The characterization of novel polymeric paste formulations for intratumoral delivery

Abstract

The objective of this work was to characterize a polymeric paste formulation of the anticancer drug paclitaxel that was injectable through a narrow gauge needle at room temperature and set to a solid implant in vivo for the intratumoral treatment of localized cancer. Pastes were manufactured from a triblock copolymer composed of poly(D,L-lactide-co-caprolactone)-block- polyethylene glycol-block-poly(D,L-lactide-co-caprolactone) (PLC-PEG-PLC) or triblock blended with a low molecular weight polymer methoxypolyethylene glycol (MePEG). Characterization of pastes was performed using differential scanning calorimetry (DSC), gel permeation chromatography (GPC) and drug release studies. Paste integrity in water was measured by determining the degree of fragmentation under initial agitation. MePEG was found to be miscible with the triblock polymer and paclitaxel dissolved in various blends of these polymers up to 15% drug loading. Pastes composed of 40:60 triblock:MePEG blends and 10% paclitaxel were found to inject through a 23-gauge needle and set to a solid pellet in phosphate-buffered saline at 37°C. Such pellets released paclitaxel in a controlled manner over 7 weeks. Pastes composed of 40:60 triblock:MePEG blends containing 10% paclitaxel are proposed as suitable injectable formulations of the drug for intratumoral therapy. © 2003 Elsevier B.V. All rights reserved.