IN-VITRO CHARACTERIZATION AND IN-VIVO EFFICACY OF A PROSTAGLANDIN-E(2) POLY(ORTHO ESTER) IMPLANT FOR BONE-GROWTH PROMOTION

Prostaglandin E2 (PGE2) is a known stimulator of bone growth, yet when systemically administered at efficacious levels there are serious sid e effects. It was hypothesized that local delivery of a low dose of PG E, would increase the rate of bone growth without systemic side effect s. Biodegradable poly(ortho ester) (P(OE)) implants (4 mg, diameter= 2 mm, height = 1 mm) containing three different loadings of PGE2 (0.81, 0.035 or 0.0032% PGE2 w/w) were fabricated, characterized for in vitr o release, and implanted in vivo in rat tibiae for 8 days. The PGE, re lease rate in vitro increased with increased initial loading of PGE2; this increase was faster than predicted by a diffusional matrix releas e mechanism and was consistent with acid catalyzed P(OE) degradation i n response to the PGE2. In vivo, bone was examined at the end of the 8 day implantation period for new growth. These studies showed that the implants with the two highest loadings significantly enhanced (up to 3-fold) localized bone growth with no observable side effects in any o f the treatment groups. This approach may be useful for enhancing bone growth in clinical situations which require bone augmentation or repa ir.