Microinjection into skin using microneedles
Although transdermal drug delivery provides patient convenience and sustained delivery in contrast to painful hypodermic injections, skin's low permeability prevents passive delivery of most drugs. The development of microneedles that penetrate the skin barrier, but are small enough not to stimulate nerves, has the potential to deliver drugs across skin in a painless way. In previous studies, solid silicon microneedles have been shown to increase skin permeability for transdermal diffusion of a wide range of molecules. However, controlled injection by convective flow into skin using hollow microneedles has remained a challenge. To address this challenge, the goals of this study were (i) to provide experimental measurements coupled with numerical simulations to quantitatively describe fluid mechanics of flow within microneedles over a range of experimental conditions and needle geometries, (ii) to demonstrate and study the effects of diffusion-based delivery of insulin to diabetic rats in vivo using solid and hollow microneedles and (iii) to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow.
Experimentally, we quantified the relationship between pressure drop and flow rate through microneedles as a function of fluid viscosity and microneedle length, diameter, and cone half-angle. Microneedle tip diameter and taper angle were the primary controlling parameters for flow through conically tapered microneedles as shown by numerical simulations. Flow rates over a range of 1.4--56 μl/s were achieved through microneedles (in the absence of skin) with pressure drops in the range of 4.6--196.5 kPa.
This work also studied the use of solid microneedle arrays to insert into the skin of diabetic animals for transdermal delivery of insulin. Blood glucose levels dropped by as much as 80% in diabetic hairless rats in vivo. Larger drops in blood glucose level and larger plasma insulin concentrations were shown due to higher donor solution insulin concentration, shorter microneedles insertion time and fewer repeated insertions.
The final scope of this work was to determine the effect of microneedle geometry and infusion protocols on microinfusion flow rate into skin in vitro. Infusion flow rates ranged from 21 to 1130 μl/h was demonstrated using these microneedles. The presence of a bevel at the microneedle tip, larger retraction distance and insertion depth, larger infusion pressure and the presence of hyaluronidase led to larger infusion flow rates.
0541: Biomedical research