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Characterization of Glucose Dependent Gel-Sol Phase Transition of the Polymeric Glucose-Concanavalin A Hydrogel System

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Abstract

Purpose. The main goal of this study was to synthesize and characterize hydrogels which undergo reversible gel-sol phase transformation in response to changes in glucose concentration in the surrounding environment.

Methods. The glucose-sensitive hydrogels were made by mixing the appropriate concentrations of acrylamide-allyl glucose copolymer and concanavalin A (Con A). To examine their phase reversibility, hydrogels in dialysis membranes were cycled between glucose-free and glucose-containing buffers. The binding affinity of allyl glucose (AG) to Con A was examined by using an equilibrium dialysis technique.

Results. The synthesized hydrogels underwent phase transition to sol in the presence of free glucose in the environment. The concentration of external free glucose (Cf) had to be at least 4 times that of polymer-bound glucose (Cp) to induce phase transition from gel to sol. The binding affinity study showed that binding of AG to Con A was four times stronger than that of free glucose. When Cp in the gel was 0.42 mg/ml or higher, Cf had to be much higher than 4 times Cp to induce phase transition.

Conclusions. The synthesized hydrogels underwent phase transition in the presence of free glucose in the environment, but the phase transition was not linearly dependent on the concentration of free glucose. This non-linear dependence was explained by the increased binding affinity of AG over native glucose to Con A, and the cooperative interactions between polymer-bound glucose and Con A.

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REFERENCES

  1. J. Heller. Chemically self-regulated drug delivery systems, J. Controlled Release 8:111–125 (1988).

    Google Scholar 

  2. M. Brownlee and A. Cerami. A glucose-controlled insulin delivery system: semisynthetic insulin bound to lectin. Science 206:1190–1191 (1979).

    Google Scholar 

  3. S. Y. Jeong, S. W. Kim, M. J. D. Eenink, and J. Feijin. Self-regulating insulin delivery systems I. Synthesis and characterization of glycosylated insulin. J. Controlled Release 1:57–66 (1984).

    Google Scholar 

  4. S. Sato, S. Y. Jeong, J. C. McRea, and S. W. Kim. Self-regulating insulin delivery systems II. In vitro studies. J. Controlled Release 1:67–77 (1984).

    Google Scholar 

  5. J. Kost, T. A. Horbett, B. D. Ratner, and M. Singh. Glucose sensitive membranes containing glucose oxidase: activity, swelling, and permeability studies. J. Biomed. Mater. Res. 19:1117–1133 (1985).

    Google Scholar 

  6. R. A. Siegel. pH-sensitive gels: swelling, equilibria, kinetics, and application for drug delivery. In J. Kost (ed.), Pulsed and self-regulated drug delivery, CRC Press, Boca Raton, FL, 1990, pp. 129–157.

    Google Scholar 

  7. C. K. Kim, E. B. Im, S. J. Lim, Y. K. Oh, and S. K. Han. Development of glucose-triggered pH-sensitive liposomes for a potential insulin delivery. Int. J. Pharm. 101:191–197 (1994).

    Google Scholar 

  8. K. Sawahata, M. Hara, H. Yasunaga, and Y. Osada. Electrically controlled drug delivery systems using polyelectrolyte gels. J. Controlled Release 14:253–262 (1990).

    Google Scholar 

  9. D. S. T. Hsieh, R. Langer, and J. Folkman. Magnetic modulation of release of macromolecules from polymers. Proc. Natl. Acad. Sci. USA 78:1863–1867 (1981).

    Google Scholar 

  10. S. Miyazaki, C. Yokouchi, and M. Tanaka. External control of drug release: controlled release of insulin from a hydrophilic polymer implant by ultrasound irradiation in diabetic rats. J. Pharm. Pharmacol. 40:716–717 (1988).

    Google Scholar 

  11. M. V. Sefton, R. L. Broughton, M. E. Sugamori, and C. L. Mallabone. Hydrophilic polyelectrolytes for the microencapsulation of fibroblasts or pancreatic islets. J. Controlled Release 6:177–187 (1987).

    Google Scholar 

  12. A. M. Sun and G. M. O'Shea. Microencapsulation of living cells-a long-term delivery system. J. Controlled Release 2:137–141 (1985).

    Google Scholar 

  13. H. Uludag, J. E. Babensee, T. Roberts, L. Kharlip, V. Horvath, and M. V. Sefton. Controlled release of dopamine, insulin and other agents from microencapsulated cells. J. Controlled Release 24:3–12 (1993).

    Google Scholar 

  14. P. F. Gores, J. S. Najarian, E. Stephanian, J. J. Lloveras, S. L. Kelley, and D. E. R. Sutherland. Insulin independence in type I diabetes after transplantation of unpurified islets from single donor with 15-deoxyspergualin. Lancet 341:19–21 (1993).

    Google Scholar 

  15. S. J. Lee and K. Park. Synthesis of sol-gel phase-revrsible hydrogels sensitive to glucose. Proc. Intern. Symp. Control. Rel. Bioact. Mater. 21:93–94 (1994).

    Google Scholar 

  16. S. J. Lee and K. Park. Synthesis and characterization of sol-gel phase-reversible hydrogels sensitive to glucose. Polymer Preprints 35(2):391–392 (1994).

    Google Scholar 

  17. S. J. Lee and K. Park. Glucose-sensitive phase-reversible hydrogels. ACS Symposium Series 627:11–16 (1996).

    Google Scholar 

  18. S. J. Lee and K. Park. Synthesis and characterization of sol-gel phase-reversible hydrogels sensitive to glucose. J. Molecular Recognition, in press.

