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Responsive Drug Delivery Systems
- Biomaterials Approaches to Combating Oral Biofilms and Dental Disease

Responsive drug-delivery systems can be classified as open- or closed-loop systems. Open-loop systems are also called pulse or externally regulated systems; the rate of drug released is not dependent upon environmental conditions. The rate of drug released can be controlled and enhanced using external stimulants, such as magnetism and ultrasound. In magnetically-controlled drug delivery devices, small magnetic spheres are embedded in a drug-containing polymer. These spheres release a significant amount of drug when exposed to an oscillating field. Similarly, the release rate also increases when analogous drug-containing polymers are exposed to ultrasound. Ultrasound was found to enhance erosion and degradation of some biodegradable polymers [10] It also can act as an on-off switch as in certain drug delivery systems being developed in the University of Washington Engineered Biomaterials (UWEB) Center [11,12].

In closed-loop systems, or self-regulated systems, the release is in direct response to the conditions detected, be it temperature, type of solvent, pH, or concentration, to name a few. Poly(N-isopropylacrylamide) is a well-known example of a thermo-responsive polymer. At its transition of 32°C, the polymer is soluble in water; but, as temperature is increased, the polymer precipitates and phase separates. Poly(ethylene glycol) and poly(propylene glycol) copolymers as well as poly(lactic acid) and poly(glycolic acid) copolymers also exhibit thermo-responsiveness. These polymers are useful in developing thermogelling systems (e.g., Atridox®), in which the drug is initially dissolved in the liquid form of the polymer at room temperature. When this mixture is injected into the body at 37°C, the polymer turns into a gel, which eventually degrades and releases the drug molecules.

Self-regulating insulin-delivery devices depend on the concentration of glucose in the blood to control the release of insulin. One proposed system would immobilize glucose oxidase (an enzyme) to a pH-responsive polymeric hydrogel, which encloses a saturated insulin solution. At high glucose levels, glucose is catalyzed by glucose oxidase which converts it to gluconic acid, thus lowering the pH. This decrease in pH would cause the membrane to swell, forcing the insulin out of the device [13,14]. A similar pH responsive material could deliver "on-demand" anti-caries therapy at the first drop in pH.

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