One of the greatest challenges in drug delivery is the administration of macromolecules across the skin at therapeutic rates. This proposal describes the use of microscopic needles which are long enough to deliver drugs across the skin's outer layer of stratum corneum, but are short enough to avoid hitting nerves and thereby avoid causing pain. Preliminary studies show that arrays of microneedles can be etched from silicon using the same microfabrication technology used to made integrated circuits. These arrays have been shown to increase skin permeability in vitro by up to five orders of magnitude for small molecules (calcein), macromolecules (insulin, bovine serum albumin) and nanospheres (100 nm diameter). Preliminary human studies indicate that microneedles inserted into the skin are reported as painless. The first specific aim of the proposed work addresses quantifying the microneedle-skin interaction as a function of microneedle geometry. The effects of six geometrical features will be considered through in vitro and human studies to measure the (1) force for microneedle insertion, (2) pain caused by microneedles, (3) skin irritation caused by microneedles and (4) resealing after microneedles are removed. Studies emphasize quantitative measurements and mechanism-oriented analysis. The second specific aim addresses quantifying and modeling transdermal transport as a function of transport mechanisms and microneedle geometry. Transport by diffusion, convection and electrophoresis will be studied in vitro, with in vivo validation using delivery of insulin to hairless rats as a model system. Rates and distribution of transdermal transport will be quantified experimentally using transport, microscopic and electrical measurements and will be analyzed using a theoretical model developed from first principles and involving no fitted parameters. Microneedles for transdermal drug delivery could significantly impact medicine by providing (1) painless injections and (2) a user-friendly method for controlled delivery of compounds such as conventional drugs and macromolecules (e.g., proteins, DNA) over hours to days.
| Gupta, Jyoti; Denson, Donald D; Felner, Eric I et al. (2012) Rapid local anesthesia in humans using minimally invasive microneedles. Clin J Pain 28:129-35 |
| Baek, Changyoon; Han, MeeRee; Min, Junhong et al. (2011) Local transdermal delivery of phenylephrine to the anal sphincter muscle using microneedles. J Control Release 154:138-47 |
| Jiang, Jason; Moore, Jason S; Edelhauser, Henry F et al. (2009) Intrascleral drug delivery to the eye using hollow microneedles. Pharm Res 26:395-403 |
| Gill, Harvinder S; Prausnitz, Mark R (2008) Pocketed Microneedles for Drug Delivery to the Skin. J Phys Chem Solids 69:1537-1541 |
| Gill, Harvinder S; Denson, Donald D; Burris, Brett A et al. (2008) Effect of microneedle design on pain in human volunteers. Clin J Pain 24:585-94 |
| Kim, Yeu-Chun; Ludovice, Peter J; Prausnitz, Mark R (2008) Optimization of transdermal delivery using magainin pore-forming peptide. J Phys Chem Solids 69:1560-1563 |
| Wermeling, Daniel P; Banks, Stan L; Hudson, David A et al. (2008) Microneedles permit transdermal delivery of a skin-impermeant medication to humans. Proc Natl Acad Sci U S A 105:2058-63 |
| Kim, Yeu-Chun; Late, Sameer; Banga, Ajay K et al. (2008) Biochemical enhancement of transdermal delivery with magainin peptide: Modification of electrostatic interactions by changing pH. Int J Pharm 362:20-8 |
| Lee, Jeong W; Park, Jung-Hwan; Prausnitz, Mark R (2008) Dissolving microneedles for transdermal drug delivery. Biomaterials 29:2113-24 |
| Kim, Yeu-Chun; Ludovice, Peter J; Prausnitz, Mark R (2007) Transdermal delivery enhanced by magainin pore-forming peptide. J Control Release 122:375-83 |
Showing the most recent 10 out of 11 publications
