Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Buccal Mucosal Ulcer Healing Effect of rhEGF/Eudispert hv Hydrogel

  • Park, Jeong-Sook (College of Pharmacy, Chungbuk National University) ;
  • Yoon, Joon-Il (College of Pharmacy, Chungbuk National University) ;
  • Li, Hong (College of Pharmacy, Chungbuk National University) ;
  • Moon, Dong-Cheul (College of Pharmacy, Chungbuk National University) ;
  • Han, Kun (College of Pharmacy, Chungbuk National University)
  • Published : 2003.08.01
Download PDF
⟨ Previous Next ⟩

Abstract

We have studied the effect of rhEGF on the buccal mucosal ulcer healing. rhEGF was rapidly degraded upon incubation with the hamster buccal mucosal homogenates; The degradation of rhEGF was significantly inhibited by sodium lauryl sulfate (SLS). Eudispert hv hydrogel and Polycarbophil 974P hydrogel were prepared for rhEGF delivery and their mucoadhesiveness was measured by the $Instron^R$ method. The mucoadhesive force of Eudispert hv was significantly greater than that of Polycarbophil 974P. Moreover, rhEGF in Eudispert hv hydrogel remained stable for about 2 months. To evaluate the ulcer healing effect of rhEGF, the buccal mucosal ulcer was induced in golden hamsters using acetic acid. At 24 h after administration of rhEGF/Eudispert hv hydrogel, the ulcerous area was decreased compared with rhEGF solution and, as a result, the curative ratio was $36.8\pm5.68$%. By the addition of SLS (0.5%) to Eudispert hv hydrogel, the curative ratio increased 1.5 times. The mechanism of the action was probably due to a combination of protection of the drug against proteases present in mucosa and prolongation of the release of rhEGF from the formulation at the site of action.

