Pharmacokinetic and pharmacodynamic study of a phospholipid-based phase separation gel for once a month administration of octreotide

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• 作者：Mengxin Wang ; Fengying Shan ; Yang Zou ; Xun Sun ; Zhi-Rong Zhang ; Yao Fu ; ^{yfu4@scu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Tao Gong ; ^{gongtaoy@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Octreotide ; Phospholipid ; In situ gel ; Sustained release ; Pharmacokinetics ; Hepatocellular carcinoma
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 May 2016
• 年：2016
• 卷：230
• 期：Complete
• 页码：45-56
• 全文大小：1716 K

文摘

As a natural somatostatin analog, octreotide acetate (OCT) has been extensively used in cancer treatment and growth hormone related diseases. The clinical application of OCT, however, is greatly limited by its short half-life, rapid elimination and clearance in vivo. In the current study, a high content phospholipid-based phase separation gel platform (PPSG) was presented, which could be injected in the soluble state and underwent rapid phase-separation into a gel-like implant after a single subcutaneous injection. OCT was dispersed homogeneously in the PPSG pre-gel solution to afford OCT-loaded PPSG (OCT-PPSG) after a single subcutaneous injection, which displayed controlled and sustained release profiles for up to 30 days in rats, rabbits and Beagle dogs. OCT-PPSG showed a less significant burst phase followed by a steady plasma concentration of OCT compared with Sandostatin^® (LAR) in Beagle dogs. Moreover, OCT-PPSG was demonstrated to show remarkable antitumor efficacy in both a primary rat model and a xenograft mouse model of hepatocellular carcinoma (HCC). PPSG thus represented a promising and viable in situ forming gel platform material for the long-term sustained release of peptides and protein drugs.