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A Semisynthetic Quillaja Saponin as a Drug Delivery Agent for Aminoglycoside Antibiotics

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Abstract

Purpose. The purpose of this study was to investigate the utility of a purified, semisynthetic saponin, DS-1, prepared by deacylation of a naturally occurring saponin from the bark of the Quillaja saponaria Molina tree, as a permeation enhancer for mucosal delivery of the aminoglycosides, gentamicin and tobramycin.

Methods. Gentamicin or tobramycin formulations, with and without DS-1, were administered to rats nasally, ocularly, and rectally. Serum aminoglycoside levels following mucosal application were compared with those administered intramuscularly. Gentamicin formulations, with and without DS-1, were administered intranasally to mice 60 minutes after a lethal bacterial challenge. To ascertain nasal irritation potential, DS-1 nosedrops were administered to rats twice daily for 7 days in the right nostril only. Comparison of the left (internal control) and right nostril was made with a control group that received only buffer.

Results. Significant transport across mucous membranes was only observed in formulations containing DS-1. This effect on drug delivery was transient. Administration of an intranasal gentamicin/ DS-1 formulation reversed the lethal bacterial challenge in mice, demonstrating that biological activity was retained after absorption. Nasal irritation was not observed in groups receiving DS-1 nose-drops, which were identical to control groups.

Conclusions. DS-1 has potential as a transmucosal delivery agent for the aminoglycoside antibiotics.

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REFERENCES

  1. A. G. Gilman, T. W. Rall, A. S. Nies, and P. Taylor. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th edition, Pergamon Press, New York, 1990.

    Google Scholar 

  2. D. M. Poretz. Outpatient Use of Intravenous Antibiotics. Amer. J. Med. 97 (suppl. 2A):1–2 (1994).

    Google Scholar 

  3. R. J. Roberts. Issues and Problems Associated with Drug Delivery in Pediatric Patients. J. Clin. Pharmacol. 34:723–724 (1994).

    Google Scholar 

  4. G. S. Gordon, A. C. Moses, R. D. Silver, J. S. Flier, and M. C. Carey. Nasal Absorption of Insulin: Enhancement by Hydrophobic Bile Salts. Proc. Natl. Acad. Sci. USA 82:7419–7423 (1985).

    Google Scholar 

  5. A. E. Pontiroli, M. G. Perfetti, B. Fattor, and G. Pozza. Effect of Intranasal Growth Hormone-Releasing Hormone and Corticotropin-Releasing Hormone Administration on Growth Hormone and Cortisol Release: Improved Bioavailability by Means of Sodium-Glycocholate. J. Clin. Endocrinol. Metab. 68:821–824 (1989).

    Google Scholar 

  6. M. Mishima, Y. Wakita, and M. Nakano. Promotion of Nasal Absorption of Insulin by Glycyrrhetinic Acid Derivatives. J. Pharmacobio-Dyn. 12:31–36 (1989).

    Google Scholar 

  7. P. A. Baldwin, C. K. Klingbeil, C. J. Grimm, J. P. Longenecker. The Effect of Sodium Tauro-24,25-Dihydrofusidate on the Nasal Absorption of Human Growth Hormone in Three Animal Models. Pharm. Res. 7:547–552 (1990).

    Google Scholar 

  8. D. J. Pillion, J. D. Bartlett, E. Meezan, M, Yang, R. J. Crain, and W. E. Grizzle. Systemic Absorption of Insulin Delivered Topically to the Rat Eye. Invest. Ophthalmol. Vis. Sci. 32:15–21 (1991).

    Google Scholar 

  9. G. C. Y. Chiou and C. Y. Chuang. Improvement of Systemic Absorption of Insulin through Eyes with Absorption Enhancers. J. Pharm. Sci. 78:815–818 (1989).

    Google Scholar 

  10. C. R. Kensil, U. Patel, M. Lennick, and D. Marciani. Separation and Characterization of Saponins with Adjuvant Activity from Quillaja saponaria Molina Cortex. J. Immunol. 146:431–437 (1991).

    Google Scholar 

  11. C. R. Kensil, S. Soltysik, U. Patel, and D. J. Marciani. Structure/Function Relationship in Adjuvants from Quillaja saponaria Molina. In: R. M. Chanock, H. S. Ginsberg, F. Brown, R. A. Lerner, (eds.), Vaccines 92, Cold Spring Harbor Laboratory Press, Cold Spring, New York, 1992, pp. 35–40.

    Google Scholar 

  12. M. J. Newman, J. Y. Wu, B. H. Gardner, K. J. Monroe, D. Leombruno, J. Recchia, C. R. Kensil, and R. T. Coughlin. Saponin Adjuvant Induction of Ovalbumin Specific CD8+ Cytotoxic T-Lymphocyte Responses. J. Immunol. 148:2357–2362 (1992).

