Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
Int J Pharm. 2018 Oct 25;550(1-2):149-159. doi: 10.1016/j.ijpharm.2018.08.025. Epub 2018 Aug 17.
Stimuli-responsive nano-drug delivery systems can optimize antibiotic delivery to infection sites. Identifying novel lipids for pH responsive delivery to acidic conditions of infection sites will enhance the performance of nano-drug delivery systems. The aim of the present investigation was to synthesize and characterize a biosafe novel pH-responsive lipid for vancomycin delivery to acidic conditions of infection sites. A pH-responsive solid lipid, N-(2-morpholinoethyl) oleamide (NMEO) was synthesized and used to prepare vancomycin (VCM)-loaded solid lipid nanoparticles (VCM_NMEO SLNs). The particle size (PS), polydispersity index (PDI), zeta potential (ZP) and entrapment efficiency (EE) of the formulation were 302.8 ± 0.12 nm, 0.23 ± 0.03, -6.27 ± 0.017 mV and 81.18 ± 0.57% respectively. The study revealed that drug release and antibacterial activity were significantly greater at pH 6.0 than at pH 7.4, while the in silico studies exposed the molecular mechanisms for improved stability and drug release. Moreover, the reduction of MRSA load was 4.14 times greater (p < 0.05) in the skin of VCM_NMEO SLNs treated mice than that of bare VCM treated specimens. Thus, this study confirmed that NMEO can successfully be used to formulate pH-responsive SLNs with potential to enhance the treatment of bacterial infections.
刺激响应型纳米药物递送系统可以优化抗生素在感染部位的递送。鉴定用于 pH 响应递送至感染部位酸性条件的新型脂质，将提高纳米药物递送系统的性能。本研究旨在合成和表征一种用于万古霉素递送至感染部位酸性条件的新型 pH 响应生物安全脂质。合成了一种 pH 响应固体脂质，N-(2-吗啉乙基)油酰胺（NMEO），并用于制备载万古霉素（VCM）的固体脂质纳米粒（VCM_NMEO SLNs）。制剂的粒径（PS）、多分散指数（PDI）、Zeta 电位（ZP）和包封效率（EE）分别为 302.8 ± 0.12nm、0.23 ± 0.03、-6.27 ± 0.017mV 和 81.18 ± 0.57%。研究表明，在 pH 6.0 时药物释放和抗菌活性明显大于 pH 7.4，而计算机模拟研究揭示了提高稳定性和药物释放的分子机制。此外，载有 VCM_NMEO SLNs 的小鼠皮肤中 MRSA 载量减少了 4.14 倍（p<0.05），而未载药的 VCM 处理标本则减少了 4.14 倍。因此，本研究证实 NMEO 可成功用于制备 pH 响应性 SLNs，具有增强细菌感染治疗的潜力。
