Abstract
Purpose. Transdermal extraction of clinically relevant analytes offersa potentially non-invasive method of diagnostics. However,development of such a method is limited by the low skin permeability. In thispaper, we report a potential method for non-invasive diagnostics basedon ultrasonic skin permeabilization and subsequent extraction ofinterstitial fluid (ISF) across the skin.Methods. In vivo experiments were performed using Sprague Dawleyrats to assess ultrasound-induced skin permeabilization and subsequentextraction of various analytes. Serum and ISF concentrations of variousanalytes were measured.Results. Application of low-frequency ultrasound rapidly increasedskin permeability. Skin remained in a state of high permeability for atleast three hours. During this period, application of vacuum extractedISF across rat skin in vivo at a rate of 25.7 μl/cm2/hr. We measuredconcentrations of various analytes including glucose, albumin, calcium,urea, triglycerides, lactate, and dextran in transdermally extracted fluid.The composition of the fluid extracted transdermally is similar to thatof ISF.Conclusions. Application of low-frequency ultrasound allows skin permeabilization and extraction of ISF across the skin.
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REFERENCES
D. Klonoff. Non-Invasive Blood glucose monitoring. Diabetes Care. 20:33–437 (1997).
J. N. Roe and B. R. Smoller. Bloodless glucose measurements. Crit. Rev. Ther. Drug Carrier Syst. 15:199–241 (1998).
H. M. Heise. Non-invasive monitoring of metabolites using near infrared spectroscopy: state of the art. Horm. Met. Res. 28:527–534 (1996).
R. L. Bronaugh and H. I. E. Maibach. In Percutaneous Absorption: Mechanisms-Methodology-Drug Delivery, Marcel Dekker, 1989, pp. 1–12.
P. G. Green, M. Flalagan, B. Shroot, and R. H. Guy. Iontophoretic drug delivery. In Pharmaceutical Skin Penetration Enhancement, K.A. Walters, and J. Hadgraft (eds.) Marcel Dekker, New York, 1993, pp. 311–334.
M. R. Prausnitz, V. Bose, R. Langer, and J. C. Weaver. Electroporation of mammalian skin: a mechanism to enhance transdermal drug delivery. Proc. Natl. Acad. Sci. USA. 90:10504–10508 (1993).
S. Mitragotri, D. Edwards, D. Blankschtein, and R. Langer. A mechanistic study of ultrasonically enhanced transdermal drug delivery. J. Pharm. Sci. 84:697–706 (1995).
S. Mitragotri, D. Blankschtein, and R. Langer. Ultrasound-mediated transdermal protein delivery. Science. 269:850–853 (1995).
J. Tamada, N. Bohannon, and R. Potts. Measurement of glucose in diabetic subjects using noninvasive transdermal extraction. Nature Med. 1:1198–1201 (1995).
J. Kost, S. Mitragotri, R. Gabbay, M. Pishko, and R. Langer. Transdermal monitoring of glucose and other analytes using ultrasound. Nature Med, 6:347–350, 2000.
A. C. Laur, J. T. Elder, and N. D. Weiner. Evaluation of the hairless rat as a model for in vivo percutaneous absorption. J. Pharm. Sci. 86:13–18 (1997).
J. Liu, T. N. Lewis, and M. R. Prausnitz. Non-invasive assessment and control of ultrasound-induced membrane permeabilization. Pharm. Res. 15:918–923 (1998).
A. J. Dabbagh and B. Frei. Human suction blister interstitial fluid prevents metal ion-dependent oxidation of low density lipoprotein by macrophages and in cell-free systems. J. Clin. Invest. 96:1958–1966 (1958).
G. K. Menon, K. R. Feingold, and P. M. Elias. Lamellar body secretory response to barrier disruption. J. Invest. Dermatol. 98:279–89 (1992).
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Mitragotri, S., Coleman, M., Kost, J. et al. Transdermal Extraction of Analytes Using Low-Frequency Ultrasound. Pharm Res 17, 466–470 (2000). https://doi.org/10.1023/A:1007537222591
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DOI: https://doi.org/10.1023/A:1007537222591