Preparation of Biodegradable and Elastic Poly(ε-caprolactone-co-lactide) Copolymers and Evaluation as a Localized and Sustained Drug Delivery Carrier

To develop a biodegradable polymer possessing elasticity and flexibility, we synthesized MPEG-b-(PCL-co-PLA) copolymers (PC(x)L(y)A), which display specific rates of flexibility and elasticity. We synthesize the PC(x)L(y)A copolymers by ring-opening polymerization of ε-caprolactone and l-lactide. PC(x)L(y)A copolymers of various compositions were synthesized with 500,000 molecular weight. The PC(x)L(y)A copolymers mechanical properties were dependent on the mole ratio of the ε-caprolactone and l-lactide components. Cyclic tensile tests were carried out to investigate the resistance to creep of PC(x)L(y)A specimens after up to 20 deformation cycles to 50% elongation. After in vivo implantation, the PC(x)L(y)A implants exhibited biocompatibility, and gradually biodegraded over an eight-week experimental period. Immunohistochemical characterization showed that the PC(x)L(y)A implants provoked in vivo inflammation, which gradually decreased over time. The copolymer was used as a drug carrier for locally implantable drugs, the hydrophobic drug dexamethasone (Dex), and the water-soluble drug dexamethasone 21-phosphate disodium salt (Dex(p)). We monitored drug-loaded PC(x)L(y)A films for in vitro and in vivo drug release over 40 days and observed real-time sustained release of near-infrared (NIR) fluorescence over an extended period from hydrophobic IR-780- and hydrophilic IR-783-loaded PC(x)L(y)A implanted in live animals. Finally, we confirmed that PC(x)L(y)A films are usable as biodegradable, elastic drug carriers.