Skip to main content

Advertisement

SpringerLink
Log in

Transdermal delivery of human growth hormone via laser-generated micropores

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

The epidermal skin barrier plays an important role in protecting underlying structures. It allows the passage of low molecular weight lipophilic molecules, but restricts the passage of hydrophilic molecules and macromolecules. The objective of this study was to investigate the feasibility of transdermal delivery of human growth hormone (hGH) through laser-microporated dermatomed porcine ear skin. The permeation of hGH was evaluated at different laser fluences and micropore densities. In vitro permeation studies were performed on vertical Franz diffusion cells using dermatomed porcine ear skin treated with ablative laser (2940 nm; P.L.E.A.S.E®, Pantec Biosolutions AG). The effect of different fluences (34.1, 45.4, and 68.1 J/cm2) at 10% pore density as well as different densities of micropores (5, 10, and 15%) at fluence of 34.1 J/cm2, on the permeation of hGH was evaluated. After 48 h, 77.12 ± 10.77 μg/cm2 hGH was delivered into the receptor with the application of fluence of 45.4 J/cm2, which was significantly higher than that observed from 34.1 J/cm2 group (53.13 ± 1.75 μg/cm2, p < 0.05). Application of fluence of 68.1 J/cm2 showed permeation of 90.94 ± 3.93 μg/cm2 that was significantly higher than that from 34.1 J/cm2 group (p < 0.05), but not as compared to the 45.4 J/cm2 group (p > 0.05). With the increase in density of micropores from 5 to 15%, permeation of hGH increased significantly from 7.1 ± 2.63 μg/cm2 to 95.89 ± 13.43 μg/cm2 after 48 h (p < 0.05). Thus, overall, the variations in the fluence as well as micropore density of the laser were observed to influence hGH permeation, through laser-microporated dermatomed porcine skin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

ANOVA:

Analysis of variance

ELISA:

Enzyme-linked immunosorbent assay

hGH:

Human growth hormone

P.L.E.A.S.E®:

Precise Laser Epidermal System

References

  1. Strobl JS, Thomas MJ. Human growth hormone. Pharmacol Rev. 1994;46:1–34.

    CAS  PubMed  Google Scholar 

  2. Cai Y, Xu M, Yuan M, Liu Z, Yuan W. Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes. Int J Nanomedicine. 2014;9:3527–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Rogol AD. Growth hormone and the adolescent athlete: what are the data for its safety and efficacy as an ergogenic agent? Growth Hormon IGF Res. 2009;19:294–9.

    Article  CAS  Google Scholar 

  4. Bartke A. Growth hormone and aging: a challenging controversy. Clin Interv Aging. 2008;3:659–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Takano K, Shizume K, Hibi I. A comparison of subcutaneous and intramuscular administration of human growth hormone (hGH) and increased growth rate by daily injection of hGH in GH deficient children. Endocrinol Jpn. 1988;35:477–84.

    Article  CAS  PubMed  Google Scholar 

  6. Levin G, Gershonowitz A, Sacks H, Stern M, Sherman A, Rudaev S, et al. Transdermal delivery of human growth hormone through RF-microchannels. Pharm Res. 2005;22:550–5.

    Article  CAS  PubMed  Google Scholar 

  7. Banga AK. Transdermal and intradermal delivery of therapeutic agents: application of physical technologies: CRC Press; 2011.

  8. Pubchem. Human growth hormone (32–38) | C39H60N8O13 - PubChem [Internet]. [cited 2017]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/126658

  9. Hessenberger M, Weiss R, Weinberger EE, Boehler C, Thalhamer J, Scheiblhofer S. Transcutaneous delivery of CpG-adjuvanted allergen via laser-generated micropores. Vaccine. 2013;31:3427–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Terhorst D, Fossum E, Baranska A, Tamoutounour S, Malosse C, Garbani M, et al. Laser-assisted intradermal delivery of adjuvant-free vaccines targeting XCR1+ dendritic cells induces potent antitumoral responses. J Immunol. 2015;194:5895–902.

    Article  CAS  PubMed  Google Scholar 

  11. Weiss R, Hessenberger M, Kitzmüller S, Bach D, Weinberger EE, Krautgartner WD, et al. Transcutaneous vaccination via laser microporation. J Control Release. 2012;162:391–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ganti SS, Banga AK. Non-ablative fractional laser to facilitate transdermal delivery. J Pharm Sci. 2016;105:3324–32.

    Article  CAS  PubMed  Google Scholar 

  13. Lee W-R, Shen S-C, Al-Suwayeh SA, Yang H-H, Yuan C-Y, Fang J-Y. Laser-assisted topical drug delivery by using a low-fluence fractional laser: imiquimod and macromolecules. J Control Release. 2011;153:240–8.

