Abstract
The penetration and permeation of the recombinant protein plasminogen activator inhibitor type 2 (PAI-2) in two formulations, one containing a penetration enhancer, into the psoriatic and uninvolved skin of eight patients with plaque-type psoriasis were investigated. Penetration and permeation of PAI-2 were measured by gamma counting and imaging following radiolabelling of a fraction of the applied PAI-2 with 123I. The feasibility of topical delivery of drug to psoriatic plaques was confirmed by the finding that the permeability of psoriatic plaques to radiolabelled PAI-2 (P=0.007) and free 123I (P=0.001) was approximately tenfold higher than the permeability of uninvolved skin. The addition of a penetration enhancer improved the permeation of PAI-2 into psoriatic plaques from an average of 35% to 46% (P=0.005). Occlusion decreased the permeation amount of PAI-2 from 46% to 15% due to losses on the occlusive dressing (P=0.001).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- PA:
-
Plasminogen activator
- PAI-2:
-
Plasminogen activator inhibitor, type 2
- tPA:
-
Tissue plasminogen activator
- uPA:
-
Urinary plasminogen activator
References
Bellen JC, Penglis S, Tsopelas C (1995) Radiolabelling and biodistribution of amiodarone and desethylamiodarone. Nucl Med Biol 7:953–955
Christophers E (1999) Mechanisms in psoriasis and disease heterogeneity. In: Dyall-Smith D, Marks R (eds) Dermatology at the Millennium: Proceedings of the 19th World Congress of Dermatology. Parthenon Publishing Group, New York, pp 55–60
Ghadially R, Reed JT, Elias PM (1996) Stratum corneum structure and function correlates with phenotype in psoriasis. J Invest Dermatol 107:558–564
Gissler HM, Frank R, Kramer MD (1993) Immunohistochemical characterisation of the plasminogen activator system in psoriatic epidermis. Br J Dermatol 128:612–618
Gummer CL (1989) The in vitro evaluation of transdermal delivery. In: Hadgraft J, Guy RH (eds) Transdermal drug delivery. Marcel Dekker, New York, pp 177–196
Hibino T, Matsuda Y, Takahashi T, Goetinck PF (1999) Suppression of keratinocyte proliferation by plasminogen activator inhibitor-2. J Invest Dermatol 112:85–90
Howes D, Guy R, Hadgraft J (1994) Methods for assessing percutaneous absorption. ATLA 24:81–106
Hunter JAA (1995) Diseases of the skin. In: Edwards CRW, Bouchier IAD, Haslett C, Chivers ER (eds) Davidson's principles and practice of medicine. Churchill Livingstone, Edinburgh, pp 948–953
Kruithof EKO, Baker MS, Bunn CL (1995) Biological and clinical aspects of plasminogen activator inhibitor type 2. Blood 86:4007–4024
Lotti T, Bonan P, Cannarozzo G, Fedi AM, Panconesi E (1990) Antipsoriatic therapies inhibit epidermal plasminogen activator activity. Int J Dermatol 29:528–530
Lyons-Giordano B, Loskutoff D, Chen C-S, Lazarus G, Keeton M, Jensen PJ (1994) Expression of plasminogen activator inhibitor type 2 in normal and psoriatic epidermis. Histochemistry 101:105–112
Osamura H, Jimbo Y, Ishimuhara M (1984) Skin penetration of nicotinic acid, methyl nicotinate and butyl nicotinate in the guinea pig. J Dermatol 11:471–481
Pittelkow M (1991) Keratinocyte abnormalities In: Roenigk HH, Maibach HI (eds) Psoriasis, 2nd edn. Marcel Dekker, New York, pp 305–321
Priborsky J, Takayama K, Nagai T, Waitzova D, Elis J (1987) Combination effect of penetration enhancers and propylene glycol on in vitro transdermal absorption of insulin. Drug Des Deliv 2:91–97
Richardson AP, Mountford PJ, Baird AC, Heyderman E, Richardson TC, Coakley AJ (1986) An improved iodogen method of labelling antibodies with 123I. Nucl Med Commun 7:355–362
Rougier A, Dupuis D, Lotte C, Roguet R, Schaefer H (1983) In vivo correlation between stratum corneum reservoir function and percutaneous absorption. J Invest Dermatol 81:275–278
Rougier A, Dupuis D, Lotte C, Roguet R, Wester RC, Maibach HI (1986) Regional variation in percutaneous absorption in man: measurement by the stripping method. Arch Dermatol Res 278:465–469
Saunders DN, Buttigieg KML, Gould A, McPhun V, Baker MS (1998) Immunological detection of conformational neoepitopes associated with the serpin activity of plasminogen activator inhibitor type 2. J Biol Chem 273:10965–10971
Schaefer H, Zesch A, Stuttgen G (1977) Penetration, permeation, and absorption of triamcinolone acetonide in normal and psoriatic skin. Arch Dermatol Res 258:241–249
Schalla W, Schaefer H (1982) Mechanism of penetration of drugs into the skin. In: Brandau R, Lippold BH (eds) Dermal and transdermal absorption. Wissenschaftliche verlagsgesellschaft M B H, Stuttgart, pp 41–72
Spiers EM, Lazarus GS, Lyons-Giordano B (1994) Expression of plasminogen activator enzymes in psoriatic epidermis. J Invest Dermatol 102:333–338
Walters KA (1989) Penetration enhancers and their use in transdermal therapeutic systems. In: Hadgraft J, Guy RH (eds) Transdermal drug delivery. Marcel Dekker, New York, pp 197–246
Yu DK, Elmquist WF, Sawchuck RJ (1985) Pharmacokinetics of propylene glycol in humans during multiple dosing regimens. J Pharm Sci 74:876–879
Acknowledgements
This work was funded by Pi2 Limited, Australia. The authors thank Mr. Frits Moscou, Ms. Gabi Porronik, and Ms. Simone Isaacs for the preparation of trial material, and especially Ms. Jane Kelly, CMAX Pty. Ltd. for organizing the clinical trial. The assistance of the Royal Adelaide Hospital is also gratefully acknowledged. Ms. Shelley Evans provided many helpful comments, and Professor Ross Barnetson helped in the preparation of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gould, A.R., Sharp, P.J., Smith, D.R. et al. Increased permeability of psoriatic skin to the protein, plasminogen activator inhibitor 2. Arch Dermatol Res 295, 249–254 (2003). https://doi.org/10.1007/s00403-003-0425-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-003-0425-4