Star poly(ε-caprolactone)-based electrospun fibers as biocompatible scaffold for doxorubicin with prolonged drug release activity

Abstract

In this work, a novel drug delivery system consisting of poly(ε-caprolactone) (PCL) electrospun fibers containing an ad-hoc-synthesized star polymer made up of a poly(amido-amine) (PAMAM) core and PCL branches (PAMAM-PCL) was developed. The latter system which was synthesized via the ring opening polymerization of ε-caprolactone, starting from a hydroxyl-terminated PAMAM dendrimer and characterized by means of 1H NMR, IR and DSC, was found to be compatible with both the polymer matrix and a hydrophilic chemotherapeutic drug, doxorubicin (DOXO), the model drug used in this work. The preparation of the dendritic PCL star product with an average arm length of 2000g/mol was characterized using IR and 1H NMR measurements. The prepared star polymer possessed a higher crystallinity and a lower melting temperature than that of the used linear PCL. Electrospun fibers were prepared starting from solutions containing the neat PCL as well as the PCL/PAMAM-PCL mixture. Electrospinning conditions were optimized in order to obtain defect free fibers, which was proven by the structural FE-SEM study.PAMAM moieties enhanced the hydrophilicity of the fibers, as proved by comparing the water absorption for the PCL/PAMAM-PCL fibers to that neat PCL fibers. The drug-loaded system PCL/PAMAM-PCL was prepared by directly introducing DOXO into the electrospinning solutions. The DOXO-loaded PCL/PAMAM-PCL showed a prolonged release of the drug with respect to the DOXO-loaded PCL fibers and elicited effective controlled toxicity over A431 epidermoid carcinoma, HeLa cervical cancer cells and drug resistant MCF-7 breast cancer cells. On the contrary, the drug-free PCL/PAMAM-PCL scaffold demonstrated no toxic effects on human dermal fibroblasts, suggesting the biocompatibility of the proposed system which can be used in cellular scaffold applications.