Keywords

References

  1. Bower, J. M., Camble, R., Gregory, H., Gerring, E. L., and Willshire, I. R., The inhibition of gastric acid secretion by epidermal growth factor. Experientia, 31, 825-816 (1975) https://doi.org/10.1007/BF01938488
  2. Braford, M. M., A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 72, 248-254 (1976) https://doi.org/10.1016/0003-2697(76)90527-3
  3. Carpenter, G. and Cohen, S., Epidermal growth factor(EGF). Annu. Rev. Biochem., 48, 193-216 (1979) https://doi.org/10.1146/annurev.bi.48.070179.001205
  4. Carpenter, G. and Zendegui, J. G., Epidermal growth factor, its receptor, and related proteins. Exp. Cell Res., 164, 1-10 (1984) https://doi.org/10.1016/0014-4827(86)90449-0
  5. Dibiase, M. D. and Rhodes, C. T., The design of analytical methods for use in topical epidermal growth factor product development. J. Pharm. Pharmacol., 43, 553-558 (1991) https://doi.org/10.1111/j.2042-7158.1991.tb03535.x
  6. Elder, J. B., Ganguli, P. C., Gillespie, I. E., Gerring, E. L., and Gregory, H., Effect of urogastrone on gastrin secretion and plasma gastrin levels in normal subjects. Gut, 16, 887-893 (1975) https://doi.org/10.1136/gut.16.11.887
  7. Gregory, H., Bower, J. M., and Willshire, I. R., Urogastrone and epidermal growth factor. In: Kastrup, K. W., Nielsen, J. H. (Eds.), Growth factors. Pergamon Press, Oxford, pp. 75-84, (1978)
  8. Gregory, H., Isolation and structure of urogastrone and its relationship to EGF. Nature, 257, 325-327 (1975) https://doi.org/10.1038/257325a0
  9. Han, K., Choi, M. S., and Chung, Y. B., Site-specific degradation and transport of recombinant human epidermal growth factor (rhEGF) in the rat gastrointestinal mucosa. Int. J. Pharm., 168, 189-197 (1998a) https://doi.org/10.1016/S0378-5173(98)00097-0
  10. Han, K., Lee, S. J., Kim, J. W., and Chung, Y. B., Oral bioadhecive gels of rhEGF for the healing of gastric ulcers. J. Kor. Pharm. Sci., 28, 99-107 (1998b)
  11. Kim, N. S., Kawata, M., Uchida, T., and Goto, S., Preparation and evaluation of Eudragit gels. III: Rectal gel preparations for sustained release of pentoxifylline. J. Pharm. Sci., 81(6), 537-540 (1992) https://doi.org/10.1002/jps.2600810613
  12. Kirkegaard, P., Olsen, P. S., Poulsen, S. S., and Nexo, E., Epidermal growth factor inhibits cysteamine-induced duodenal ulcers. Gastroenterology, 85, 1277-1283 (1983)
  13. Kiyohara, Y., Komada, F., Iwakawa, S., Hirai, M., Fuwa, T., and Okumura, K., Improvement in wound healing by epidermal growth factor (EGF) ointment. II. Effect of protease inhibitor, Nafamostat, on stabilization and efficacy of EGF in burn. J. Pharmacobio-Dyn., 14, 47-52 (1991) https://doi.org/10.1248/bpb1978.14.47
  14. Konturek, S. J., Cicszkowsk, M., Jaworck, J., Konturek, J., Brzozowski, T., and Gregory, H., Effect of epidermal growth factor on gastrointestinal secretions. Am. J. Physiol., 246, G580-G586 (1984)
  15. Konturek, S. J., Radecki, T., and Brzozowski, T., Gastric cytoprotection by epidermal growth factor. Gastroenterology, 81, 438-443 (1981a)
  16. Konturek, S. J., Brzozowski, T., and Piastucki, I., Role of mucosal prostaglandins and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor. Gut, 22, 927-932 (1981b) https://doi.org/10.1136/gut.22.11.927
  17. Lehr, C. M., Bouwstra, J. A., Tukker, J. J., and Junginger, H. E., Intestinal transmit of bioadhesive microspheres in an in situ loop in the rat A comparative study with copolymers and blends based on polyacrylic acid. J. Control. Rel., 13, 51-62 (1990) https://doi.org/10.1016/0168-3659(90)90074-4
  18. Lue$\beta$en, H. L., Lehr, C. M., Rentel, C. O., Noach, A. B. J., de Boer, A. G., Verhoef, J. C., and Junginger, H. E., Bioadhesive polymers for the peroral delivery of peptide drugs. J. Control. Rel., 29, 329-338 (1994) https://doi.org/10.1016/0168-3659(94)90078-7
  19. Morimoto, K., Akatsuchi, H., Aikawa, R., Morishita, M., and Morisaka, K., Enhanced rectal absorption of [$Asu^{1,7}$]-eel calcitonin in rats using polyacrylic acid acqueous gel base. J. Pharm. Sci., 73, 1366-1368 (1984). https://doi.org/10.1002/jps.2600731010
  20. Morimoto, K., Iwamoto, T., and Morisaka, K., Possible mechanisms for the enhancement of rectal absorption of hydrophilic drugs and polypeptides by aqueous polyacrylic acid gel. J. Pharmacobio-Dyn., 10, 85-91 (1987) https://doi.org/10.1248/bpb1978.10.85
  21. Okabe, S. and Pfeiffer, C. J., Chronicity of acetic acid ulcer in the rat stomach. Digestive Diseases, 17(7), 619-629 (1972) https://doi.org/10.1007/BF02231748
  22. Park, K. and Park, H., Test methods of bioadhesion, Bioadhesive drug delivery systems. CRC Press, Florida, U.S.A., Ch 3, pp. 43-64, (1990)
  23. Patil, S. M., Singh, P., and Maibach, H. I., Cumulative irritancy in man to sodium lauryl sulfate : The overlap phenomenon, Int. J. Pharm., 110, 147-154 (1994) https://doi.org/10.1016/0378-5173(94)90152-X
  24. Senderoff, R. I., Wootton, S. C., Boctor, A. M., Chen, T. M., Giordani, A. B., Julian, T. N., and Radebaugh, G. W., Aqueous stability of human epidermal growth factor 1-48. Pharm. Res., 11(12), 1712-1720 (1994) https://doi.org/10.1023/A:1018903014204
  25. Son, K. H. and Kwon, C. H., Stabilization of human epidermal growth factor (hEGF) in aqueous formulation. Pharm. Res., 12(3), 451-454 (1995) https://doi.org/10.1023/A:1016225207014