Synthesis of biocompatible poly(ε-caprolactone)-block-poly(propylene adipate) copolymers appropriate for drug nanoencapsulation in the form of core-shell nanoparticles

Abstract

Stavroula G Nanaki1, Kostas Pantopoulos2, Dimitrios N Bikiaris11Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece; 2Lady Davis Institute for Medical Research and Department of Medicine, McGill University, Montreal, Quebec, CanadaAbstract: Poly(propylene adipate)-block-poly(ε-caprolactone) copolymers were synthesized using a combination of polycondensation and ring-opening polymerization of ε-caprolactone in the presence of poly(propylene adipate). Gel permeation chromatography was used for molecular weight determination, whereas hydrogen-1 nuclear magnetic resonance and carbon-13 nuclear magnetic resonance spectroscopy were employed for copolymer characterization and composition evaluation. The copolymers were found to be block while their composition was similar to the feeding ratio. They formed semicrystalline structures, while only poly(ε-caprolactone) formed crystals, as shown by wide angle X-ray diffraction. Differential scanning calorimetry data suggest that the melting point and heat of fusion of copolymers decreased by increasing the poly(propylene adipate) amount. The synthesized polymers exhibited low cytotoxicity and were used to encapsulate desferrioxamine, an iron-chelating drug. The desferrioxamine nanoparticles were self-assembled into core shell structures, had mean particle size <250 nm, and the drug remained in crystalline form. Further studies revealed that the dissolution rate was mainly related to the melting temperature, as well as to the degree of crystallinity of copolymers.Keywords: biocompatible polyesters, poly(ε-caprolactone), poly(propylene adipate), drug encapsulation, desferrioxamine