title: Parenteral thermo-sensitive organogel for schizophrenia therapy, in vitro and in vivo evaluation.
abstract: Novel biodegradable in situ forming organogel, obtained via the self-assembly of long chain fatty acid in pharmaceutical oil, was prepared and characterized. Different from traditional organogels, the use of organic solvent was avoided in this gel system, in consideration of its tissue irritation. Four kinds of fatty acids were employed as organogelators, which could successfully gel with injectable soybean oil. The gelation procedure was thermo-reversible. Phase transition temperature and time were depended on carbon chain length and concentration of gelators. Optimized formulations containing drug were then injected subcutaneously in rats for pharmacokinetic study. Results showed the steady drug release for one week with the well-controlled burst, which fitted well with the drug release mechanism of both drug diffusion and frame erosion. In vivo imaging of the organogel with fluorescence in live animals suggested that the organogel matrix was gradually absorbed and completely up-taken in nine days. Histopathological analysis of the surrounding tissues was carried out and revealed an overall good biocompatibility property of the implants over drug release period. This research demonstrates that this thermo-sensitive in situ forming organogel system represents a potentially promising platform for sustained drug delivery.
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun, Jilin Province 130012, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun, Jilin Province 130012, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun, Jilin Province 130012, China.
authors.forename: Ximing
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun, Jilin Province 130012, China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun, Jilin Province 130012, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun, Jilin Province 130012, China; State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai 264000, China. Electronic address: tenglesheng@jlu.edu.cn.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun, Jilin Province 130012, China. Electronic address: liyouxin@jlu.edu.cn.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D003374:Coumarins / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005227:Fatty Acids / Q000737:chemistry; D005782:Gels; D007555:Isoxazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008819:Mice, Nude; D000068882:Paliperidone Palmitate; D044367:Phase Transition; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy*; D013024:Soybean Oil / Q000737:chemistry; D013844:Thiazoles / Q000008:administration & dosage; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D014150:Antipsychotic Agents; D003374:Coumarins; D005227:Fatty Acids; D005782:Gels; D007555:Isoxazoles; D011743:Pyrimidines; D013844:Thiazoles; C517282:coumarin 6; D013024:Soybean Oil; D000068882:Paliperidone Palmitate
keywords: In situ forming system; Organogel; Phase inversion; Sustained release; Thermo-sensitive