Research Project
2122796
With the present compelling need for treatment of narcotic addiction, there is the requirement for a controlled release device that would ensure compliance with a narcotic antagonist regimen, but which could be removable should the patient's circumstance require it. Promising in this regard are bioelastic materials (elastic and plastic protein-based polymers) with compositions [1] that have been shown to be remarkably biocompatible; [2] that do not elicit fibrous encapsulation; [3] that can be loaded with high concentrations of drugs; [4] that are transductional and can be designed such that many different energy inputs can control release by contraction or by swelling and where chemical clocks with half- lives of days to decades could control rate of release by surface swelling; and [5] that would also degrade at the drug-poor swollen surface of the monolith to release natural amino acids. The specific aims of this Phase I SBIR application are: [1] to design and prepare two elastic and one plastic protein-based polymers by chemical synthesis and by genetic engineering and microbial biosynthesis to provide a range of matrices with potential for quite different release profiles; [2] to utilize transitional properties of the bioelastic materials to load antagonist into both viscoelastic phases for possible injection and matrices for implantation by trocar; [3] to determine release profiles without and with chemical clocks which induce controlled swelling with coupled release of antagonist and initiate degradation; and [4] to evaluate rate of degradation of an elastic and a plastic matrix composition as intramuscular implants in the rabbit.
