Chen Chun-Han, Chang Cheng-Chih, Shih Tsung-Hsien, Aljuffali Ibrahim A, Yeh Ta-Sen, Fang Jia-You
Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan ; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Int J Nanomedicine. 2015 Mar 25;10:2403-16. doi: 10.2147/IJN.S79522. eCollection 2015.
Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence imaging showed a deeper and broader penetration of Nile red, the fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400 solution. Histological examination showed that SNEDDS caused more minor inflammation at the gastrointestinal membrane as compared with that caused by PEG 400 solution, indicating a shielding of direct silymarin contact with the mucosa by the nanodroplets. SNEDDS generally showed low-level or negligible irritation in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully developed to improve the dissolution, permeability, and oral bioavailability of silymarin. To the best of our knowledge, this is the first investigation reporting the usefulness of SNEDDS for improving drug malabsorption elicited by gastric bypass surgery.
Roux-en-Y胃旁路术（RYGB）是一种用于减轻肥胖患者体重的常见手术。尽管RYGB会限制食物摄入，但药物吸收也会减少。本研究的目的是开发新型自纳米乳化药物递送系统（SNEDDS），以增强水溶解度差的水飞蓟素的口服递送。通过粒径、zeta电位、液滴数量和形态对SNEDDS进行表征。在Sprague-Dawley大鼠身上进行了RYGB手术。在正常大鼠和RYGB大鼠中，以600mg/kg的水飞蓟素剂量给予SNEDDS，与水飞蓟素水悬浮液和聚乙二醇（PEG）400溶液进行比较。选择水飞蓟素的主要活性成分血浆水飞蓟宾来估算药代动力学参数。在模拟胃液中稀释的SNEDDS呈现出190nm的液滴尺寸，呈球形。与悬浮液和PEG 400溶液相比，纳米载体通过口服摄入使RYGB大鼠体内的水飞蓟宾利用率分别提高了2.5倍和1.5倍。接受SNEDDS的RYGB大鼠检测到水飞蓟宾有明显的双峰浓度。荧光成像显示，荧光染料尼罗红从SNEDDS进入胃肠道黏膜的深度和广度比从PEG 400溶液中更深更广。组织学检查表明，与PEG 400溶液相比，SNEDDS在胃肠道膜上引起的炎症更小，这表明纳米液滴屏蔽了水飞蓟素与黏膜的直接接触。SNEDDS在胃肠道中通常表现出低水平或可忽略不计的刺激性。成功开发了载水飞蓟素的SNEDDS，以改善水飞蓟素的溶解、渗透和口服生物利用度。据我们所知，这是首次报道SNEDDS对改善胃旁路手术引起的药物吸收不良有用性的研究。
