Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; School of Pharmacy and Health Sciences, United States International University of Africa, Nairobi, Kenya.
J Pharm Sci. 2020 Aug;109(8):2594-2606. doi: 10.1016/j.xphs.2020.05.011. Epub 2020 May 27.
The aim of this study was to synthesize a novel biocompatible pH-responsive oleic acid-based dendritic lipid amphiphile (OLA-SPDA) which self-assembled into stable micelles (OLA-SPDA -micelles) with a relatively low critical micelle concentration (CMC) of 5.6 × 10 M. The formulated micelles had particle size, polydispersity index (PDI) and zeta potential (ZP) of 84.16 ± 0.184 nm, 0.199 ± 0.011 and -42.6 ± 1.98 mV, respectively, at pH 7.4. The vancomycin (VCM) encapsulation efficiency was 78.80 ± 3.26%. The micelles demonstrated pH-responsiveness with an increase in particle size to 141.1 ± 0.0707 nm and a much faster release profile at pH 6.0, as compared to pH 7.4. The minimum inhibitory concentration (MIC) of VCM-OLA-SPDA-micelle against methicillin-resistant staphylococcus aureus (MRSA) was 8-fold lower compared to bare VCM, and the formulation had a 4-fold lower MIC at pH 6.0 when compared to the formulation's MIC at pH 7.4. MRSA viability assay showed the micelles had a percentage killing of 93.39% when compared bare-VCM (58.21%) at the same MIC (0.98 μg/mL). In vivo mice (BALB/c) skin infection models showed an 8-fold reduction in MRSA burden after treatment with VCM-OLA-SPDA-micelles when compared with bare VCM. The above results suggest that pH-responsive VCM-OLA-SPDA-micelles has the potential to be an effective carrier to enhance therapeutic outcomes against infections characterised by low pH.
本研究旨在合成一种新型的生物相容的 pH 响应油酸基树枝状脂质两亲物（OLA-SPDA），它可以自组装成具有相对较低临界胶束浓度（CMC）为 5.6×10 -5 M 的稳定胶束（OLA-SPDA-胶束）。在 pH 7.4 时，所形成的胶束的粒径、多分散指数（PDI）和 Zeta 电位（ZP）分别为 84.16±0.184nm、0.199±0.011 和-42.6±1.98mV。万古霉素（VCM）包封效率为 78.80±3.26%。与 pH 7.4 相比，胶束在 pH 6.0 时表现出 pH 响应性，粒径增加到 141.1±0.0707nm，释放速度更快。与裸 VCM 相比，VCM-OLA-SPDA-胶束对耐甲氧西林金黄色葡萄球菌（MRSA）的最低抑菌浓度（MIC）降低了 8 倍，当制剂在 pH 6.0 时的 MIC 与在 pH 7.4 时的 MIC 相比降低了 4 倍。MRSA 活力测定表明，在相同 MIC（0.98μg/mL）下，胶束的杀灭率为 93.39%，而裸 VCM 为 58.21%。体内（BALB/c）小鼠皮肤感染模型显示，与裸 VCM 相比，VCM-OLA-SPDA-胶束治疗后 MRSA 负荷减少了 8 倍。上述结果表明，pH 响应性 VCM-OLA-SPDA-胶束具有成为有效载体的潜力，可增强对低 pH 特征感染的治疗效果。
