The broad long term goal of this project is to develop sustained release subcutaneous drug delivery systems in order to achieve continuous dopaminergic stimulation in the treatment of Parkinson's Disease (PD). Pulsatile dopaminergic pharmacokinetics contribute to the variable beneficial effects as well as to adverse effects of treatment of PD and may also contribute to progression of motor side effects such as dyskinesias. Continuous dopaminergic stimulation has therefore been considered an important therapeutic goal. We have developed a proprietary subcutaneous sustained release platform technology based on suspensions of polymer-coated pure drug particles. High drug loading and sustained release kinetics have been achieved with several other drugs and this technology should be readily adaptable to drugs used in the treatment of PD.
Specific aims of this Phase I proposal are to: 1. Formulate sustained release suspensions for the dopaminergic agonist apomorphine. 2. Test the in vitro release-by-time characteristics of these formulations into buffer. 3. Test the in vivo pharmacokinetics and the duration of the formulations in rats. The team of investigators is expert in drug development, polymer chemistry, neuropharmacology, pharmacokinetics and clinical neurology. We have experience in collaboration with large pharmaceutical companies leading to the approval of novel drug delivery systems. This project could lead rapidly to the development of an injectable dosage form that approaches the ideal of continuous dopaminergic stimulation. Completion of these aims will constitute a readily identifiable milestone that will continue in Phase 2, in which we will clarify the potency, duration of action, and safety of the formulation in animal models of PD.
