Biodegradable lactide polymers: Synthesis, degradation, and controlled drug release properties.

摘要

Biodegradable polylactide has been widely employed in medical and surgical applications, such as temporary tissue fixation, controlled drug release, and tissue engineering. Our investigation was aimed at obtaining a better understanding of polylactide synthesis, its degradation properties, the release mechanisms of water soluble drugs from a polylactide matrix, and the development of a biodegradable controlled antibiotic release device for treatment of bone infection in orthopaedic surgery. Biodegradable poly(DL-lactide), poly(L-lactide), poly(L-lactide-co-{dollar}epsilon{dollar}-caprolactone), and poly(DL-lactide-co-{dollar}epsilon{dollar}-caprolactone) were synthesized by a ring opening polymerization procedure. The drawability and melt processability of polylactide were modified by varying the polymer molecular weight and its distribution, and copolymerization of lactide with {dollar}epsilon{dollar}-caprolactone. The degradation study showed that polylactide was thermally unstable and its hydrolytic degradation rate was primarily affected by the degree of polymer purity. In order to obtain a biodegradable controlled antibiotic release device with promising properties, various matrix types of devices with different drug loadings were manufactured and tested in vitro. Coated PDLLA cylinders, with drug loadings below the percolation threshold, gave the most promising release properties in terms of a small initial burst, a gradual, and an easily adjustable release. The drug release mechanisms were found to be pure diffusion-through-channels, osmotic pressure induced diffusion-through-channels, and polymer degradation. Drug loading, drug particle size, and device length of the coated cylinder were three critical factors affecting the release properties. The coated cylindrical PDLLA device also gave good release profiles for delivery of the protein albumin, as well as the hormones testosterone and estradiol-17B. The significance of these studies is that they have increased our knowledge of biodegradable lactide polymers, particularly their synthesis, degradation, and applications in controlled drug release.