Radio Frequency-Microchannels for Transdermal Delivery: Characterization of Skin Recovery and Delivery Window
Yossi Kam, Hagit Sacks, Keren Mevorat Kaplan, Meir Stern, Galit Levin
DOI: 10.4236/pp.2012.31004   PDF    HTML   XML   5,251 Downloads   10,356 Views   Citations


Transdermal delivery through Radio-Frequency-MicroChannels (RF-MCs) was proven to be a promising delivery method for hydrophilic drugs and macromolecules that must be injected. An important issue in assessing this technology is the life span of the microchannels (MCs). The time window in which the MCs remain open affects the delivery rate and determine the effective delivery duration. The present work focused on the characterization of the ViaDor-MCs recovery and closure process by measurements of transepidermal water loss (TEWL) before and after the formation of MCs, evaluation of the delivery window, and assessment of skin histology. Testosterone-cyclodextrin complex was used as the model drug for evaluation of the transdermal delivery. In-vitro permeation system and in-vivo guinea pig animal model were used in the delivery studies. Our findings demonstrate the recovery process of MCs created by the RF ablation technology. The observed gradual skin recovery affected the transdermal delivery rate. A significant transdermal delivery was shown up to 24 hrs post device application suggesting that an extended delivery of water soluble drugs, including macromolecules, is possible. The histology assessments demonstrated repair and healing of the induced MCs indicating that the RF micro-channeling technology is minimally invasive, transient in nature with no resulting skin trauma.

