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Formation and Closure of Microchannels in Skin Following Microporation

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ABSTRACT

Purpose

To characterize the microchannels created in hairless rat skin by microneedles and investigate their closure following exposure to different occlusive conditions.

Methods

Maltose microneedles were characterized by scanning electron microscopy. The microchannels created and their closure when exposed to different conditions was investigated using a variety of techniques.

Results

Microscopic imaging indicates a pyramidal geometry of maltose microneedles with an average length of 559 ± 14 μm and tip radius of 4 μm. Upon insertion into skin, they created microchannels with an average surface diameter of 60 μm and an average depth of 160 ± 20 μm as observed by histological sectioning and confocal microscopy. Skin recovers its barrier function within 3–4 hrs, and microchannels closed within 15 hrs of poration when exposed to environment. However, when occluded, the microchannels remained open for up to 72 hrs in vivo, as observed by calcein imaging, transepidermal water loss measurements and methylene blue staining.

Conclusion

Maltose microneedles penetrated the stratum corneum barrier and created microchannels in skin which completely close within 15 hrs after poration. However, under occluded conditions, barrier recovery can be delayed for up to 72 hrs in vivo.

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REFERENCES

  1. Banga AK. Microporation applications for enhancing drug delivery. Expert Opin Drug Deliv. 2009;6:343–54.

    Article  CAS  PubMed  Google Scholar 

  2. Kolli CS, Banga AK. Characterization of solid maltose microneedles and their use for transdermal delivery. Pharm Res. 2008;25:104–13.

    Article  CAS  PubMed  Google Scholar 

  3. Cormier M, Johnson B, Ameri M, Nyam K, Libiran L, Zhang DD et al. Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Release. 2004;97:503–11.

    CAS  PubMed  Google Scholar 

  4. Martanto W, Davis SP, Holiday NR, Wang J, Gill HS, Prausnitz MR. Transdermal delivery of insulin using microneedles in vivo. Pharm Res. 2004;21:947–52.

    Article  CAS  PubMed  Google Scholar 

  5. Davis SP, Martanto W, Allen MG, Prausnitz MR. Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans Biomed Eng. 2005;52:909–15.

    Article  PubMed  Google Scholar 

  6. Park JH, Allen MG, Prausnitz MR. Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J Control Release. 2005;104:51–66.

    Article  CAS  PubMed  Google Scholar 

  7. Matriano JA, Cormier M, Johnson J, Young WA, Buttery M, Nyam K et al. Macroflux microprojection array patch technology: a new and efficient approach for intracutaneous immunization. Pharm Res. 2002;19:63–70.

    Article  CAS  PubMed  Google Scholar 

  8. Lin W, Cormier M, Samiee A, Griffin A, Johnson B, Teng CL et al. Transdermal delivery of antisense oligonucleotides with microprojection patch (Macroflux) technology. Pharm Res. 2001;18:1789–93.

    Article  CAS  PubMed  Google Scholar 

  9. Chabri F, Bouris K, Jones T, Barrow D, Hann A, Allender C et al. Microfabricated silicon microneedles for nonviral cutaneous gene delivery. Br J Dermatol. 2004;150:869–77.

    Article  CAS  PubMed  Google Scholar 

  10. McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci USA. 2003;100:13755–60.

    Article  CAS  PubMed  Google Scholar 

  11. Li G, Badkar A, Nema S, Kolli CS, Banga AK. In vitro transdermal delivery of therapeutic antibodies using maltose microneedles. Int J Pharm. 2009;368:109–15.

    Article  CAS  PubMed  Google Scholar 

  12. Widera G, Johnson J, Kim L, Libiran L, Nyam K, Daddona PE et al. Effect of delivery parameters on immunization to ovalbumin following intracutaneous administration by a coated microneedle array patch system. Vaccine. 2006;24:1653–64.

    Article  CAS  PubMed  Google Scholar 

  13. Teo MAL, Shearwood C, Ng KC, Lu J, Moochhala S. In vitro and in vivo characterization of MEMS microneedles. Biomed Microdevices. 2005;7:47–52.

    Article  PubMed  Google Scholar 

  14. Wang PM, Cornwell M, Hill J, Prausnitz MR. Precise microinjection into skin using hollow microneedles. J Invest Dermatol. 2006;126:1080–7.

    Article  CAS  PubMed  Google Scholar 

  15. Kalluri H, Banga AK. Microneedles and transdermal drug delivery. Journal of drug delivery science and technology. In print: 2009.

  16. Teo AL, Shearwood C, Ng KC, Lu J, Moochhala S. Transdermal microneedles for drug delivery applications. Mater Sci Eng B. 2006.

  17. Oh JH, Park HH, Do KY, Han M, Hyun DH, Kim CG et al. Influence of the delivery systems using a microneedle array on the permeation of a hydrophilic molecule, calcein. Eur J Pharm Biopharm. 2008;69:1040–5.

    Article  CAS  PubMed  Google Scholar 

  18. Mikszta JA, Alarcon JB, Brittingham JM, Sutter DE, Pettis RJ, Harvey NG. Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery. Nat Med. 2002;8:415–9.

    Article  CAS  PubMed  Google Scholar 

  19. Menon GK, Feingold KR, Elias PM. Lamellar body secretory response to barrier disruption. J Invest Dermatol. 1992;98:279–89.

