title: Pharmacokinetic and pharmacodynamic study of a phospholipid-based phase separation gel for once a month administration of octreotide.
abstract: 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 30days 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.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Mengxin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Shan
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China. Electronic address: yfu4@scu.edu.cn.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China. Electronic address: gongtaoy@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004285:Dogs; D004334:Drug Administration Schedule; D065546:Drug Liberation; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry; D007279:Injections, Subcutaneous; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D015282:Octreotide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D010743:Phospholipids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011817:Rabbits; D017207:Rats, Sprague-Dawley
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D005782:Gels; D010743:Phospholipids; D015282:Octreotide
keywords: Hepatocellular carcinoma; In situ gel; Octreotide; Pharmacokinetics; Phospholipid; Sustained release