Advances in Radio-Frequency Transdermal Drug Delivery - Pharmaceutical Technology

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Advances in Radio-Frequency Transdermal Drug Delivery
A microelectronic system based on radio-frequency (RF) cell ablation addresses limitations of other transdermal drug-delivery methods. This system expands the transdermal spectrum to include the delivery of water-soluble molecules, peptides, proteins, and other macromolecules.


Pharmaceutical Technology


Iontophoresis. Iontophoresis is another transdermal delivery option. This approach uses an electrical repulsion of a relatively low voltage to drive molecules through the intact skin. Iontophoresis is successful only with drug molecules of up to 1000 Da. Because delivery through the intact skin requires formulations of certain pH levels, the target drug needs to be ionized for successful delivery. Iontophoresis can only be applied for short periods of time because of possible skin irritation caused by the electrical current. Only drugs with short-delivery duration, therefore, can be used with this technology. Delivery by RF cell ablation is not limited by these factors. There is no molecular size limitation, no molecular electrical charge requirement, and no specific formulation pH constraint.

Microneedles. Microneedles represent another transdermal delivery option. Microneedles create a matrix of holes in the skin using an array of ultra-sharp microscopic needles; however, they too suffer from significant limitations. The amount of drug that can be coated on microneedles is limited, so only very potent drugs are suitable for this technology. In addition, a complex formulation is needed to enable the drug to be efficiently coated onto the microneedles. Delivery through microneedles results in a sharp peak profile, compared with the more extended release the delivery system based on RF-cell ablation.

Conclusion

A microelectronic system based on radio-frequency cell ablation may be used in various therapeutic applications. Such a system can be a transdermal delivery solution for polypeptides, other large molecules, and water-soluble small molecules. This system also allows enhanced immunizations by providing a painless, safe, and effective alternative to current intramuscular or subcutaneous vaccination methods. RF microchannels also improve penetration of the drug substance and dosage control.

Galit Levin, DSc, is vice-president of pharmaceutical research and development at TransPharma Medical Ltd., 2 Yodfat St. Northern Industrial Zone, Lod, Israel 71291, tel. 972.8.915.2201, fax 972.8.915.2202,

References

1. B. Decadt and A.K. Siriwardena, "Radiofrequency Ablation of Liver Tumors: A Systematic Review," Lancet Oncol. 5 (9), 550–560 (2004).

2. A. Hines-Peralta and S.N. Goldberg, "Review of Radiofrequency Ablation for Renal Cell Carcinoma," Clin. Cancer Res. 10 , 6328S–6334S (2004).

3. S. Nahum Goldberg, "Radiofrequency Tumor Ablation: Principles and Techniques," Eur. J. Ultrasound 13 (2), 129–147 (2001).

4. L. Solbiati et al., "Radiofrequency Thermal Ablation of Hepatic Metastases," Eur. J. Ultrasound, 13 (2), 149–158 (2001).

5. F.J. McGovern et al., "Radiofrequency Ablation of Renal Cell Carcinoma via Image Guided Needle Electrodes," J. Urol. 161 (2), 599–600 (1999).

6. A.S. Sintov et al., "Radiofrequency-driven Skin Microchanneling as a New Way for Electrically Assisted Transdermal Delivery of Hydrophilic Drugs," J. Controlled Release, 89 (2), 311–320 (2003).

7. Z. Avrahami, "Transdermal Drug Delivery and Analyte Extraction," US Patent No. 6,148,232 (2000).

8. Z. Sohn and Z. Avrahami, "Monopolar and Bipolar Current Application for Transdermal Drug Delivery and Analyte Extraction," US Patent No. 6,611,706 (2001).

9. G. Levin et al., "Transdermal Delivery of Human Growth Hormone through RF-Microchannels," Pharm. Res. 22 (4), 550–555 (2005).

10. M.R. Prausnitz, S. Mitragotri, and L. Langer, "Current Status and Future Potential of Transdermal Drug Delivery," Nature Rev. Drug Disc. 3 (2),115–124 (2004).

11. G. Levin et al., "ViaDerm, A Novel Microelectronic System Enables Skin Permeability of Drugs: In-vitro and In-vivo Percutaneous Delivery of Macromolecules," presented at the Ninth International Conference, Perspectives in Percutaneous Penetration, La Grande Motte, France, 2004.

12. J.L. Cleland, A. Daugherty, and R. Mrsny "Emerging Protein Delivery Methods, Curr. Opin. Biotechnol. 12 (2) 212–219 (2001).


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