Hollow microneedles for molecular transport across skin

As a novel drug delivery technology, we have developed arrays of microscopic needles, which are capable of providing pathways for molecular transport across the skin without the pain associated with conventional injections. Pathways through the stratum comeum and viable epidermis created by hollow microneedles allow transport of molecules otherwise unable to cross the skin.; A fabrication scheme to create hollow tapered microneedles based on laser micromachining and the LIGA process has been created. Both metals and polymers were investigated a s mold materials. The high quality, reproducible control over geometry, and ease of removal of polyethylene terephthalate molds make them the preferred choice.; The insertion force of microneedles in the skin of human subjects was measured as a function of microneedle geometry. The relationship between the full interfacial area of the microneedle and the insertion force was found be linear. This behavior agrees with a fracture mechanics-based model balancing the energy delivered to the skin and the energy necessary to puncture the skin. The puncture toughness of the skin was determined to be 30.1 +/- 0.6 kJ/m2.; The fracture force of microneedles was measured as a function of microneedle geometry. Fracture force was found to increase with wall thickness, wall angle, and possibly tip diameter. This behavior agrees with analytical and finite element simulation models of fracture force. Both models predict the trends of the data with respect to geometry, but the analytical model was found to have better quantitative agreement with the data.; Microneedles were used to deliver insulin to diabetic rats. Both pharmacokinetic and pharmacodynamic responses were measured. The blood glucose level of diabetic rats was reduced to 47% of its original value during four hours of insulin delivery through hollow microneedles. The concentration of insulin in the rat's blood plasma was found to be 5.5 +/- 3 muU/ml after 30 minutes of insulin delivery and 12 +/- 4 muU/ml after 4 hours of delivery. The delivery of insulin through microneedles into the blood was then predicted by a simple Fickian diffusion model.