a Faculty of Pharmaceutical Sciences , Chulalongkorn University , Pathumwan , Bangkok , Thailand.
b Faculty of Pharmaceutical Sciences , University of Iceland , Reykjavik , Iceland.
Drug Dev Ind Pharm. 2019 Apr;45(4):560-567. doi: 10.1080/03639045.2019.1569023. Epub 2019 Jan 25.
Amphotericin B (AmB) is one of the most effective systemic antifungal agents, but its use is circumscribed by the dose-limiting toxicity of the conventional micellar dispersion formulation, Fungizone. Significantly lesser toxicity is obtained when AmB incorporated into the aqueous dispersion of lipid nanoparticles. The aim of this study was to develop and characterize AmB loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). NLC differed from SLN by the presence of liquid lipid, glyceryl tri(caprylate/caprate) in the lipid matrix. Various surfactants i.e. tween 20, cremophor RH40, poloxamer 407 (P407) and Myrj 52 were used to stabilize SLN and NLC. The effect of phospholipid incorporated in those lipid dispersions was also determined. Among surfactants tested, only P407 could stabilize AmB lipid dispersions. There was no chemical reaction occurred between AmB and other components that confirmed by Fourier transform infrared spectroscopy (FT-IR) spectra. The differential scanning calorimetry (DSC), hot-stage microscopy (HSM), powder X-ray diffractometry (PXRD) data showed that AmB was molecularly dispersed or in amorphous form in the lipid matrix. The proton nuclear magnetic resonance (H-NMR) results showed that in the presence of phospholipid oil clusters within the lipid matrix are formed. These results indicate that SLN and NLC stabilized by P407 and/or phospholipid as the colloidal carrier for AmB were successfully developed.
两性霉素 B（AmB）是最有效的系统抗真菌药物之一，但由于常规胶束分散制剂（Fungizone）的剂量限制毒性，其应用受到限制。当两性霉素 B 被包裹在脂质纳米粒的水性分散体中时，可获得显著较少的毒性。本研究旨在开发和表征两性霉素 B 负载的固体脂质纳米粒（SLN）和纳米结构脂质载体（NLC）。NLC 与 SLN 的区别在于脂质基质中存在液体脂质，即甘油三（辛酸/癸酸）。各种表面活性剂，如吐温 20、吐温 40 聚氧乙烯醚（RH40）、泊洛沙姆 407（P407）和 Myrj 52，用于稳定 SLN 和 NLC。还确定了在这些脂质分散体中加入磷脂的效果。在所测试的表面活性剂中，只有 P407 可以稳定两性霉素 B 脂质分散体。傅立叶变换红外光谱（FT-IR）谱证实，两性霉素 B 与其他成分之间没有发生化学反应。差示扫描量热法（DSC）、热台显微镜（HSM）、粉末 X 射线衍射（PXRD）数据表明，两性霉素 B 以分子形式分散或呈无定形形式存在于脂质基质中。质子核磁共振（H-NMR）结果表明，在磷脂存在下，脂质基质内形成了油簇。这些结果表明，由 P407 和/或磷脂稳定的 SLN 和 NLC 作为两性霉素 B 的胶体载体已成功开发。
