Abstract
Biocompatible ethylene vinyl acetate copolymer (EVA) was utilized to study the release of an antiviral drug (acyclovir (ACY)) and an antimicrobial drug (doxycycline hyclate (DOH)). Release of both drugs from EVA was measured individually and in combination. The effect of drug combination of DOH and ACY is presented. Additionally, the release rate of DOH after coating of the matrix with a different copolymer, in drug-loading with increasing loads of DOH, and with increases in temperature are also presented. The drugs incorporated in EVA films were prepared from the dry sheet obtained by solvent evaporation of polymer casting solutions with drugs. Drug release from the films was examined for about 12 days in distilled water at 37 °C. Changes in optical density were followed spectrophotometrically. The combination of ACY and DOH resulted in an increased release of ACY by about three times (P < 0.001) while DOH showed a decrease in rate of about two times compared to the individual release rates (P = 0.008). Increases in drug levels of DOH resulted in increases in drug release rates (P = 0.001). The release rate of DOH increased with temperature (P = .001; 27, 32, 37 and 42 °C were studied) and the energy of activation (ΔE ≠ = 56.69 kJ/mol) was calculated using the Arrhenius equation for the diffusion of DOH molecules. Thus, the release rates of drugs were influenced by many factors: drug combination, coating the device, drug-loading, and temperature variation. Therefore it is proposed that controlling these variables should make it possible to obtain therapeutic levels of drugs released from drug loaded polymer, which may be beneficial in treating oral infections.
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Acknowledgements
This work was supported by NIH-NIDCR grant R01 DE 15267. The authors wish to thank Drs. Anton Schindler Senior Scientist, Research Triangle Institute, Polymer Division, Research Triangle Park; and David Barrow Laboratory Manager, Center for Oral & Systemic Diseases, School of Dentistry**, for their valuable contributions to the manuscript. We also thank Dr. John S. Preisser, Research Associate Professor, Department of Biostatistics**, for his help in biostatistical analysis. We finally thank Dr. Wallace Ambrose of the Dental Research Electron Microscopy Center**, for analysis of SEM images of sample morphology. ** University of North Carolina at Chapel Hill
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Ramadevi, A., Padmavathy, T., Stigall, G. et al. EVA copolymer matrix for intra-oral delivery of antimicrobial and antiviral agents. J Mater Sci: Mater Med 19, 721–727 (2008). https://doi.org/10.1007/s10856-007-3109-3
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DOI: https://doi.org/10.1007/s10856-007-3109-3