Hydroxypropylmethylcellulose gel application delays Der p 1 diffusion in vitro

B. Diethart, J. C. Emberlin, R. A. Lewis
DOI: 10.4236/ns.2010.22012                

Abstract

Background: A special hydroxypropylmethyl-cellulose powder (Nasaleze?) has been used for the alleviation of nasal symptoms of allergic rhinitis since 1994. The efficacy of the product has been recently proven but the mechanism of action was still largely unknown. The aim of the study was to investigate the hypothesis that the gel formed after moisture absorption in the nose might act as mechanical barrier that prevents allergen diffusion towards the nasal epithelium. Methods: The diffusion of Der p 1 through HPMC and agar gels was measured in vitro after 15, 30, 60, 180 and 360 minutes using ELISA. Agar blocks were used to simulate the nasal mucosa. Control samples without gel layer were obtained. Results: The control samples with no applied gel barrier absorbed 72.2 % of the Der p 1 solution after 15 minutes and 100 % after 60 minutes. In comparison, the HPMC and agar gel layers both significantly delayed Der p 1 diffu-sion. After 15 minutes 0.76 % had diffused through the HPMC gel layer compared to 28.1 % which diffused through the agar layer. After 360 minutes, 14.1 % of the baseline Der p 1 crossed the HPMC gel layer while 100 % had diffused through the agar layer. Conclusions: HPMC gel significantly reduces Der p 1 diffusion in vitro compared to no barrier and an agar gel layer. This is likely to be due to the small mesh size of the polymer network of HPMC and could have important implications for a preventative treat-ment of allergic rhinitis.

