Ji Hongyu, Tang Jingling, Li Mengting, Ren Jinmei, Zheng Nannan, Wu Linhua
a Department of Pharmacy, the Second Affiliated Hospital, Harbin Medical University , Key Laboratory of Medications Research, College of Heilongjiang Province , Harbin , P. R. China and.
b Department of Pharmaceutics, School of Pharmacy , Harbin Medical University , Harbin , P. R. China.
Drug Deliv. 2016;23(2):459-70. doi: 10.3109/10717544.2014.918677. Epub 2014 Jun 3.
The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin.
The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin.
The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p < 0.01). The in situ intestinal absorption study revealed that the effective permeability (Peff) value of curcumin for SLNs was significantly improved (p < 0.01) comparing to curcumin solution.
Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.
本研究旨在用P-糖蛋白调节剂辅料TPGS和Brij78制备姜黄素固体脂质纳米粒（Cur-SLNs），以提高姜黄素的溶解度和生物利用度。
通过Plackett-Burman筛选设计和Box-Behnken实验设计对制剂进行优化。然后对Cur-SLNs的理化性质、包封率和体外释放进行表征。进行体内药代动力学研究和原位单通道肠道灌注，以研究Cur-SLNs对姜黄素生物利用度和肠道吸收的影响。
优化后的制剂平均粒径为135.3±1.5nm，ζ电位值为-24.7±2.1mV，药物包封率为91.09%±1.23%，同时呈现出缓释特性。体内药代动力学研究表明，Cur-SLNs的AUC0→t比姜黄素混悬液大12.27倍，Cur-SLNs的相对生物利用度为942.53%。同时，与混悬液相比，Cur-SLNs中姜黄素的Tmax和t(1/2)均延迟（p<0.01）。原位肠道吸收研究表明，与姜黄素溶液相比，姜黄素在SLNs中的有效渗透率（Peff）值显著提高（p<0.01）。
含有TPGS和Brij78的Cur-SLNs可有效提高姜黄素的口服生物利用度和肠道吸收。
