The most important biodegradable polymers approved by the FDA for parenteral use are polyesters based on lactic and glycolic acids made from cyclic diesters using an organic tin catalyst. These typically resorb over a period of months. To provide materials which resorb more rapidly, low molecular weight polymers are needed, but when made using tin catalysts these are too soft and sticky for most medical applications. BlOTEK has discovered that a harmless compound PO can be used in place of an organotin compound to catalyze the conversion of cyclic lactide and glycolide dimers into low to moderate molecular weight polymers which are non-tacky and rapidly degradable. Phase I prepared a variety of PG initiated polymers purified and characterized the products, measured their physical properties, converted them to microspheres, and compared their resorption rates and tissue response with those of commercial polymers. The new PGI polymers were found to be sufficiently plastic to be formed into useful shapes using hydrostatic pressure alone, without heat, and they were found to be effective at preventing the build-up of static charge during air suspension production of microcapsules. Phase II will now improve the method of synthesis, measure the in vitro and in vivo biological reactivity of four representative polymers, and apply these new materials to the static-free preparation and testing of naltrexone microspheres, and to the compressive production and testing of erythropoietin implants.
A heavy-metal-free method for preparation of lactide and glycolide polymers should lead to products with modified and, in many cases, improved physical and biological properties. This should further widen the usefulness and marketability of these increasingly important biodegradable polymers.
