Antiviral and Antimicrobial Drug Release from EVA copolymer

Objective: Current treatment for HIV-associated oral infections consists of heavy systemic doses (>3g per day) of antimicrobial and antiviral drugs leading to serious side effects and morbidity. The objective of the present study is to develop a device to deliver drugs intraorally at therapeutic levels over extended periods of time to treat oral diseases. Methods: The release rates of an antiviral and an antimicrobial drug namely ganciclovir (GCY) and chlorhexidine diacetate (CHDA) from ethylene vinyl acetate copolymer (EVA) were investigated individually and in combination. Polymer casting solutions were prepared by dissolving EVA copolymer and 2.5wt% drugs in dichloromethane. Different concentrations of GCY: 1.0, 2.5, 5.0, 7.5% in the EVA matrix were used to study the effect of drug loading on the drug release rate. Thin square films of 2×2 cm with a thickness of 0.8mm were cut from the dry sheet obtained by solvent evaporation. The rate of individual drug release at 37°C in water was measured by UV-spectrophotometer while the mixtures of drugs were measured by high performance liquid chromatography (HPLC). Results: The release rate of CHDA is slightly higher than that of GCY both individually and in combination. In the combinations, the release of the drug is proportional to its concentration in the mixture. Also, the increase in drug concentration in polymer was studied. Drug release rates increased steadily with increase in drug load. Conclusions: Studies showed that there was a sustained release of drug over an extended period of time, thus providing a basis for oral treatment. It is also possible to alter the rate of drug release in the EVA matrix to a desired value by: (1) changing the drug loading and (2) altering the relative ratio of the drugs.

The work is supported by NIH-NIDCR grant R01 DE 15267.