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 (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.
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea. jhp@ajou.ac.kr.
Ji Hoon
JH
Park
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea. acousticjazz@ajou.ac.kr.
Bo Keun
BK
Lee
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea. hpt88@ajou.ac.kr.
Seung Hun
SH
Park
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea. kmg@ajou.ac.kr.
Mal Geum
MG
Kim
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea. dlwlswlsdndn@ajou.ac.kr.
Jin Woo
JW
Lee
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea. leeyn3679@ajou.ac.kr.
Hye Yun
HY
Lee
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea. hblee@ajou.ac.kr.
Hai Bang
HB
Lee
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea. jhkim@ajou.ac.kr.
Jae Ho
JH
Kim
Department of Molecular Science and Technology, Ajou University, Suwon 443-759, Korea. moonskim@ajou.ac.kr.
Moon Suk
MS
Kim
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D063566:Biodegradable Plastics / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000009:adverse effects*; D065546:Drug Liberation; D011091:Polyesters / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D063566:Biodegradable Plastics; D011091:Polyesters; C505727:poly(epsilon-caprolactone-co-lactide); D003907:Dexamethasone
P(CL-co-LA) copolymers; biodegradation; dexamethasone; drug delivery carrier; elastic polyester