Low viscosity poly(trimethylene carbonate) for localized drug delivery: rheological properties and in vivo degradation.

The purpose of this study is to examine the potential of low-molecular-weight poly(trimethylene carbonate) for localized delivery for acid-sensitive drugs. Poly(trimethylene carbonate) of various molecular weights is prepared by ring-opening polymerization initiated by octan-1-ol and co-initiated/catalyzed by tin 2-ethylhexanoate. The resultant polymers are amorphous with low glass transition temperatures and viscosities at 37 degrees C that permit their injection through an 18(1\2) G 1.5'' needle. Their biocompatibility and the influence of the molecular weight on the rate of degradation are assessed in vivo through subcutaneous implantation in rats over 40 weeks. The polymers are well tolerated in vivo, and degrade in a fashion dependent on their initial molecular weight. For very low initial molecular weight (620 Da) and for high initial molecular weight (2,400 Da), polymer mass loss is a result of dissolution of the soluble low molecular chains from the bulk. This is contrasted by the results obtained for an intermediate initial molecular weight (1,600 Da), for which polymer mass loss is a result of both dissolution and enzymatic hydrolysis or oxidation as a result of reactive species secreted by activated macrophages at the implant surface.