Lee Jeong-Jun, Park Ju-Hwan, Lee Jae-Young, Jeong Jae Young, Lee Song Yi, Yoon In-Soo, Kang Wie-Soo, Kim Dae-Duk, Cho Hyun-Jong
College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Colloids Surf B Biointerfaces. 2016 Apr 1;140:239-245. doi: 10.1016/j.colsurfb.2015.12.047. Epub 2015 Dec 29.
Omega-3 (ω-3) fish oil-enriched colloidal systems were developed for the oral delivery of Angelica gigas Nakai (AGN) extract (ext). By constructing a pseudo-ternary phase diagram, the composition of oil-in-water (o/w) microemulsion (ME) systems based on ω-3 (oil), Labrasol (surfactant), and water was determined. AGN ext was dissolved into the ME system and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was added to the ME formulation in order to enhance the mucosal absorption of the pharmacologically active ingredients in the AGN ext. The droplet size of AGN-loaded MEs was 205-277 nm and their morphology was spherical. The release of major components of AGN, decursin (D) and decursinol angelate (DA), from ME formulations in pH 1.2 and 6.8 buffers was significantly greater (P<0.05) than that from the AGN suspension group. The pharmacokinetic properties of AGN-loaded MEs in rats were evaluated by measuring decursinol (DOH) concentrations in plasma after oral administration. TPGS-included ME (F2) resulted in significantly greater (P<0.05) systemic exposure of DOH than that with ME without TPGS (F1), AGN ext+TPGS, and AGN in suspension. Severe toxicity of F1 and F2 on the intestinal epithelium was not observed by histological staining. The colloidal carriers described herein are promising delivery systems for oral administration of AGN ext.
开发了富含ω-3鱼油的胶体系统用于当归提取物(AGN ext)的口服给药。通过构建伪三元相图,确定了基于ω-3(油)、Labrasol(表面活性剂)和水的水包油(o/w)微乳液(ME)系统的组成。将AGN ext溶解到ME系统中,并向ME制剂中添加d-α-生育酚聚乙二醇1000琥珀酸酯(TPGS),以增强AGN ext中药理活性成分的粘膜吸收。载有AGN的微乳液的液滴尺寸为205-277nm,形态为球形。在pH 1.2和6.8缓冲液中,ME制剂中AGN的主要成分紫花前胡素(D)和紫花前胡醇当归酸酯(DA)的释放量显著高于(P<0.05)AGN悬浮液组。通过测量口服给药后大鼠血浆中紫花前胡醇(DOH)的浓度,评估了载有AGN的微乳液的药代动力学特性。含TPGS的微乳液(F2)导致DOH的全身暴露量显著高于(P<0.05)不含TPGS的微乳液(F1)、AGN ext+TPGS和悬浮液中的AGN。组织学染色未观察到F1和F2对肠上皮的严重毒性。本文所述的胶体载体是用于口服AGN ext的有前景的给药系统。