Liu Jingying, Christophersen Philip C, Yang Mingshi, Nielsen Hanne M, Mu Huiling
a Department of Pharmacy, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
b Wuya College of Innovation , Shenyang Pharmaceutical University , Shenyang , China.
Drug Dev Ind Pharm. 2017 Dec;43(12):2032-2042. doi: 10.1080/03639045.2017.1361967. Epub 2017 Aug 11.
The present study aimed at elucidating the influence of polymorphic stability of lipid excipients on the physicochemical characters of different solid lipid microparticles (SLM), with the focus on the alteration of protein distribution in SLM.
Labeled lysozyme was incorporated into SLM prepared with different excipients, i.e. trimyristin (TG14), glyceryl distearate (GDS), and glyceryl monostearate (GMS), by water-oil-water (w/o/w) or solid-oil-water (s/o/w) method. The distribution of lysozyme in SLM and the release of the protein from SLM were evaluated by confocal laser scanning microscopy. The storage stability of SLM was characterized by HPLC, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy.
Lysozyme was displayed as small scattered domains inside GDS and GMS SLM, whereas it was incorporated in the core of TG14 SLM formulated by the w/o/w method or evenly distributed in TG14 SLM prepared by the s/o/w method. Stability study at 37 °C revealed that only TG14 SLM made by the w/o/w method was able to maintain the lysozyme amount both on the particle surface and released from the SLM. Elevated storage temperature induced polymorphic transition of lipids in GDS and GMS SLM, which was, however, not remarkable for the TG14 SLM.
Lipid excipients and particle preparation methods were found to differently affect the lysozyme distribution in SLM, owning to varied storage stabilities of the lipids. The present study provides updated knowledge for rational development of lipid-based formulations for oral delivery of peptide or protein drugs.
本研究旨在阐明脂质辅料的多晶型稳定性对不同固体脂质微粒（SLM）物理化学性质的影响，重点关注SLM中蛋白质分布的变化。
通过水包油包水（w/o/w）或固体包油包水（s/o/w）方法，将标记的溶菌酶掺入用不同辅料（即肉豆蔻酸甘油酯（TG14）、二硬脂酸甘油酯（GDS）和单硬脂酸甘油酯（GMS））制备的SLM中。通过共聚焦激光扫描显微镜评估溶菌酶在SLM中的分布以及蛋白质从SLM中的释放。通过高效液相色谱、差示扫描量热法、X射线粉末衍射和扫描电子显微镜对SLM的储存稳定性进行表征。
溶菌酶在GDS和GMS SLM中表现为小的分散区域，而在通过w/o/w方法制备的TG14 SLM核心中掺入，或在通过s/o/w方法制备的TG14 SLM中均匀分布。37°C的稳定性研究表明，只有通过w/o/w方法制备的TG14 SLM能够在颗粒表面和从SLM释放时都保持溶菌酶的量。储存温度升高会诱导GDS和GMS SLM中脂质的多晶型转变，然而，这对TG14 SLM并不显著。
发现脂质辅料和颗粒制备方法对SLM中溶菌酶分布的影响不同，这归因于脂质储存稳定性的差异。本研究为合理开发用于口服递送肽或蛋白质药物的脂质制剂提供了最新知识。
