ORAL CONTROLLED-RELEASE DELIVERY SYSTEMS

  • Rawls, Henry R (PI)

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date4/1/913/31/93

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)
  • Dentistry(all)

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