina, Cuffini Anna Maria, Prato Mauro, Cavalli Roberta
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via P. Giuria 9, 10125 Torino, Italy.
Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Via Santena 9, 10126 Torino, Italy.
Int J Pharm. 2017 May 15;523(1):176-188. doi: 10.1016/j.ijpharm.2017.03.033. Epub 2017 Mar 19.
Vancomycin (Vm) currently represents the gold standard against methicillin-resistant Staphylococcus aureus (MRSA) infections. However, it is associated with low oral bioavailability, formulation stability issues, and severe side effects upon systemic administration. These drawbacks could be overcome by Vm topical administration if properly encapsulated in a nanocarrier. Intriguingly, nanobubbles (NBs) are responsive to physical external stimuli such as ultrasound (US), promoting drug delivery. In this work, perfluoropentane (PFP)-cored NBs were loaded with Vm by coupling to the outer dextran sulfate shell. Vm-loaded NBs (VmLNBs) displayed ∼300nm sizes, anionic surfaces and good drug encapsulation efficiency. In vitro, VmLNBs showed prolonged drug release kinetics, not accompanied by cytotoxicity on human keratinocytes. Interestingly, VmLNBs were generally more effective than Vm alone in MRSA killing, with VmLNB antibacterial activity being more sustained over time as a result of prolonged drug release profile. Besides, VmLNBs were not internalized by staphylococci, opposite to Vm solution. Further US association promoted drug delivery from VmLNBs through an in vitro model of porcine skin. Taken together, these results support the hypothesis that proper Vm encapsulation in US-responsive NBs might be a promising strategy for the topical treatment of MRSA wound infections.
万古霉素（Vm）目前是治疗耐甲氧西林金黄色葡萄球菌（MRSA）感染的金标准。然而，它存在口服生物利用度低、制剂稳定性问题以及全身给药时的严重副作用。如果将Vm正确封装在纳米载体中，通过局部给药可以克服这些缺点。有趣的是，纳米气泡（NBs）对超声（US）等物理外部刺激有反应，可促进药物递送。在这项工作中，通过与外部硫酸葡聚糖壳偶联，将全氟戊烷（PFP）为核心的NBs负载上Vm。负载Vm的NBs（VmLNBs）尺寸约为300nm，表面带负电荷，且药物包封效率良好。在体外，VmLNBs显示出延长的药物释放动力学，对人角质形成细胞无细胞毒性。有趣的是，在杀灭MRSA方面，VmLNBs通常比单独的Vm更有效，由于药物释放曲线延长，VmLNB的抗菌活性随时间更持久。此外，与Vm溶液相反，葡萄球菌不会摄取VmLNBs。进一步的超声联合通过猪皮肤体外模型促进了VmLNBs的药物递送。综上所述，这些结果支持这样一种假设，即将Vm正确封装在对超声响应的NBs中可能是局部治疗MRSA伤口感染的一种有前景的策略。
