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

Int J Mol Sci. 2017 Mar 21;18(3):671. doi: 10.3390/ijms18030671.

Abstract

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

Keywords: P(CL-co-LA) copolymers; biodegradation; dexamethasone; drug delivery carrier; elastic polyester.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacokinetics
  • Biodegradable Plastics / adverse effects
  • Biodegradable Plastics / chemical synthesis
  • Biodegradable Plastics / chemistry*
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacokinetics
  • Drug Delivery Systems / adverse effects*
  • Drug Liberation
  • Polyesters / adverse effects
  • Polyesters / chemical synthesis
  • Polyesters / chemistry*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Inflammatory Agents
  • Biodegradable Plastics
  • Polyesters
  • poly(epsilon-caprolactone-co-lactide)
  • Dexamethasone