In vitro release of colchicine using poly(phosphazenes) : The development of delivery systems for musculoskeletal use

ABSTRACTA colchicine release system utilizing biodegradable poly (phosphazenes) was investigated in vitro for intra-articular administration. Polymer degradation and drug release studies were performed on colchicine-loaded poly (phosphazenes) containing either imidazotyl (I-PPHOS) or ethyl gtycinato (EG-PPHOS) side chain substituents over a 21-day period. To study the effects of an implantable colchi-cine-PPHOS delivery system on local musculoskeletal tissue in vitro, osteoblast-like cells were grown on the matrices. Colchicine release was 20% for I-PPHOS and 60% for EG-PPHOS over the 21-day period. Release appeared to proceed through a combination of diffusional and degradative mechanisms. Environmental scanning electron microscopy (ESEM) studies revealed large pores in the drug-depleted devices in contrast to the control matrices without drug, which may have contributed to the release seen, especially with ethyl glycinato-containing matrices. Cell growth on matrices containing colchicine was significant...