Aromatic polyahydrides are clinically used as drug delivery systems for treatment of brain cancer. However, the slow degradation rate and the relative insolubility of the degradation products, especially in organic solvents, are major drawbacks for most biomedical applications. To improve the degradability and solubility of the aromatic polyanhydrides, the aromatic rung substitution was altered from para- to ortho- substituted. As expected, the ortho-substituted polymers have excellent solubility properties and appear to undergo surface erosion. Our evaluation of the degradation products obtained from polyanhydrides led to the design of an alternative polymer with potentially significant applications. Replacing the ether bond with an ester bond yields a polymer that degrades into salicylic acid (SA), an anti-inflammatory, antipyretic and analgesic agent. The proposed polymers are biodegradable (bioresorbable) materials that can be used for short-term dental treatments. The polymer's degradation products (SA) can reduce post-operative inflammation and pain following surgery for periodontal diseases. This system is the first example in which the polymer itself is a controlled-release system: the polymer degrades into SA which has anti-inflammatory and analgesic properties. These polymers may find application in decreasing post-operative pain and inflammation, in addition to creating an environment averse to bacterial processes in periodontal disease. Localized release, unlike orally ingested SA, will conceivably reduce the systemic adverse affects of salicylic acid which is generally prescribed after surgery. Periodontal disease comprise a group of related microbial-induced chronic inflammatory disorders that destroy the tissue supporting the teeth. These diseases can result in loss of normal soft and hard tissue of new health periodontal architecture while reducing the post-operative pain after periodontal surgery. Additionally, lowered pH will be unfavorable to some periodontopathic bacteria. The overall objective of this proposal is to investigate the hypothesis that local delivery of salicylic acid via degradable poly(anhydride-esters) (PAE's) membranes will enhance the healing process.
| Erdmann, L; Macedo, B; Uhrich, K E (2000) Degradable poly(anhydride ester) implants: effects of localized salicylic acid release on bone. Biomaterials 21:2507-12 |
