title: Functionalized hydrophobic poly(glycerol-co-ε-caprolactone) depots for controlled drug release.
abstract: A limitation to many polymer-based drug delivery systems is the lack of ability to customize a particular polymer composition for tailoring drug release kinetics to a specific clinical application. In this study, we investigated the structure-property effects of conjugating various hydrophobic biocompatible side chains to poly(glycerol-co-caprolactone) copolymers with the goal of achieving prolonged and controlled release of a chemotherapeutic agent. The choice of side chain significantly affected the resulting polymer properties including thermal transitions, relative crystallinity (ΔH(f)), and hydrophobicity. Drug-loaded films cast from solutions of polymer and 10-hydroxycamptothecin demonstrated prolonged release from four to over seven weeks depending upon side chain structure without initial burst release behavior. Use of the stearic acid-conjugated poly(glycerol-co-caprolactone) films afforded substantial anticancer activity in vitro for at least 50 days when exposed to fresh cultures of A549 human lung cancer cells over 24 h intervals, correlating well with the measured drug release kinetics.
authors.affiliation: Department of Biomedical Engineering and Chemistry, Boston University, Boston, Massachusetts, United States.
authors.forename: Jesse B
authors.initials: JB
authors.lastname: Wolinsky
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Yohe
authors.forename: Yolonda L
authors.initials: YL
authors.lastname: Colson
authors.forename: Mark W
authors.initials: MW
authors.lastname: Grinstaff
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry; D013499:Surface Properties
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; C552306:poly(glycerol monosterate-co-epsilon-caprolactone); C028098:10-hydroxycamptothecin; D002166:Camptothecin