title: Improvement of survival in C6 rat glioma model by a sustained drug release from localized PLGA microspheres in a thermoreversible hydrogel.
abstract: A local drug delivery system based on sustained drug release is an attractive approach to treat brain tumors. We have developed a novel device using drug-incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in thermoreversible gelation polymer (TGP) formulation (drug/PLGA/TGP formulation). TGP forms a gel at body temperature but sol at room temperature. Therefore, when this formulation is injected into the brain tumor, the PLGA microspheres in TGP gel are localized at the injection site and do not diffuse throughout the brain tissue; eventually, sustained drug release from PLGA microspheres is achieved at the target site. In this study, two chemotherapeutic drugs (camptothecin (CPT) or vincristine (VCR)) were incorporated into PLGA microspheres to prepare drug/PLGA/TGP formulations. VCR/PLGA microspheres exhibited the higher encapsulation efficiency than CPT/PLGA microspheres (70.1% versus 30.1%). In addition, VCR/PLGA microspheres showed a higher sustained release profile than CPT/PLGA microspheres (54.5% versus 72.5% release, at 28 days). Therapeutic effect (mean survival) was evaluated in the C6 rat glioma model (control group, 18 days; CPT/PLGA/TGP treatment group, 24 days; VCR/PLGA/TGP treatment group, 33 days). In particular, the VCR/PLGA/TGP formulation produced long-term survivors (>60 days). Therefore, this formulation can be therapeutically effective formulation for the glioma therapy.
authors.affiliation: Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. ozekit@phar.nagoya-cu.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ozeki
authors.forename: Daiki
authors.initials: D
authors.lastname: Kaneko
authors.forename: Kosuke
authors.initials: K
authors.lastname: Hashizawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Imai
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tagami
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okada
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D016650:Fluorescein-5-isothiocyanate; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006358:Hot Temperature; D020100:Hydrogels; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D014750:Vincristine / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D020100:Hydrogels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014750:Vincristine; D016650:Fluorescein-5-isothiocyanate; D002166:Camptothecin