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Bioactive Molecules Delivered by Ceramic Nanoparticles Coated with a Film of Polyhydroxyl Oligomers

Published online by Cambridge University Press:  21 February 2011

Nir Kossovsky
Nir Kossovsky*
Affiliation:
Biomaterials Bioreactivity Characterization Laboratory, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, 90024–1732
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Abstract

The structural denaturation of polypeptides and other macromolecular pharmaceuticals upon surface adsorption from an aqueous environment is almost inevitable. Molecular denaturation, coupled with a net increase in entropy, accounts for the net negative ΔG and frequent irreversible nature of surface adsorption. The consequence of this interaction is that surface immobilized drugs lose their dynamic freedom and thus, all too often, their biological activity.

This phenomenon has complicated the development of drug delivery vehicles. In this communication, a drug delivery system based on a novel surface modification process to help reverse the constraining activity of surfaces is described. Beginning with preformed carbon ceramic nanoparticles and self-assembled calcium-phosphate dihydrate particles (colloidal precipitation) to which glassy carbohydrates are then allowed to adsorb as a nanometer thick surface coating, a molecular carrier is formed. The carbohydrate coating functions as a dehydroprotectant and stabilizes subsequently non-covalently bound immobilized members of biochemically reactive surface members such as pharmaceuticals.

Many of the physical properties of this enabling system have been characterized in vitro and in animal models. Antigen delivery, drug delivery, and enzyme stabilization experiments are described.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 394: Symposium Z – Polymers in Medicine and Pharmacy , 1995 , 67
Copyright
Copyright © Materials Research Society 1995

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References

1 Kossovsky, N., Bunshah, R. F., Gelman, A., et al., J Appl Biomat, 1, 289,. (1990).Google Scholar
2 Kossovsky, N., Gelman, A., Sponsler, E. E., Millett, D., J Appl Biomat; 2, 251, (1991).Google Scholar
3 Kossovsky, N., Mat Tech; 8, 3, (1993)Google Scholar
4 Kossovsky, N., Sukiassians, K., Festekjian, A., Nguyen, R., Panossian, A., Derderian, H., Kassabian, A., Gelman, A., SUBMITTED.Google Scholar
5 Kossovsky, N., Nguyen, A., Sukiassians, K. et al., J Coll Interfac Sci,, 166, 350, (1994).Google Scholar
6 Lehninger, A. L., Biochemistry. (Worth Publishers, Inc, New York, 1975); B. T. Nall and K. A. Dill, Conformations and Forces in Protein Folding. (American Association for the Advancement of Science, Washington, D.C., 1991).Google Scholar
7 Israelachvili, J. N., Intermolecular and Surface Forces. (Academic Press, New York, 1985).Google Scholar
8 Kreshech, G. C. and Klotz, I. M., Biochemistry 8, 8 (1969); W. Norde and J. Lyklema, in The Vroman Effect, edited by Bamford, C. H., Cooper, S. L, and Tsuruta, T. (VSP,Utrecht, 1992).Google Scholar
9 Norde, W., presented at the American Chemical Society 207th National Meeting, San Diego, CA, 1994 (unpublished).Google Scholar
10 Franks, F., Bio/technology, 12, 253 (1994).Google Scholar
11 Kusalik, P. G. and Svishchev, I. M., Science, 265, 1219 (1994).Google Scholar
12 Dunitz, J. D., Science, 264, 670. (1994).Google Scholar
13 Ragone, R. and Colonna, G., JAm Chem Soc 116, 2677 (1994).Google Scholar
14 Bryan, W. P., Science, 266, 1726 (1994).Google Scholar
15 Jimenez, R., Fleming, G. R., Kumar, P. V. and Maronceli, M., Nature 369, 471 (1994).Google Scholar
16 Norde, W., Lyklema, J., The Vroman Effect, VSP, Utrecht (1992).Google Scholar
17 Israelachvili, J. N., Intermolecular and Surface Forces, Academic Press, New York (1985).Google Scholar
18 Hnatyszyn, H. J., Kossovsky, N., Gelman, A., Sponsler, E., J Parenteral Sci. Technol, 48, 247, (1994).Google Scholar
19 Hubbard, A. K., Lohr, C. L., Hastings, K., et al., Immunopharm Immunotox 15, 621, (1993).Google Scholar
20 Hoff, H. F., Whitaker, T. E., O'Neil, J., JBio Chem 267, 602, (1992).Google Scholar
21 Haberland, M. E., Fless, G. M., Scanu, A. M., Fogelman, A. M., JBio Chem 267, 4143, (1992).Google Scholar
22 Lewis, R. W., J Am. Pharm. Assoc. 37, 511, (1948).Google Scholar
23 Lewis, R. W., U.S. Patent No. 2,402,902.Google Scholar
24 Loo, Y. H., and Lewis, R. W., Science, 121, 367, (1955).Google Scholar
25 Crowe, J. H., Am. Nat. 105, 563, (1971).Google Scholar
26 Crowe, J. H. et al. Biochim BiophysActa, 947, 367, (1988).Google Scholar
27 Levine, H. and Slade, L., BioPharm. May 36, (1992).Google Scholar
28 Green, J. L. and Angell, C. A., J. Phys. Chem. 93, 2880, (1989).Google Scholar
29 Johnson, L. N., Cheetham, J., McLaughlin, P. J., et. al., Curr Topics Microbiol Immunol, 139, 81, (1988)Google Scholar
30 Quiocho, F. A., Curr. Topics Microbiol. Immunol., 139, 135–150 (1988),Google Scholar
31 Peleg, M., Biotechnol. Prog. 10, 385, (1994).Google Scholar
32 Kossovsky, N., Gelman, A., Sponsler, E. E.: Artif Cells Blood Sub Immobil Biotech, 22, 1994 Google Scholar
33 Gabizon, A.; Catane, R.; Uziely, B., et al., Cancer Res, 54, 987, (1994).Google Scholar
34 Sawhney, A. S., Pathak, C. P., and Hubbell, J. A., Biomaterials, 14, 1008, (1993).Google Scholar
35 Teske, E., Rutteman, G. R., Heerde, P. van, Misdorp, W., Eur J Cancer, 26, 891, (1990).Google Scholar
36 Prestelski, S. J., Tedeschi, N, Arakawa, T, and Carpenter, J. F. Biophy. J,. 65, 661, (1993).Google Scholar
37 Manning, M. C., Patel, K, Borchardt, R. T. Pharmaceut. Res., 6, 903, (1989).Google Scholar
38 Kidd, G., Devorak, J.: Bio/Technology 12, 1328 (1994).Google Scholar
39 Kossovsky, N., Millett, D., Gelman, A., Sponsler, E. and Hnatyszyn, H. J., Bio/Technology, 11,1534, (1993).Google Scholar
40 Hnatyszyn, H. J., Kossovsky, N., Gelman, A. E., et al., SUBMITTED.Google Scholar
41 Kossovsky, N., Gelman, A., Hnatyszyn, H. J., Rajguru, S., Garrell, R. L., Torbati, S., Feeney, S. S., and Chow, G-M, SUBMITTED.Google Scholar
42 Kossovsky, N., Gelman, A., Sponsler, E., Rajguru, S., Torres, M., Mena, E., Ly, K. and Festekjian, A.. J BiomedMater Res 29, 561, (1995).Google Scholar
43 Rini, J. M., Schelze-Gahmen, U. and Wilson, I. A., Science 255, 959, (1992).Google Scholar