Novel polymeric micelles for hydrophobic drug delivery based on biodegradable poly(hexyl-substituted lactides).
Novel amphiphilic methoxy-poly(ethylene glycol)-poly(hexyl-substituted lactides) block copolymers were synthesized by ring-opening polymerization (ROP) of mono and dihexyl-substituted lactide (mHLA and diHLA) in bulk at 100 degrees C in the presence of tin(II) 2-ethylhexanoate (Sn(Oct)(2)) as catalyst and methoxy-poly(ethylene glycol) (MPEG) as initiator. MPEG-PmHLA and MPEG-PdiHLA copolymers of predictable molecular weights and narrow polydispersities were obtained, as shown by (1)H NMR and GPC. DSC experiments showed that the MPEG-PHLA block-copolymer presents a bulk microstructure containing MPEG domains segregated from the PHLA domains. Micelles were successfully prepared from these block copolymers, with sizes ranging from 30 to 80 nm. The critical micellar concentration (CMC) was found to decrease with the increasing number of hexyl groups on the polyester block (MPEG-PLA > MPEG-PmHLA > MPEG-PdiHLA) for copolymers of the same composition and molecular weight. The hydrophobicity of the micelle core in dependence of the number of hexyl groups along the PLA chain was evidenced by absorbance experiments with the incorporation of the dye Nile Red. These novel amphiphilic copolymers are interesting for micellar drug delivery and especially in regard to optimized hydrophobic drug loadings, as it was shown for griseofulvin as a model drug.
Trimaille
Thomas
T
Department of Pharmaceutics and Biopharmaceutics, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
Mondon
Karine
K
Gurny
Robert
R
Möller
Michael
M
D000935:Antifungal Agents / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D004339:Drug Compounding; D005456:Fluorescent Dyes / Q000737:chemistry; D006118:Griseofulvin / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010078:Oxazines / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis*
D000935:Antifungal Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008823:Micelles; D010078:Oxazines; D011091:Polyesters; D011108:Polymers; C492425:methoxy poly(ethylene glycol)-poly(lactide); D006118:Griseofulvin; D011092:Polyethylene Glycols; C033616:poly(lactide); C044808:nile red