Transdermal delivery of biologics using microneedle-array (MNA) based devices offers attractive theoretical advantages over prevailing oral and needle-based drug delivery methods. However, considerable practical limitations in design, fabrication, and testing are preventing the discovery of clinically relevant array designs. The goal of this project is to rationally design a cutaneous delivery platform based on a dissolvable microneedle array that enables efficient, precise, and reproducible delivery of biologically active molecules to human skin. Importantly, we propose to accomplish this with a microneedle array delivery platform that is directly applicable to patient-friendly, clinical delivery of a broad range of therapeutic agents. We have assembled a multi-disciplinary team of investigators with broad and directly relevant experience in mechanical engineering, cutaneous biology, and dermatology. Together we have developed novel and comprehensive micro-milling based fabrication technologies that uniquely position us to accomplish this goal. Through studies proposed here, we will identify geometric and mechanical properties of microneedle and array configurations that impact the effectiveness and reproducibility of MNA drug delivery. This new knowledge will be applied to the design and fabrication of MNAs with physical characteristics compatible with effective intracutaneous drug delivery.

Public Health Relevance

Transdermal delivery of biologics using microneedle-array (MNA) based devices offers attractive theoretical advantages over prevailing oral and needle-based drug delivery methods. However, considerable practical limitations in design, fabrication, and testing are preventing the discovery of clinically relevant array designs. The goal of this project is to rationally design a cutaneous delivery platform based on a dissolvable microneedle array that enables efficient, precise, and reproducible delivery of biologically active molecules to human skin. Importantly, we propose to accomplish this with a microneedle array delivery platform that is directly applicable to patient-friendly, clinical delivery of a broad range of therapeutic agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB012776-01
Application #
8033549
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Zullo, Steven J
Project Start
2010-09-30
Project End
2014-08-31
Budget Start
2010-09-30
Budget End
2011-08-31
Support Year
1
Fiscal Year
2010
Total Cost
$447,629
Indirect Cost
Name
University of Pittsburgh
Department
Dermatology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Balmert, Stephen C; Donahue, Cara; Vu, John R et al. (2017) In vivo induction of regulatory T cells promotes allergen tolerance and suppresses allergic contact dermatitis. J Control Release 261:223-233
Korkmaz, Emrullah; Friedrich, Emily E; Ramadan, Mohamed H et al. (2015) Therapeutic intradermal delivery of tumor necrosis factor-alpha antibodies using tip-loaded dissolvable microneedle arrays. Acta Biomater 24:96-105
Zhang, Yi; Chen, Guo; Liu, Zuqiang et al. (2015) Genetic vaccines to potentiate the effective CD103+ dendritic cell-mediated cross-priming of antitumor immunity. J Immunol 194:5937-47
Bediz, Bekir; Korkmaz, Emrullah; Khilwani, Rakesh et al. (2014) Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application. Pharm Res 31:117-35