Multi-layer polymeric implants for sustained release of chemopreventives.
Multi-layer polymeric implants for sustained release of chemopreventives.
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DOI：
10.1016/j.canlet.2012.07.017
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发表时间：
2012-12-29
期刊：
影响因子：
9.7
通讯作者：
Gupta, Ramesh C.
中科院分区：
文献类型：
--
作者：
Aqil, Farrukh;Jeyabalan, Jeyaprakash;Kausar, Hina;Bansal, Shyam S.;Sharma, Ram J.;Singh, Inder P.;Vadhanam, Manicka V.;Gupta, Ramesh C.
关键词：
口服生物利用度差限制了许多化学预防剂在预防和治疗癌症中的使用。为了克服这一限制，我们报告了一种使用姜黄素、单独的姜黄素、醉茄素A和奥替普拉的简易植入物制剂（“包衣”植入物）。该方法包括用20-30层10-20%聚己内酯二氯甲烷溶液（含0.5-2%试验试剂）涂覆空白聚己内酯植入物。体外释放表明，虽然奥替普拉在8周内几乎以零级动力学释放，但姜黄素、单独的姜黄素和醉茄素A以一些初始爆发释放。通过在A/J小鼠中皮下移植植入物来测定体内释放。当通过包衣植入物递送时，与假处理相比，用二苯并[a，l]芘处理的小鼠中的奥替普拉显著减少肺DNA加合物（28±7对54±17加合物/109个核苷酸）。Withaferin A也减少DNA加合物，但不显著。姜黄素和单独的姜黄素类化合物无效。通过UPLC-荧光分析肺、肝和脑显示存在三种测试类姜黄素，表明植入物递送系统的有效性。此外，基于其已知的体内抗肿瘤活性，通过植入物给予的醉茄素A显著抑制了无胸腺裸鼠中的人肺癌A549异种移植物，而当腹膜内给予相同的总剂量时，它无效，并且需要超过2倍的高剂量才能产生有效性。总之，我们的数据表明，涂层聚合物植入物可以容纳热不稳定的化合物，可以提供长期持续释放，并引发DNA损伤抑制和抗肿瘤活性。
Poor oral bioavailability limits the use of many chemopreventives in the prevention and treatment of cancer. To overcome this limitation, we report an improvised implant formulation (“coated” implants) using curcumin, individual curcuminoids, withaferin A and oltipraz. This method involves the coating of blank polycaprolactone implants with 20–30 layers of 10–20% polycaprolactone solution in dichloromethane containing 0.5–2% of the test agent. The in vitro release showed that while oltipraz was released with almost zero-order kinetics over eight weeks, curcumin, individual curcuminoids and withaferin A were released with some initial burst. The in vivo release was determined by grafting implants subcutaneously in A/J mice. When delivered by coated implants, oltipraz significantly diminished lung DNA adducts in mice treated with dibenzo[a, l]pyrene compared with sham treatment (28±7 versus 54±17 adducts/109 nucleotides). Withaferin A also diminished DNA adducts, but it was insignificant. Curcumin and individual curcuminoids were ineffective. Analysis of lung, liver and brain by UPLC-fluorescence showed the presence of the three test curcuminoids indicating effectiveness of the implant delivery system. Further, based on its known antitumor activity in vivo, withaferin A given via the implants significantly inhibited human lung cancer A549 xenograft in athymic nude mice, while it was ineffective when the same total dose was administered i.p. and required over 2-fold higher dose to elicit effectiveness. Together, our data suggest that coated polymeric implants can accommodate heat-labile compounds, can furnish sustained release for long duration, and elicit DNA damage-inhibiting and anti-tumor activities.
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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：
11.2
作者：
Stan, Silvia D.;Hahm, Eun-Ryeong;Warin, Renaud;Singh, Shivendra V.
通讯作者：
Singh, Shivendra V.
影响因子：
14
作者：
Sun, HF;Mei, L;Wang, PY
通讯作者：
Wang, PY
影响因子：
4.7
作者：
Munagala, Radha;Kausar, Hina;Gupta, Ramesh C.
通讯作者：
Gupta, Ramesh C.
影响因子：
3.7
作者：
Bansal, Shyam S.;Vadhanam, Manicka V.;Gupta, Ramesh C.
通讯作者：
Gupta, Ramesh C.