Keywords

Allergic Rhinitis; Der p 1;Diffusion Barrier; Hydroxypropylmethylcellulose

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Greiner, A.N. and Meltzer, E.O. (2006) Pharmacologic rationale for treating allergic and nonallergic rhinitis. Journal of Allergy and Clinical Immunology, 118, 985-96.
[2]	Bachau, V. and Durham, S.R. (2004) Prevalence and rate of diagnosis of allergic rhinitis in Europe. European Res-piratory Journal, 24, 758-64.
[3]	Bousquet, J., Khaltaev, N., Cruz, A.A., Denburg, J., Fokkens, W.J., Togias, A.G., Zuberbier,T., Baena-Cag-nani, C.E., Canonica, G.W., van Weel, C. and Agache, I. (2008) Allergic rhinitis and its impact on asthma (ARIA) 2008. Allergy, 63(Suppl.86), S8-S160.
[4]	Carr, W.W., Nelson, M.R. and Hadley, J.A. (2008) Man-aging rhinitis: strategies for improved patient outcomes. Allergy and Asthma Proceedings, 29, 349-57.
[5]	Simoens, S. and Laekeman, G. (2009) Pharmacotherapy of allergic rhinitis: a pharmaco-economic approach. Al-lergy, 64, 85-95.
[6]	Stuck, B.A., Czajkowski, J., Hagner, A.-E., Klimek, L., Verse, T., Hoermann, K. and Maurer, J.T. (2004) Changes in daytime sleepiness, quality of life and objective sleep patterns in seasonal allergic rhinitis: a controlled clinical trial. Journal of Allergy and Clinical Immunology, 113, 663-8.
[7]	Meltzer, E.O. (2001) Quality of life in adults and chil-dren with allergic rhinitis. Journal of Allergy and Clini-cal Immunology, 108, S45-S53.
[8]	Leynaert, B., Neukirch, C., Liard, R., Bousquet, J. and Neukirch, F. (2000) Quality of life in allergic rhinitis and asthma. A population-based study of young adults. American Journal of Respiratory and Critical Care Medicine, 162, 1391-6.
[9]	Passalacqua, G., Bousquet, P.J., Carlsen, K.-H., Kemp, J., Lockey, R.F., Niggemann, B., Pawankar, R., Price, D. and Bousquet, J. (2006) ARIA update: I - Systematic re-view of complementary and alternative medicine for rhinitis and asthma. Journal of Allergy and Clinical Im-munology, 117, 1054-62.
[10]	Emberlin, J.C. and Lewis, R.A. (2006) A double-blind placebo-controlled crossover trial of inert cellulose pow-der by nasal provocation with grass pollen to assess the efficacy of the product in controlling the symptoms of hayfever. EAACI, Vienna, Austria.
[11]	Emberlin, J.C. and Lewis, R.A. (2006) A double blind, placebo controlled trial of inert cellulose powder for the relief of symptoms of hay fever in adults. Current Medi-cal Research and Opinion, 22(2), 275-85.
[12]	Emberlin, J.C. and Lewis, R.A. (2007) A double blind, placebo-controlled cross over trial of cellulose powder by nasal provocation with Der p 1 and Der f 1. Current Medical Research and Opinion, 23(10), 2423-31.
[13]	Josling, P. and Steadman, S. (2003) Use of cellulose powder for the treatment of seasonal allergic rhinitis. Advances in Therapy, 20(4), 213-9.
[14]	Cheong, L.W.S., Heng, P.W.S. and Wong, L.F. (1992) Relationship between polymer viscosity and drug release from a matrix system. Pharmaceutical Research, 9(11), 1510-4.
[15]	Maki, K.C., Carson, M.L., Miller, M.P., Turowski, M., Bell, M., Wilder, D. and Reeves, M.S. (2007) High vis-cosity hydroxypropylmethylcellulose blunts postprandial glucose and insulin responses. Diabetes Care, 30, 1039- 43.
[16]	Reppas, C., Swidan, S.Z., Tobey, S.W., Turowski, M. and Dressman, J.B. (2009) Hydroxypropylmethylcellulose significantly lowers blood cholesterol in mildly hyper-cholesterolemic human subjects. European Journal of Clinical Nutrition, 63, 71-7.
[17]	Bousquet, J., Van Cauwenberge, P., Khaltaev, N. and ARIA (2001) Allergic rhinitis and its impact on asthma. Journal of Allergy and Clinical Immunology, 108, S147-S336.
[18]	Quraishi, S.A., Davies, M.J. and Craig, T.J. (2004) In-flammatory responses in allergic rhinitis: traditional ap-proaches and novel treatment strategies. The Journal of the American Osteopathic Association, 104(5), S7-S15.
[19]	Verbruggen, K., Van Cauwenberge, P. and Bachert, C. (2009) Anti-IgE for the treatment of allergic rhinitis - and eventually nasal polyps? International Archives of Al-lergy and Immunology, 148, 87-98.
[20]	Diethart, B., Emberlin, J.C. and Lewis, R.A. (2008) Hy-droxypropylmethylcellulose gel delays house dust mite allergen (Der p 1) diffusion in vitro. Allergy, 63(Suppl. 88), 551.
[21]	Pluen, A., Netti, P.A., Jain, R.K. and Berk, D.A. (1999) Diffusion of macromolecules in agarose gels: comparison of linear and globular configurations. Biophysical Jour-nal, 77, 542-52.
[22]	Amsden, B. (1998) Solute diffusion in hydrogels. Mechansims and models. Macromolecules, 31, 8382-95.
[23]	Lauffer, M.A. (1961) Theory of diffusion in gels. Bio-physical Journal, 1, 205-13.
[24]	Ferrero, C., Massuelle, D., Jeannerat, D. and Doelker, E. (2008) Towards elucidation of the drug release mecha-nism from compressed hydrophilic matrices made of cellulose ethers. I. Pulse-field-gradient spin-echo NMR study of sodium salicylate diffusivity in swollen hy-drogels with respect to polymer matrix physical structure. Journal of Controlled Release, 128, 71-9.
[25]	Baumgartner, S., Lahajnar, G., Sepe, A. and Kristl, J. (2002) Investigation of the state and dynamics of water in hydrogels of cellulose ethers by 1H NMR spectros-copy. American Association of Pharmaceutical Scientists - PharmSciTech, 3(4), 1-8.
[26]	Fatin-Rouge, N., Starchev, K. and Buffle, J. (2004) Size effects on diffusion processes within agarose gels. Bio-physical Journal, 86, 2710-9.
[27]	Griess, G.A., Guiseley, K.B. and Serwer, P. (1993) The relationship of agarose gel structure to the sieving of spheres during agarose gel electrophoresis. Biophysical Journal, 65, 138-48.
[28]	Xu, G. and Groves, M.J. (2001) Effect of FITC-dextran molecular weight on its release from floating cetyl alco-hol and HPMC tablets. Journal of Pharmacy and Phar-macology, 53, 49-56.
[29]	Puc, M. (2003) Characterisation of pollen allergens. An-nals of Agricultural and Environmental Medicine, 10, 143-9.
[30]	Grote, M., Swoboda, I., Valenta, R. and Reichelt, R. (2005) Group 13 allergens as environmental and immu-nological markers for grass pollen allergy: studies by immunogold field emission scanning and transmission electron microscopy. International Archives of Allergy and Immunology, 136, 303-10.
[31]	Grassi, M. and Grassi, G. (2005) Mathematical modelling and controlled drug delivery: matrix systems. Current Drug Delivery, 2, 97-116.
[32]	Khanvilkar, K., Donovan, M.D. and Flanagan, D.R. (2001) Drug transfer through mucus. Advanced Drug Delivery Reviews, 48, 173-93.
[33]	Viriden, A., Wittgren, B., Andersson, T. and Larsson, A. (2009) The effect of chemical heterogeneity of HPMC on polymer release from matrix tablets. European Journal of Pharmaceutical Sciences, 36(4-5), 392-400.
[34]	Viriden, A., Wittgren, B. and Larsson, A. (2009) Investi-gation of critical polymer properties for polymer release and swelling of HPMC matrix tablets. European Journal of Pharmaceutical Sciences, 36(2-3), 297-309