No Heading
Purpose.
To evaluate the bioavailability and bioactivity of human growth hormone (hGH) delivered transdermally through microchannels (MCs) in the skin created by radio-frequency (RF) ablation.
Methods.
The creation of MCs was observed in magnified rat and guinea pig skin after staining by methylene blue. Various doses of hGH in a dry form were applied on rat or guinea pig (GP) skin after the formation of MCs. The pharmacokinetic profile of systemic hGH in both animal models was monitored for 15 h post patch application. Bioactivity of the transdermally delivered hGH was verified by measuring IGF-I levels in hypophysectomized rats.
Results.
The ordered array of MCs was clearly visible in the magnified rat and guinea pig skin. The MCs were very uniform in diameter and of equal separation. Creation of MCs in the outer layers of the skin enabled efficient delivery of hGH, with a bioavailability of 75% (rats) or 33% (GPs) relative to subcutaneous (s.c.) injection with plasma profiles resembling that of s.c. injection. Elevated levels of systemic insulin-like growth factor-1 (IGF-I) were observed after transdermal delivery of hGH to hypophysectomized rats indicative of the bioactivity of the transdermally delivered hGH in vivo.
Conclusions.
Formation of RF-microchannels is a well-controlled process. These MCs permitted the transdermal delivery of bioactive hGH in rats and GPs with high bioavailability.
Similar content being viewed by others
References
1. R. R. B. Shah, F. Ahsan, and M. A. Khan. Oral delivery of proteins: progress and prognostication. Crit. Rev. Ther. Drug Carrier Syst. 19:135–169 (2002).
2. A. P. Sayani and Y. W. Chien. Systemic delivery of peptides and proteins across absorptive mucosae Crit. Rev. Ther. Drug Carrier Syst. 13:85–184 (1996).
3. R. U. Agu, M. I. Ugwoke, M. Armand, R. Kinget, and N. Verbeke. The lung as a route for systemic delivery of therapeutic proteins and peptides Respir. Res. 2:198–209 (2001).
4. J. L. Cleland, A. Daugherty, and R. Mrsny. Emerging protein delivery methods. Curr. Opin. Biotechnol. 12212–219 (2001).
5. S. N. Goldberg. Radiofrequency tumor ablation: principles and techniques Eur. J. Ultrasound 13:129–147 (2001).
6. L. Solbiati, T. Ierace, M. Tonolini, V. Osti, and L. Cova. Radiofrequency thermal ablation of hepatic metastases. Eur. J. Ultrasound 13149–158 (2001).
7. F. J. McGovern, B. J. Wood, S. N. Goldberg, and P. R. Mueller. Radiofrequency ablation of renal cell carcinoma via image guided needle electrodes. J. Urol. 161:599–600 (1999).
8. F. Izzo, C. C. Barnett, and S. A. Curley. Radiofrequency ablation of primary and metastatic malignant liver tumors. Adv. Surg. 35:225–250 (2001).
9. A. C. Sintov, I. Krymberk, D. Daniel, T. Hannan, Z. Sohn, and G. Levin. Radiofrequency-driven skin microchanneling as a new way for electrically assisted transdermal delivery of hydrophilic drugs J. Control. Release 89:311–320 (2003).
10. B. L. Silverman, S. L. Blethen, E. O. Reiter, K. M. Attie, R. B. Neuwirth, and K. M. Ford. A long-acting human growth hormone (Nutropin depot): efficacy and safety following two years of treatment in children with growth hormone deficiency. J. Pediatr. Endocrinol. Metab. 15:715–722 (2002).
11. International Patent Application WO 2004/039428. Transdermal delivery system for dried particulate or lyophilized medications, TransPharma Medical Ltd., Lod, Israel.
12. M. Phillip, G. Maor, S. Assa, A. Silbergeld, and Y. Segev. Testosterone stimulates growth of tibial epiphyseal growth plate and insulin-like growth factor-1 receptor abundance in hypophysectomized and castrated rats. Endocrine 16:1–6 (2001).
13. N. Kankikkannan. Iontophoresis-based transdermal delivery systems BioDrugs 16:339–347 (2002).
14. B. W. Barry. Novel mechanisms and devices to enable successful transdermal drug delivery Eur. J. Pharm. Sci. 14:101–114 (2001).
15. G. L. Grove, M. J. Grove, C. Zerweck, and E. Pierce. Comparative metrology of the evaporimeter and the Dermalab TEWL probe Skin Res. Technol. 5:1–8 (1999).
16. R. Panchagnula, K. Stemmer, and W. A. Ritschel. Animal models for transdermal delivery Meth. Find. Exp. Clin. Pharmacol. 19:335–341 (1997).
17. A. Rougier, C. Lotte, and H. I. Maibach. In vivo relationship between percutaneous absorption and transepidermal water loss. In: R. L. Bronaugh and H. I. Maibach (eds.), Percutaneous Absorption, Marcel Dekker, New York, 1999, pp. 117–132.
18. V. R. Sinha and M. P. Kaur. Permeation enhancers for transdermal drug delivery. Drug Dev. Ind. Pharm. 26:1131–1140 (2000).
19. W. V. J. Wilson, M. Rattray, C. R. Thomas, B. H. Moreland, and D. Schulster. Effects of hypophysectomy and growth hormone administration on the mRNA levels of collagen I,III and insulin-like growth factor-I in rat skeletal muscle. Growth Horm. IGF Res. 8:431–438 (1998).
20. J. Oscarsson, M. Ottosson, K. Vikman-Adolfsson, F. Frick, S. Enerback, H. Lithell, and S. Eden. GH but not IGF-I or insulin increases lipoprotein lipase activity in muscle tissues of hypophysectomised rats J. Endocrinol. 160:247–255 (1999).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Levin, G., Gershonowitz, A., Sacks, H. et al. Transdermal Delivery of Human Growth Hormone Through RF-Microchannels. Pharm Res 22, 550–555 (2005). https://doi.org/10.1007/s11095-005-2498-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-005-2498-6