Development of amphiphilic diblock copolymers as micellar carriers of taxol

Diblock copolymers of poly(DL-lactide)-block-methoxy polyethylene glycol were synthesized from monomers of DL-lactide (DLLA) and methoxy polyethylene glycol (MePEG) by a ring opening bulk polymerization in the presence of stannous octoate. The copolymer molecular weight and composition were controlled by changing the monomer weight ratio. The copolymers dissolved in water to form polymeric micelles with a hydrophobic poly(DL-lactide) (PDLLA) core and a water soluble MePEG shell. The critical micelle concentrations (CMC), measured by fluorescence techniques, depended on copolymer molecular weight and ranged from millimolar to micromolar. The PDLLA core of the micelle was in a highly viscous state since the H-1-NMR peaks of PDLLA in the copolymers presented in CDCl3 and disappeared in D2O due to the restriction of PDLLA chain mobility. Up to 25% taxol could be loaded into matrices of PDLLA-MePEG (MePEG molecular weight: 2000; DL-lactide/MePEG compositions: 40:60 or 50:50) using the solution casting method. Dissolution of the taxol/copolymer matrices in water, 0.9% NaCl, or 5% dextrose solutions resulted in complete solubilization of taxol within the copolymer micelles. Evidence of strong association or binding of taxol to the PDLLA block of the copolymer even below the polymer CMC is presented.