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--PLA) copolymers (PCLA), which display specific rates of flexibility and elasticity. We synthesize the PCLA copolymers by ring-opening polymerization of ε-caprolactone and l-lactide. PCLA copolymers of various compositions were synthesized with 500,000 molecular weight. The PCLA 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 PCLA specimens after up to 20 deformation cycles to 50% elongation. After in vivo implantation, the PCLA implants exhibited biocompatibility, and gradually biodegraded over an eight-week experimental period. Immunohistochemical characterization showed that the PCLA 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 PCLA 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 PCLA implanted in live animals. Finally, we confirmed that PCLA films are usable as biodegradable, elastic drug carriers.