  19. M. J. Taylor, S. Tanna, and G. G. Adams. Insulin delivery system using a novel glucose sensitive formulation. Proc. Intern. Symp. Control. Rel. Bioact. Mater. 22:746–747 (1995).

    Google Scholar 

  20. E. A. Talley, M. D. Vale, and E. Yanovsky. Allyl ethers of carbohydrates III. Ethers of glucose and galactose. J. Am. Chem. Soc. 67:2037–2039 (1945).

    Google Scholar 

  21. W. S. Kim, S. H. Lee, I. K. Kang, and N. K. Park. Release of 8-hydroxyquinoline from copolymers of 8-quinolinyl acrylate and acrylamide. J. Controlled Release 9:281–285 (1989).

    Google Scholar 

  22. M. Fineman and S. D. Ross. Linear method for determining monomer reactivity ratios in copolymerization. J. Polym. Sci. 2:259–262 (1950).

    Google Scholar 

  23. B. B. L. Agrawal and I. J. Goldstein. Protein-carbohydrate interaction VII. Physical and chemical studies on concanavalin A, the hemagglutinin of the jack bean. Arch. Biochem. Biophys. 124:218–229 (1968).

    Google Scholar 

  24. M. Dubois, K. A. Gilles, J. K. Hamilton, P. A. Rebers, and F. Smith. Colorimetric method for determination of sugars and related substances. Anal. Chem. 28:350–356 (1956).

    Google Scholar 

  25. A. J. Kalb and A. Levitski. Metal binding sites of concanavalin A and their role in binding of α-D-glucopyranoside. Biochem. J. 109:669–672 (1968).

    Google Scholar 

  26. G. Scatchard. The attractions of proteins for small molecules and ions. Annal. N. Y. Acad. Sci. 51:660–672 (1949).

    Google Scholar 

  27. L. L. So and I. J. Goldstein. Protein-carbohydrate interaction XX. On the number of binding sites of concanvalin A, the phytohemag-glutinin of the jack bean. Biochim. Biophys. Acta 165:398–404 (1968).

    Google Scholar 

  28. S. Kitano, Y. Koyoma, K. Kataoka, T. Okano, and Y. Sakurai. A novel drug delivery system utilizing a glucose responsive polymer complex between poly(vinyl alcohol) and poly(N-vinyl-2-pyrroli-done) with a phenyl boronic acid moiety. J. Controlled Release 19:162–170 (1992).

    Google Scholar 

  29. J. E. Morris, A. S. Hoffman, and R. R. Fisher. Affinity precipitation of proteins by polyligands. Biotech. Bioeng. 41:991–997 (1993).

    Google Scholar 

  30. K. Nakamae, T. Miyata, A. Jikihara, and A. S. Hoffman. Formation of poly(glycosyloxyethyl methacrylate)-concanavalin A complex and its glucose sensitivity. J. Biomater. Sci. Polym. Edn. 6:79–90 (1994).

    Google Scholar 

  31. J. B. Sumner and S. F. Howell. The identification of the hemagglutinin of the jack bean with concanavalin A. J. Bacteriol. 32:227–237 (1936).

    Google Scholar 

  32. J. L. wang, B. A. Cunningham, and G. M. Edelman. Unusual fragments in the subunit structure of concanavalin A. Proc. Natl. Acad. Sci. USA 68:1124–1130 (1971).

    Google Scholar 

  33. E. Smith and I. J. Goldstein. Protein-carbohydrate interaction V. Further inhibition studies directed toward defining the steriochemical requirements of the reactive sites of concanavalin A. Arch. Biochem. Biophys. 121:88–95 (1967).

    Google Scholar 

  34. P. F. Predki and B. Sarkar. Cooperative interaction of estrogen receptor ‘zinc finger’ domain polypeptides on DNA binding. Biochem. J. 305:805–810 (1995).

    Google Scholar 

  35. S. D. Lewis, J. A. Shafer, and I. J. Goldstein. Kinetic parameters for the binding of p-nitrophenyl-α-D-mannopyranoside to concanavalin A. Arch. Biochem. Biophys. 172:689–695 (1976).

    Google Scholar 

  36. R. D. Farina and R. G. Wilkins. Kinetics of interaction of α-and β-D-monosaccharides with concanavalin A. Biochim. Biophys. Acta 631:428–438 (1980).

    Google Scholar 

  37. V. Horejsi, M. Ticha, and J. Kocourek. Studies on lectins XXXI. Determination of dissociation constants of lectin sugar complexes by means of affinity electrophoresis. Biochim. Biophys. Acta 499:290–300 (1977).

    Google Scholar 

  38. R. D. Poretz and I. J. Goldstein. An examination of the topograghy of the saccharide binding sites of concanavalin A and of the forces involved in complexation. Biochemistry 9:2890–2896 (1970).

    Google Scholar 

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  1. School of Pharmacy, Purdue University, West Lafayette, Indiana, 47907

    Aiman A. Obaidat & Kinam Park

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  1. Aiman A. Obaidat
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Obaidat, A.A., Park, K. Characterization of Glucose Dependent Gel-Sol Phase Transition of the Polymeric Glucose-Concanavalin A Hydrogel System. Pharm Res 13, 989–995 (1996). https://doi.org/10.1023/A:1016090103979

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