title: Novel pH sensitive block copolymer micelles for solvent free drug loading.
abstract: Novel pH sensitive biodegradable block copolymers (MPEG-PDLLA-OSM) composed of mono-methoxy poly(ethylene glycol) (MPEG), poly (D,L-lactide) (PDLLA) and sulfamethazine oligomer (OSM) were synthesized via ring-opening polymerization and a dicyclohexyl carboimide (DCC) coupling reaction. These copolymers had a relatively low critical micelle concentration (CMC) due to the strong hydrophobic properties of non-ionized OSM at pH 7.0. Also, the pH sensitive block copolymers showed the micelle-unimer transition due to the ionization-non-ionization of OSM in the pH range (pH 7.2-8.4) above the CMC. Due to the pH sensitive properties of the block copolymer, the hydrophobic drug paclitaxel (PTX) was incorporated into a pH sensitive block copolymer micelle by the pH induced micellization method, without using an organic solvent. The block copolymer micelle prepared by pH induced micellization showed a relatively high PTX loading efficiency, and good stability for 2 d at 37 degrees C. Furthermore, the PTX loaded micelle showed a sustained release of PTX with a small burst in vitro over 2 d. The present results suggest that the pH induced micellization method due to the micelle-unimer transition of the pH sensitive block copolymer would be a novel and valuable drug incorporation tool for hydrophobic and protein drugs, since no organic solvent is involved in the formulation.
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Woo Sun
authors.initials: WS
authors.lastname: Shim
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Choi
authors.forename: Heon-Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Doo Sung
authors.initials: DS
authors.lastname: Lee
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D001673:Biodegradation, Environmental; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D012542:Scattering, Radiation; D012997:Solvents; D013053:Spectrophotometry
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D012997:Solvents; D017239:Paclitaxel