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.
Highlights
In the drug delivery field, biodegradable polymers can be an ideal drug carrier if they can eventually be absorbed without causing harm or adverse interactions
Initiator is methoxy poly(ethylene glycol) (MPEG); Condition: [Sn(Oct)2]/[Initiator] = 1.2; ([ε-CL] + [lactic acid (LA)])/[toluene] = 2.8 M, 130 ◦C, 24 h; a Determined by proton nuclear magnetic resonance (1H-NMR) spectroscopy; b n-Hexane/diethyl ether (4/1) insoluble part; c Measured by gel permeation chromatography (GPC) (Based on polystyrene standards)
We prepared PCxLyA copolymers to investigate their feasibility as elastic drug carriers for drug delivery systems
Summary
In the drug delivery field, biodegradable polymers can be an ideal drug carrier if they can eventually be absorbed without causing harm or adverse interactions. An ideal drug carrier must possess the ability to remain biocompatible in the human body for controlled lengths of time for medical applications [1–3]. There are many types of synthetic polyesters that possess good biodegradability and biocompatibility. Because of the copolymer’s poor elasticity and flexibility, it is difficult to apply to contracted and relaxed tissues such as muscle, blood vessels, and skin. To overcome this problem, it is necessary to develop a biodegradable polymer which is elastic and flexible [9–12]
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