Poly(ethylene glycol)-b-poly(epsilon-caprolactone) micelles containing chemically conjugated and physically entrapped docetaxel: synthesis, characterization, and the influence of the drug on micelle morphology.
Docetaxel (DTX), a chemotherapeutic agent, was coupled to the hydrophobic block of poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-b-PCL) copolymers synthesized by metal free ring-opening polymerization. Synthesis of the copolymers and the copolymer-drug conjugate (PEG-b-PCL-DTX) were confirmed by (1)H NMR and GPC analyses. The PEG-b-PCL-DTX conjugates had a approximately 1:3 drug/copolymer ratio (w/w) and a low critical micelle concentration in aqueous solution (14 mg/L). Encapsulation of DTX in PEG-b-PCL-DTX micelles resulted in an 1840-fold increase in the aqueous solubility of the drug. Release of physically encapsulated DTX from PEG-b-PCL-DTX micelles was slower than drug release from PEG-b-PCL micelles due to the improved compatibility between DTX and the micelle core. Core-conjugated DTX was released over the course of one week indicating that PEG-b-PCL-DTX micelles have the capacity for sustained drug release in the absence of physically encapsulated drug. Importantly, conjugation of DTX to the core-forming block had a profound effect on the morphology of the copolymer aggregates.
Mikhail
Andrew S
AS
Leslie Dan Faculty of Pharmacy, Institute of Biomaterials and Biomedical Engineering, University of Toronto 144 College Street, Toronto, Ontario, Canada M5S 3M2.
Allen
Christine
C
D000970:Antineoplastic Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D000077143:Docetaxel; D005026:Ethylene Glycols / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D011091:Polyesters / Q000737:chemistry*; D043823:Taxoids / Q000737:chemistry*
D000970:Antineoplastic Agents; D005026:Ethylene Glycols; D008823:Micelles; D011091:Polyesters; D043823:Taxoids; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D000077143:Docetaxel