    Google Scholar 

  13. J. Y. Wu, B. H. Gardner, C. I. Murphy, J. Seals, C. R. Kensil, J. Recchia, G. A. Beltz, G. W. Newman, and M. J. Newman. Saponin Adjuvant Enhancement of Antigen-Specific Immune Responses to an Experimental HIV-1 Vaccine. J. Immunol. 148:1519–1525 (1992).

    Google Scholar 

  14. R. Higuchi, Y. Tokimitsu, T. Fujioka, T. Komori, T. Kawasaki, and D. G. Oakenful. Structure of Deacylsaponins Obtained from the Bark of Quillaja Saponaria. Phytochemistry 26:229–235 (1987).

    Google Scholar 

  15. D. J. Pillion, J. Recchia, P. Wang, D. J. Marciani, and C. R. Kensil. DS-1, A Modified Quillaja Saponin, Enhances Ocular and Nasal Absorption of Insulin. J. Pharm. Sci. (In press)

  16. C. R. Kensil, S. Soltysik, and D. J. Marciani. Methods for Enhancing Drug Delivery with Modified Saponins. U.S. Patent Number 5,273,965 (1993).

  17. W. S. York, A. G. Darvil, M. McNeil, T. T. Stevenson, and P. Albersheim. Plant Molecular Biology. In: A. Weissbach and H. Weissbach (eds.), Methods in Enzymology, Academic Press, New York, 1986, volume 118, pp. 3–40.

    Google Scholar 

  18. E. DeVendittis, G. Palumbo, G. Parlato, and V. Bocchini. A Fluorimetric Method for the Estimation of the Critical Micelle Concentration of Surfactants. Anal. Biochem. 115:278–286 (1981).

    Google Scholar 

  19. M. E. Jolley, S. D. Stroupe, C. J. Wang, H. N. Panas, C. L. Keegan, R. L. Schmidt, and K. S. Schwenzer. Fluorescence Polarization Immunoassay. I. Monitoring Aminoglycoside Antibiotics in Serum and Plasma. Clin. Chem. 27:1190–1197 (1981).

    Google Scholar 

  20. C. O. Onyeji, D. P. Nicolau, C. H. Nightingale, R. Quintiliani. Optimal Times above MICs of Ceftibuten and Cefaclor in Experimental Intra-Abdominal Infections. Antimicrobial Agents and Chemotherapy 38:1112–1117 (1994).

    Google Scholar 

  21. G. S. M. J. E. Duchateau, J. Zuidema, and F. W. H. M. Merkus. Bile Salts and Intranasal Drug Absorption. Intl. J. Pharmaceutics 31:193–199 (1986).

    Google Scholar 

  22. A. Rubinstein. Intranasal Administration of Gentamicin in Human Subjects. Antimicrobial Agents and Chemotherapy 23:778–779 (1983).

    Google Scholar 

  23. J. P. Longenecker, A. C. Moses, J. S. Flier, R. D. Silver, M. C. Carey, and E. J. Dubovi. Effects of Sodium Taurodihydrofusidate on Nasal Absorption of Insulin in Sheep. J. Pharm. Sci. 76:351–355 (1987).

    Google Scholar 

  24. D. J. Pillion, C. R. Kensil, J. A. Amsden, and J. Recchia. A Structure/Function Relationship Among Quillaja Saponins Serving as Excipients for Nasal and Ocular Delivery of Insulin. Submitted for publication.

  25. F. W. H. M. Merkus, N. G. M. Schipper, W. A. J. J. Hermens, S. G. Romeijn, and J. C. Verhoef. Absorption Enhancers in Nasal Drug Delivery; Efficacy and Safety. J. Controlled Release 24:201–208 (1993).

    Google Scholar 

  26. S. Gizurarson and E. Bechgaard. Intranasal Administration of Insulin to Humans. Diabetes Res. Clin. Pract. 12:71–84 (1991).

    Google Scholar 

  27. M. T. Scott, M. Goss-Sampson, and R. Bomford. Adjuvant Activity of Saponin: Antigen Localization Studies. Int. Archs. Allergy Appl. Immun. 77:409–412 (1985).

    Google Scholar 

  28. R. Strobbe, G. Charlier, A. van Aert, J. Debecq, and J. Leunen. Studies about the Adjuvant Activity of Saponin Fractions in Foot-and-Mouth Disease Vaccine. II Irritation and Adjuvant Activity of Saponin Fractions Obtained by Chromatography on Sephadex G-100. Arch. Exper. Vet. Med. 28:385–392 (1974).

    Google Scholar 

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Authors
  1. Joanne Recchia
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  2. Maria H. A. Lurantos
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  3. Jennifer A. Amsden
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  4. James Storey
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  5. Charlotte R. Kensil
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Recchia, J., Lurantos, M.H.A., Amsden, J.A. et al. A Semisynthetic Quillaja Saponin as a Drug Delivery Agent for Aminoglycoside Antibiotics. Pharm Res 12, 1917–1923 (1995). https://doi.org/10.1023/A:1016235705448

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