Abstract
A series of polyethylene glycols (PEGs) ranging in molecular weight from near 600 to over 2000 daltons was used to study the effects of three absorption enhancers (sodium glycocholate, sodium lauryl sulfate, and polyoxyethylene 9 lauryl ether) on the molecular weight permeability profile of the nasal mucosa of the rat. Molecular weight–permeability properties were studied both by following changes in the excretion of the polyethylene glycols as a function of their molecular size and by examining the nasal mucosa for morphologic changes following exposure to the PEG/enhancer mixtures. Each absorption enhancer was found to affect the mucosa and its permeability in a unique manner. At a 1% concentration, sodium glycocholate only slightly affects tissue morphology and does not significantly alter the molecular weight permeability profile of the mucosa. In contrast, 1% sodium lauryl sulfate causes severe alteration of the mucosa and also greatly increases the absorption of both the PEG 600 and the PEG 2000 oligomers. Polyoxyethylene 9 lauryl ether was found to exert its action in a concentration-dependent manner. At a concentration of 0.1%, few changes were seen in either mucosal integrity or permeability. At a 1% concentration, however, a significant alteration in the structure of the mucosal tissues as well as a profound increase in the permeability of the mucosa to the PEGs was observed. Correlation of mucosal integrity with the effectiveness of an enhancer indicates that some of these compounds appear to be acting by altering the structure of the mucosa. Others, which appear to exert a less damaging effect on the mucosal cells themselves, achieve their greatest absorption enhancement when changes in cell-to-cell adhesion in the mucosa are observed. These results indicate that the paracellular routes may play an important role in large molecule absorption through the nasal mucosa.
Similar content being viewed by others
REFERENCES
J. Tonndorf, R. W. Hyde, H. I. Chinn, and J. E. Lett. Ann. Otol. Rhinol. Laryngol. 62:630–639 (1953).
Y. Kaneo. Acta Pharm. Suec. 20:379–388 (1983).
A. A. Hussain, S. Hirai, and R. Bawarshi. J. Pharm. Sci. 68:1196(1979).
R. T. Woodyatt. J. Metab. Res. 2:793 (1922).
M. D. Donovan, G. L. Amidon, and G. L. Flynn. Pharm. Res. 7:863–868 (1990).
C. McMartin, L. E. F. Hutchinson, R. Hyde, and G. E. Peters. J. Pharm. Sci. 76:535–540 (1987).
A. N. Fisher, K. Brown, S. S. Davis, G. D. Parr, and D. A. Smith. J. Pharm. Pharmacol. 39:357–362 (1987).
Y. Maitani, Y. Machida, and T. Nagai. Int. J. Pharm. 49:23–27 (1989).
S. Hirai, T. Yashiki, and H. Mima. Int. J. Pharm. 9:165–172 (1981).
G. S. Gordon, A. C. Moses, R. D. Silver, J. S. Flier, and M. C. Carey. Proc. Natl. Acad. Sci. USA 82:7419–7423 (1985).
J. P. Longenecker, A. C. Moses, J. S. Flier, R. D. Silver, M. C. Carey, and E. J. Dubovi. J. Pharm. Sci. 76:351–355 (1987).
S. C. Raehs, J. Sandow, K. Wirth, and H. P. Merkle. Pharm. Res. 5:689–693 (1988).
M. Mishima, Y. Wakita, and M. Nakano. J. Pharmacobiodyn. 10:624–631 (1987).
P. Tengamnuay and A. K. Mitra. Presented at the American Association of Pharmaceutical Scientists 3rd Annual Meeting, Orlando, FL, 1988.
A. Hussain, S. Hirai, and R. Bawarshi. J. Pharm. Sci. 69:1411–1413 (1980).
S. Hirai, T. Ikenaga, and T. Matsuzawa. Diabetes 27:296–299 (1978).
Y. Hirata, T. Yokosuka, T. Kasahara, M. Kikuchi, and K. Ooi. Excerpt. Med. Int. CS 468:319–326 (1979).
B. J. Aungst, N. J. Rogers, and E. Shefter. J. Pharmacol. Exp. Ther. 244:23–27 (1988).
A. E. Pontiroli, M. Alberetto, A. Secchi, G. Dossi, I. Bosi, and G. Pozza. Br. Med. J. 284:303–306 (1982).
A. E. Pontiroli, M. Alberetto, and G. Pozza. Br. Med. J. 287:462–463 (1983).
A. E. Pontiroli, M. Alberetto, and G. Pozza. Acta Diabetol. Lat. 22:103–110(1985).
S. Hirai, T. Yashiki, and H. Mima. Int. J. Pharm. 9:173–184 (1981).
V. H. L. Lee and S. D. Kashi. Proc. Int. Symp. Control. Rel. Bioact. Mater. 14:53–54 (1987).
G. S. M. J. E. Duchateau, J. Zuidema, and F. W. H. M. Merkus. Int. J. Pharm. 31:193–199 (1986).
F. H. Kirkpatrick and H. E. Sandberg. Biochim. Biophys. Acta 298:209–218(1973).
F. H. Kirkpatrick, S. E. Gordesky, and G. V. Marinetti. Biochim. Biophys. Acta 345:154–161 (1974).
B. J. Aungst and N. J. Rogers. Pharm. Res. 5:305–308 (1988).
W. A. Lee, R. E. Ennis, and L. C. Foster. Proc. Int. Symp. Control. Rel. Bioact. Mater. 15:70–71 (1988).
R. Salzman, J. E. Manson, G. T. Griffing, R. Kimmerle N. Ruderman, A. McCall, E. I. Stoltz, C. Mullin, D. Small, J. Armstrong, and J. C. Melby. N. Engl. J. Med. 312:1078–1084 (1985).
D. Hollander, S. Koyama, V. Dadufalza, D. Q. Tran, P. Krugliak, T. Ma, and K.-Y. Ling. J. Lab. Clin. Med. 113:505–515 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Donovan, M.D., Flynn, G.L. & Amidon, G.L. The Molecular Weight Dependence of Nasal Absorption: The Effect of Absorption Enhancers. Pharm Res 7, 808–815 (1990). https://doi.org/10.1023/A:1015904730599
Issue Date:
DOI: https://doi.org/10.1023/A:1015904730599