Levonorgestrel is a steroid widely used for fertility regulation. This program will seek to develop a biodegradable implant which (a) delivers levonorgesterel for 1-2 years, (b) can be administered by trocar, (c) is surgically removable at any time before termination of drug delivery, and (d) does not require surgical removal if left in place after drug depletion. We plan to utilize a poly-L-lactic acid (PLLA) matrix similar to biodegradable polyesters already used in FDA-approved parenteral products. High molecular weight poly-L-lactates (HMW-PLLA) which have recently become available should last for more than two years in vivo. That should make possible biodegradable implants which deliver levonorgestrel for at least one year and remain strong enough to allow removal at any time during the delivery period. Phase I will include in vivo degradation and delivery studies in rabbits, with emphasis on studies of polymer degradation and strength which can help assess whether 19 or 24 month products might be feasible. Phase II will conduct long term tests, confirm removability, investigate the eventual fate of the implants, optimize the design, and prepare the documentation and samples needed for human clinical tests of a biodegradable contraceptive implant.
Currently the most widely used FDA- approved biodegradable polymers, lactide and glycolide polymers and copolymers, can be used to prepare injectable or implantable drug delivery systems lasting up to about a year. Demonstrating that newly available high molecular weight poly-L-lactides can be used to prepare one year contraceptive levonorgestred implants should strongly encourage development of long lasting implants for other drugs.