Co-delivery of natural metabolic inhibitors in a self-microemulsifying drug delivery system for improved oral bioavailability of curcumin.
Co-delivery of natural metabolic inhibitors in a self-microemulsifying drug delivery system for improved oral bioavailability of curcumin.
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DOI：
10.1007/s13346-014-0199-6
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发表时间：
2014-08
影响因子：
5.4
通讯作者：
Panyam, Jayanth
中科院分区：
文献类型：
--
作者：
Grill, Alex E.;Koniar, Brenda;Panyam, Jayanth
尽管姜黄素具有良好的抗癌化学预防和治疗活性，但其口服生物利用度差限制了其临床开发。姜黄素具有低水溶性，口服给药后经历广泛的首过代谢。我们假设姜黄素的口服生物利用度可以通过同时增加其吸收和降低其代谢清除率来提高。为了验证这一假设，我们制定了姜黄素与天然存在的UGT抑制剂（胡椒碱，槲皮素，柑橘苷，和水飞蓟宾）的自微乳化给药系统（SMEDDS）。小鼠肝微粒体研究表明，水飞蓟宾和槲皮素有效地抑制姜黄素葡萄糖醛酸化。当小鼠口服给药时，仅含姜黄素的SMEDDS增加了血浆中姜黄素葡萄糖醛酸苷的浓度，而不显著影响母体药物浓度。在体内检测的四种抑制剂中，水飞蓟宾显著提高了姜黄素的Cmax（0.15 μM vs. 0.03 μM姜黄素SMEDDS）和总体生物利用度（3.5倍vs.姜黄素SMEDDS）。先前的研究表明，水飞蓟宾也具有抗癌活性。因此，水飞蓟宾与姜黄素在SMEDDS中的共递送代表了改善姜黄素生物利用度的新颖且有前途的方法。
In spite of its well-documented anticancer chemopreventive and therapeutic activity, the clinical development of curcumin has been limited by its poor oral bioavailability. Curcumin has low aqueous solubility and undergoes extensive first pass metabolism following oral dosing. We hypothesized that oral bioavailability of curcumin can be enhanced by increasing its absorption and decreasing its metabolic clearance simultaneously. To test this hypothesis, we formulated curcumin with naturally occurring UGT inhibitors (piperine, quercetin, tangeretin, and silibinin) in a self-microemulsifying drug delivery system (SMEDDS). Mouse liver microsome studies showed that silibinin and quercetin inhibited curcumin glucuronidation effectively. When dosed orally in mice, the SMEDDS containing curcumin alone increased curcumin glucuronide concentrations in plasma without significantly affecting parent drug concentration. Of the four inhibitors examined in vivo, silibinin significantly improved the Cmax (0.15 μM vs. 0.03 μM for curcumin SMEDDS) and the overall bioavailability (3.5-fold vs. curcumin SMEDDS) of curcumin. Previous studies have shown that silibinin has anticancer activity as well. Thus, co-delivery of silibinin with curcumin in SMEDDS represents a novel and promising approach to improve curcumin bioavailability.
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DOI：
10.1158/1940-6207.capr-10-0006
发表时间：
2011-08
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Bansal SS;Goel M;Aqil F;Vadhanam MV;Gupta RC
通讯作者：
Gupta RC
影响因子：
3.8
作者：
Kakarala, Madhuri;Brenner, Dean E.;Korkaya, Hasan;Cheng, Connie;Tazi, Karim;Ginestier, Christophe;Liu, Suling;Dontu, Gabriela;Wicha, Max S.
通讯作者：
Wicha, Max S.
影响因子：
3.7
作者：
Deep G;Gangar SC;Rajamanickam S;Raina K;Gu M;Agarwal C;Oberlies NH;Agarwal R
通讯作者：
Agarwal R
影响因子：
5.8
作者：
Cui, Jing;Yu, Bo;Zhai, Guangxi
通讯作者：
Zhai, Guangxi
影响因子：
7.9
作者：
Khajuria, A;Thusu, N;Zutshi, U
通讯作者：
Zutshi, U