The long-term objective is to develop a series of oral materials and devices that provide a constant, low level presence of a therapeutic agent while minimizing the need for professional involvement and patient compliance. Toward this goal the initial objective is to demonstrate the feasibility of developing a controlled-release delivery system that can be carried in the mouth. Specifically, the aim is to devise two or more controlled-release antifungal materials as models for delivery systems that can be developed based on 1) microencapsulation of a soluble agent in a biodegradable material in order to control the rate the agent is liberated, 2) dispersion of the encapsulated agent into an amorphous polymer matrix to form a reservoir with a known dose and release rate, and 3) use of mouthguards, dentures or other oral appliances as platforms to carry replaceable reservoir materials. This will enable an effective dose to be delivered, lasting from days to years, without a rigid compliance schedule. The rate of biodegradation, the diffusivity through the matrix polymer, the solubility of the agent and the loading in the reservoir determine the rate and duration of release. By balancing these factors a high level of control over the rate and duration of release is possible. The need for antifungal agents is to control opportunistic oral candidiasis, an infection that frequently strikes the elderly, denture wearers, and a variety of immune-suppressed patients such as AIDS victims, chemotherapy and transplant patients. Many other agents, including antimicrobials, anti-inflammatories, remineralizing agents, hypertension drugs, anesthetics and analgesics could potentially be made more effective if delivered from a controlled-release reservoir carried in the mouth. To achieve these goals two antifungal agents will be used as model compounds. The solubility of their free base forms and of various of their salts will be determined. From these, the more soluble will be chosen for microencapsulation in polylactic acid polymers and copolymers. These hydrolyzable polymers are commercially available in a variety of biodegradation rates. Microcapsules will be prepared using a published sonication/solvent evaporation method. Three dental elastomeric materials -- a silicone, a polyphosphazine and a poly(vinyl acetate-ethylene) -- will be used to form the reservoir matrix. Combinations of agent, encapsulate and matrix will be molded into disks, embedded in acrylic with one surface exposed, and stirred in buffered saline to simulate the oral environment. Release will be followed by UV/visible spectrophotometry. The combinations will be varied to produce a wide range of release rates. The results will be used to characterize the rates and durations of release achievable by this system, and will provide the basis for later development of other controlled-release systems.