    Article  CAS  PubMed  Google Scholar 

  20. Elias PM. Epidermal lipids, barrier function, and desquamation. J Invest Dermatol. 1983;80(Suppl):44s–9.

    Article  CAS  Google Scholar 

  21. Al-Qallaf B, Das DB. Optimizing microneedle arrays for transdermal drug delivery: extension to non-square distribution of microneedles. J Drug Target. 2009;17:108–22.

    Article  CAS  PubMed  Google Scholar 

  22. Gupta J. Microneedles for transdermal drug delivery in human subjects, School of Chemical and Biomolecular Engineering, Vol. Ph.D. Dissertation, Georgia Institute of Technology, Atlanta; 2009. p. 198.

  23. Gupta J, Andrews S, Gill HS, Prausnitz MR. Kinetics of skin resealing after insertion of microneedles in human subjects. New York: Controlled Release Society Annual Meeting; 2008.

    Google Scholar 

  24. Haq MI, Smith E, John DN, Kalavala M, Edwards C, Anstey A et al. Clinical administration of microneedles: skin puncture, pain and sensation. Biomed Microdevices. 2009;11:35–47.

    Article  CAS  PubMed  Google Scholar 

  25. Al-Qallaf B, Das DB. Optimizing microneedle arrays to increase skin permeability for transdermal drug delivery. Ann N Y Acad Sci. 2009;1161:83–94.

    Article  PubMed  Google Scholar 

  26. Grubauer G, Elias PM, Feingold KR. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res. 1989;30:323–33.

    CAS  PubMed  Google Scholar 

  27. Ahn SK, Jiang SJ, Hwang SM, Choi EH, Lee JS, Lee SH. Functional and structural changes of the epidermal barrier induced by various types of insults in hairless mice. Arch Dermatol Res. 2001;293:308–18.

    Article  CAS  PubMed  Google Scholar 

  28. Kennish L, Reidenberg B. A review of the effect of occlusive dressings on lamellar bodies in the stratum corneum and relevance to transdermal absorption. Dermatol Online J. 2005;11:7.

    PubMed  Google Scholar 

  29. Menon GK, Elias PM, Feingold KR. Integrity of the permeability barrier is crucial for maintenance of the epidermal calcium gradient. Br J Dermatol. 1994;130:139–47.

    Article  CAS  PubMed  Google Scholar 

  30. Menon GK, Grayson S, Elias PM. Ionic calcium reservoirs in mammalian epidermis: ultrastructural localization by ion-capture cytochemistry. J Invest Dermatol. 1985;84:508–12.

    Article  CAS  PubMed  Google Scholar 

  31. Taljebini M, Warren R, Mao-Oiang M, Lane E, Elias PM, Feingold KR. Cutaneous permeability barrier repair following various types of insults: kinetics and effects of occlusion. Skin Pharmacol. 1996;9:111–9.

    Article  CAS  PubMed  Google Scholar 

  32. Jiang S, Koo SW, Lee SH. The morphologic changes in lamellar bodies and intercorneocyte lipids after tape stripping and occlusion with a water vapor-impermeable membrane. Arch Dermatol Res. 1998;290:145–51.

    Article  CAS  PubMed  Google Scholar 

  33. Mao-Qiang M, Mauro T, Bench G, Warren R, Elias PM, Feingold KR. Calcium and potassium inhibit barrier recovery after disruption, independent of the type of insult in hairless mice. Exp Dermatol. 1997;6:36–40.

    Article  CAS  PubMed  Google Scholar 

  34. Lee SH, Elias PM, Proksch E, Menon GK, Mao-Quiang M, Feingold KR. Calcium and potassium are important regulators of barrier homeostasis in murine epidermis. J Clin Invest. 1992;89:530–8.

    Article  CAS  PubMed  Google Scholar 

  35. Lee SH, Elias PM, Feingold KR, Mauro T. A role for ions in barrier recovery after acute perturbation. J Invest Dermatol. 1994;102:976–9.

    Article  CAS  PubMed  Google Scholar 

  36. Hachem JP, Crumrine D, Fluhr J, Brown BE, Feingold KR, Elias PM. pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. J Invest Dermatol. 2003;121(2):345–53.

    Google Scholar 

  37. Fluhr JW, Mao-Qiang M, Brown BE, Hachem JP, Moskowitz DG, Demerjian M, Haftek M, Serre G, Crumrine D, Mauro TM, Elias PM, Feingold KR. Functional consequences of a neutral pH in neonatal rat stratum corneum. J Invest Dermatol. 2004;123(1):140–50.

    Google Scholar 

  38. Hachem JP, Man MQ, Crumrine D, Uchida Y, Brown BE, Rogiers V, Roseeuw D, Feingold KR, Elias PM. Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. J Invest Dermatol. 2005;125(3):510–20.

    Google Scholar 

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ACKNOWLEDGEMENTS

The authors would like to thank Dr. Chandrasekhar Kolli and David Farquhar for help with calcein imaging studies.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, 3001 Mercer University Drive, Atlanta, Georgia, 30341, USA

    Haripriya Kalluri & Ajay K. Banga

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  1. Haripriya Kalluri
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  2. Ajay K. Banga
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Correspondence to Ajay K. Banga.

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Kalluri, H., Banga, A.K. Formation and Closure of Microchannels in Skin Following Microporation. Pharm Res 28, 82–94 (2011). https://doi.org/10.1007/s11095-010-0122-x

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  • DOI: https://doi.org/10.1007/s11095-010-0122-x

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