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Y. Kam, H. Sacks, K. Kaplan, M. Stern and G. Levin, "Radio Frequency-Microchannels for Transdermal Delivery: Characterization of Skin Recovery and Delivery Window," Pharmacology & Pharmacy, Vol. 3 No. 1, 2012, pp. 20-28. doi: 10.4236/pp.2012.31004.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] M. R. Prausnitz and R. Langer, “Transdermal Drug De-livery,” Nature Biotechnology, Vol. 26, No. 11, 2008, pp. 1261-1268. doi:10.1038/nbt.1504
[2] M. R. Prausnitz, S. Mitragotri and R. Langer, “Current Status and Future Potential of Transdermal Drug Delivery,” Nature Reviews Drug Discovery, Vol. 3, No. 2, 2004, pp. 115-124. doi:10.1038/nrd1304
[3] M. B. Brown, et al., “Dermal and Transdermal Drug Delivery Systems: Current and Future Prospects,” Drug Delivery, Vol. 13, No. 3, 2006, pp. 175-187. doi:10.1080/10717540500455975
[4] A. Samad, et al., “Transdermal Drug Delivery System: Patent Reviews,” Recent Patents on Drug Delivery & Formulation, Vol. 3, No. 2, 2009, pp. 143-152. doi:10.2174/187221109788452294
[5] R. K. Subedi, et al., “Recent Advances in Transdermal Drug Delivery,” Archives of Pharmacal Research, Vol. 33, No. 3, 2010, pp. 339-351. doi:10.1007/s12272-010-0301-7
[6] A. K. Banga, “Microporation Applications for Enhancing Drug Delivery,” Expert Opinion on Drug Delivery, Vol. 6, No. 4, 2009, pp. 343-354. doi:10.1517/17425240902841935
[7] T. R. Singh, et al., “Microporation Techniques for Enhanced Delivery of Therapeutic Agents,” Recent Patents on Drug Delivery & Formulation, Vol. 4, No. 1, 2010, pp. 1-17. doi:10.2174/187221110789957174
[8] V. Sachdeva and A. K. Banga, “Microneedles and Their Applications,” Recent Patents on Drug Delivery & Formulation, Vol. 5, No. 2, 2011, pp. 95-132. doi:10.2174/187221111795471445
[9] J. Birchall, et al., “Cutaneous Gene Expression of Plasmid DNA in Excised Human Skin Following Delivery via Microchannels Created by Radio Frequency Ablation,” International Jour-nal of Pharmaceutics, Vol. 312, No. 1-2, 2006, pp. 15-23. doi:10.1016/j.ijpharm.2005.12.036
[10] N. H. Zech, M. Murtinger and P. Uher, “Pregnancy after Ovarian Superovulation by Transdermal Delivery of Follicle-Stimulating Hormone,” Fertility and Sterility, Vol. 95, No. 8, 2011, pp. 2784-2785. doi: 10.1016/j.fertnstert.2011.03.073
[11] A. V. Badkar, et al., “Transdermal Delivery of Interferon Alpha-2B Using Microporation and Iontophoresis in Hairless Rats,” Pharmaceutical Research, Vol. 24, No. 7, 2007, pp. 1389-1395. doi:10.1007/s11095-007-9308-2
[12] H. Kalluri and A. K. Banga, “Transdermal Delivery of Proteins,” AAPS PharmSciTech, Vol. 12, No. 1, 2011, pp. 431-441. doi:10.1208/s12249-011-9601-6
[13] F. J. McGovern, et al., “Radio Frequency Ablation of Renal Cell Carcinoma via Image Guided Needle Electrodes,” Journal of Urology, Vol. 161, No. 2, 1999, pp. 599-600. doi:10.1016/S0022-5347(01)61961-X
[14] S. N. Gold-berg, “Radiofrequency Tumor Ablation: Principles and Techniques,” European Journal of Ultrasound, Vol. 13, No. 2, 2001, pp. 129-147. doi:10.1016/S0929-8266(01)00126-4
[15] J. H. Park, et al., “The effect of heat on skin permeability,” International Journal of Pharmaceutics, Vol. 359, No. 1-2, 2008, pp. 94-103. doi:10.1016/j.ijpharm.2008.03.032
[16] A. C. Sintov, et al., “Radiofrequency-Driven Skin Microchanneling as a New Way for Electrically Assisted Transdermal Delivery of Hydrophilic Drugs,” Journal of Controlled Release, Vol. 89, No. 2, 2003, pp. 311-320. doi:10.1016/S0168-3659(03)00123-8
[17] G. Levin, et al., “Transdermal Delivery of Human Growth Hormone through RF-Microchannels,” Pharmaceutical Research, Vol. 22, No. 4, 2005, pp. 550-555. doi:10.1007/s11095-005-2498-6
[18] K. Okimoto, R. A. Rajewski and V. J. Stella, “Release of Testosterone from an Osmotic Pump Tablet Utilizing (SBE)7m-Beta-cyclodextrin as Both a Solubilizing and an Osmotic Pump Agent,” Journal of Controlled Release, Vol. 58, No. 1, 1999, pp. 29-38. doi:10.1016/S0168-3659(98)00142-4
[19] J. Pitha, S. M. Harman and M. E. Michel, “Hydrophilic Cyclodextrin Derivatives Enable Effective Oral Administration of Steroidal Hormones,” Journal of Pharmaceutical Sciences, Vol. 75, No. 2, 1986, pp. 165-167. doi:10.1002/jps.2600750213
[20] T. Loftsson, et al., “Effects of Cyclodextrins on Drug Delivery through Biological Membranes,” Journal of Pharmaceutical Sciences, Vol. 96, No. 10, 2007, pp. 2532-2546. doi:10.1002/jps.20992
[21] M. E. Brewster and T. Loftsson, “Cyclodextrins as Pharmaceutical Solubilizers,” Advanced Drug Delivery Reviews, Vol. 59, No. 7, 2007, pp. 645-666. doi:10.1016/j.addr.2007.05.012
[22] H. Kalluri and A. K. Banga, “Formation and Closure of Microchannels in Skin Following Microporation,” Pharmaceutical Research, Vol. 28, No. 1, 2011, pp. 82-94. doi: 10.1007/s11095-010-0122-x
[23] I. Lavon and J. Kost, “Ultrasound and Transdermal Drug Delivery,” Drug Discovery Today, Vol. 9, No. 15, 2004, pp. 670-676. doi:10.1016/S1359-6446(04)03170-8
[24] B. E. Polat, D. Blankschtein and R. Langer, “Low-Frequency Sonophoresis: Application to the Transdermal Delivery of Macromolecules and Hydrophilic Drugs,” Expert Opinion on Drug Delivery, Vol. 7, No. 12, 2010, pp. 1415-1432. doi:10.1517/17425247.2010.538679
[25] K. V. Roskos and R. H. Guy, “Assessment of Skin Barrier Function Using Transepidermal Water Loss: Effect of Age,” Pharmaceutical Research, Vol. 6, No. 11, 1989, pp. 949-953. doi:10.1023/A:1015941412620
[26] G. Grubauer, P. M. Elias and K. R. Feingold, “Transepider-mal Water Loss: The Signal for Recovery of Barrier Structure and Function,” Journal of Lipid Research, Vol. 30, No. 3, 1989, pp. 323-333.
[27] A. Anigbogu, et al., “An in Vivo Investigation of the Rabbit Skin Responses to Transdermal Iontophoresis,” International Journal of Pharmaceutics, Vol. 200, No. 2, 2000, pp. 195-206. doi:10.1016/S0378-5173(00)00371-9
[28] F. W. Benech-Kieffer and H. Schaefer, “Transepidermal Water Loss as an Integrity Test for Skin Barrier Function in Vitro: Assay Standardization,” In: K. R. Brain, V. J. James and K. A. Walters, Eds., Perspectives in Percutaneous Penetration, STS Publishing, Cardiff, 1977, p. 56.
[29] FDA Wound Healing Clinical Focus Group, “Guidance for Industry: Chronic Cutaneous Ulcer and Burn Wounds- Developing Products for Treatment,” Wound Repair and Regeneration, Vol. 9, No. 4, 2001, pp. 258-268. doi:10.1046/j.1524-475X.2001.00258.x
[30] R. Panchagnula, K. Stemmer and W. A. Ritschel, “Animal Models for Transdermal Drug Delivery,” Methods & Findings in Experimental & Clinical Pharmacology, Vol. 19, No. 5, 1997, pp. 335-341.
[31] R. F. Diegelmann and M. C. Evans, “Wound Healing: An Overview of Acute, Fibrotic and Delayed Healing,” Frontiers in Bioscience, Vol. 9, 2004, pp. 283-289. doi:10.2741/1184
[32] D. Montandon, G. D’Andiran and G. Gabbiani, “The Mechanism of Wound Contraction and Epithelialization: Clinical and Experimental Studies,” Clinics in Plastic Surgery, Vol. 4, No. 3, 1977, pp. 325-346.
[33] J. Gupta, et al., “Kinetics of Skin Resealing after Insertion of Microneedles in Human Subjects,” Journal of Controlled Release, Vol. 154, No. 2, 2011, pp. 148-155. doi:10.1016/j.jconrel.2011.05.021

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