    Article  CAS  PubMed  Google Scholar 

  14. Brunner M, Dehghanyar P, Seigfried B, Martin W, Menke G, Müller M. Favourable dermal penetration of diclofenac after administration to the skin using a novel spray gel formulation. Br J Clin Pharmacol. 2005;60:573–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Miyatake S, Ichiyama H, Kondo E, Yasuda K. Randomized clinical comparisons of diclofenac concentration in the soft tissues and blood plasma between topical and oral applications. Br J Clin Pharmacol. 2009;67:125–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lee W-R, Shen S-C, Liu C-R, Fang C-L, Hu C-H, Fang J-Y. Erbium:YAG laser-mediated oligonucleotide and DNA delivery via the skin: an animal study. J Control Release. 2006;115:344–53.

    Article  CAS  PubMed  Google Scholar 

  17. Gómez C, Costela Á, García-Moreno I, Llanes F, Teijón JM, Blanco MD. Skin laser treatments enhancing transdermal delivery of ALA. J Pharm Sci. 2011;100:223–31.

    Article  PubMed  Google Scholar 

  18. Bachhav YG, Summer S, Heinrich A, Bragagna T, Böhler C, Kalia YN. Effect of controlled laser microporation on drug transport kinetics into and across the skin. J Control Release. 2010;146:31–6.

    Article  CAS  PubMed  Google Scholar 

  19. Bach D, Weiss R, Hessenberger M, Kitzmueller S, Weinberger EE, Krautgartner WD, et al. Transcutaneous immunotherapy via laser-generated micropores efficiently alleviates allergic asthma in Phl p 5–sensitized mice. Allergy. 2012;67:1365–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chen X, Shah D, Kositratna G, Manstein D, Anderson RR, Wu MX. Facilitation of transcutaneous drug delivery and vaccine immunization by a safe laser technology. J Control Release. 2012;159:43–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nguyen HX, Banga AK. Enhanced skin delivery of vismodegib by microneedle treatment. Drug Deliv Transl Res. 2015;5:407–23.

    Article  CAS  PubMed  Google Scholar 

  22. Sachdeva V, Zhou Y, Banga AK. In vivo transdermal delivery of leuprolide using microneedles and iontophoresis. Curr Pharm Biotechnol. 2013;14:180–93.

    CAS  PubMed  Google Scholar 

  23. Puri A, Nguyen HX, Banga AK. Microneedle-mediated intradermal delivery of epigallocatechin-3-gallate. Int J Cosmet Sci. 2016;38:512–23.

    Article  CAS  PubMed  Google Scholar 

  24. Davies DJ, Ward RJ, Heylings JR. Multi-species assessment of electrical resistance as a skin integrity marker for in vitro percutaneous absorption studies. Toxicol Vitro. 2004;18:351–8.

    Article  CAS  Google Scholar 

  25. Shaji J, Varkey D. Recent advances in physical approaches for transdermal penetration enhancement. Curr Drug Ther. 2012;7:184–97.

    Article  CAS  Google Scholar 

  26. Ruan R, Chen M, Zou L, Wei P, Liu J, Ding W, et al. Recent advances in peptides for enhancing transdermal macromolecular drug delivery. Ther Deliv. 2016;7:89–100.

    Article  CAS  PubMed  Google Scholar 

  27. Bachhav YG, Heinrich A, Kalia YN. Controlled intra- and transdermal protein delivery using a minimally invasive Erbium:YAG fractional laser ablation technology. Eur J Pharm Biopharm. 2013;84:355–64.

    Article  CAS  PubMed  Google Scholar 

  28. Oni G, Brown SA, Kenkel JM. Can fractional lasers enhance transdermal absorption of topical lidocaine in an in vivo animal model? Lasers Surg Med. 2012;44:168–74.

    Article  PubMed  Google Scholar 

  29. Bachhav YG, Heinrich A, Kalia YN. Using laser microporation to improve transdermal delivery of diclofenac: increasing bioavailability and the range of therapeutic applications. Eur J Pharm Biopharm. 2011;78:408–14.

    Article  CAS  PubMed  Google Scholar 

  30. Dick IP, Scott RC. Pig ear skin as an in-vitro model for human skin permeability. J Pharm Pharmacol. 1992;44:640–5.

    Article  CAS  PubMed  Google Scholar 

  31. Jacobi U, Kaiser M, Toll R, Mangelsdorf S, Audring H, Otberg N, et al. Porcine ear skin: an in vitro model for human skin. Skin Res Technol. 2007;13:19–24.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, 30341, USA

    Yang Song, Ashana Puri & Ajay K. Banga

  2. Luminance Clinic, Mumbai, India

    Karishma Hemmady

Authors
  1. Yang Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karishma Hemmady
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashana Puri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ajay K. Banga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ajay K. Banga.

Ethics declarations

Conflict of interests

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, Y., Hemmady, K., Puri, A. et al. Transdermal delivery of human growth hormone via laser-generated micropores. Drug Deliv. and Transl. Res. 8, 450–460 (2018). https://doi.org/10.1007/s13346-017-0370-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-017-0370-y

Keywords

Search

Navigation