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Transdermal Delivery of Macromolecules Using Solid-State Biodegradable Microstructures

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ABSTRACT

Purpose

The purpose of this work is to demonstrate the feasibility of using a proprietary technology called MicroCor™, based on solid-state, biodegradable microstructures (SSBMS), for transdermal delivery of macromolecules.

Methods

The proteins FITC-BSA (66 kDa) and recombinant protective antigen (rPA; 83 kDa) were incorporated into SSBMS arrays using a mold-based, liquid formulation casting and drying process. Arrays were applied to the skin with a custom applicator and then inspected to assess the extent of microstructure dissolution. In vitro FITC-BSA delivery to human cadaver skin was visualized using light and fluorescence microscopy and quantified by extracting and measuring the fluorescently labeled protein. rPA-containing SSBMS arrays were applied in vivo to Sprague-Dawley rats. The resulting serum IgG response was measured by ELISA and compared with responses elicited from intramuscular (IM) and intradermal (ID) routes of administration.

Results

FITC-BSA and rPA SSBMS arrays successfully penetrated the skin. Microstructure dissolution was observed over >95% of the array area and >75% of the microstructure length. FITC-BSA delivery correlated with protein content in the formulations. Antibody titers after transdermal delivery of rPA were comparable or higher than IM and ID titers.

Conclusions

Transdermal delivery of macromolecules can be conveniently and effectively accomplished using the MicroCor technology.

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Abbreviations

SSBMS:

solid-state biodegradable microstructures

FITC-BSA:

fluorescein isothiocyanate—bovine serum albumin

rPA:

recombinant protective antigen (ex. Bacillus anthracis)

ID:

intradermal

IM:

intramuscular

IgG:

immunoglobulin G

PET:

polyethylene terephthalate

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ACKNOWLEDGMENTS

The authors would like to acknowledge Appala Sagi, Danir Bairamov, Mikhail Shapiro, Creag Trautman, and Wade Worsham of Corium International, Inc. for fabrication of the SSBMS arrays and design of the custom impactor device. The authors would also like to gratefully acknowledge Raymond Daynes of the University of Utah for helpful discussions and technical assistance with executing the immunization studies.

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Authors and Affiliations

  1. Corium International, Inc., 235 Constitution Drive, Menlo Park, California, 94025, USA

    Janet R. Wendorf, Esi B. Ghartey-Tagoe, Stephen C. Williams, Parminder Singh & Gary W. Cleary

  2. Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, 84132, USA

    Elena Enioutina

Authors
  1. Janet R. Wendorf
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  2. Esi B. Ghartey-Tagoe
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  3. Stephen C. Williams
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  4. Elena Enioutina
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  5. Parminder Singh
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  6. Gary W. Cleary
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Corresponding author

Correspondence to Gary W. Cleary.

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Wendorf, J.R., Ghartey-Tagoe, E.B., Williams, S.C. et al. Transdermal Delivery of Macromolecules Using Solid-State Biodegradable Microstructures. Pharm Res 28, 22–30 (2011). https://doi.org/10.1007/s11095-010-0174-y

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  • DOI: https://doi.org/10.1007/s11095-010-0174-y

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