title: Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel.
abstract: For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel.
authors: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors: Tianyuan
authors: T
authors: Ci
authors: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors: Liang
authors: L
authors: Chen
authors: State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
authors: Lin
authors: L
authors: Yu
authors: 1] State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China [2] Key Laboratory of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors: Jiandong
authors: J
authors: Ding
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D004058:Diffusion; D020100:Hydrogels / Q000737:chemistry*; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D012074:Remission Induction / Q000379:methods; D012995:Solubility; D016896:Treatment Outcome
chemical_list: D020100:Hydrogels; D053769:Nanocapsules; D011091:Polyesters; C000595637:poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D000077146:Irinotecan; D002166:Camptothecin