http://drugdelivery.chbe.gatech.edu/Papers/2004/Prausnitz%20ADDR%202004.pdf

Microneedles for transdermal drug delivery.

The past twenty five years have seen an explosion in the creation and discovery of new medicinal agents. Related innovations in drug delivery systems have not only enabled the successful implementation of many of these novel pharmaceuticals, but have also permitted the development of new medical treatments with existing drugs. The creation of transdermal delivery systems has been one of the most important of these innovations, offering a number of advantages over the oral route. In this article, we discuss the already significant impact this field has made on the administration of various pharmaceuticals; explore limitations of the current technology; and discuss methods under exploration for overcoming these limitations and the challenges ahead.

Current status and future potential of transdermal drug delivery

Microneedles for drug and vaccine delivery.

Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery

Dissolving microneedles for transdermal drug delivery.

Purpose. The purpose of this study was to design and fabricate arrays of solid microneedles and insert them into the skin of diabetic hairless rats for transdermal delivery of insulin to lower blood glucose level. 
Methods. Arrays containing 105 microneedles were laser-cut from stainless steel metal sheets and inserted into the skin of anesthetized hairless rats with streptozotocin-induced diabetes. During and after microneedle treatment, an insulin solution (100 or 500 U/ml) was placed in contact with the skin for 4 h. Microneedles were removed 10 s, 10 min, or 4 h after initiating transdermal insulin delivery. Blood glucose levels were measured electrochemically every 30 min. Plasma insulin concentration was determined by radioimmunoassay at the end of most experiments. 
Results. Arrays of microneedles were fabricated and demonstrated to insert fully into hairless rat skin in vivo. Microneedles increased skin permeability to insulin, which rapidly and steadily reduced blood glucose levels to an extent similar to 0.05-0.5 U insulin injected subcutaneously. Plasma insulin concentrations were directly measured to be 0.5-7.4 ng/ml. Higher donor solution insulin concentration, shorter insertion time, and fewer repeated insertions resulted in larger drops in blood glucose level and larger plasma insulin concentrations. 
Conclusions. Solid metal microneedles are capable of increasing transdermal insulin delivery and lowering blood glucose levels by as much as 80% in diabetic hairless rats in vivo.

/pdf/transdermal-delivery-of-insulin-using-microneedles-in-vivo-32wbrdvk2r.pdf

Transdermal Delivery of Insulin Using Microneedles in Vivo

The goal of this study was to design, fabricate, and test arrays of hollow microneedles for minimally invasive and continuous delivery of insulin in vivo. As a simple, robust fabrication method suitable for inexpensive mass production, we developed a modified-LIGA process to micromachine molds out of polyethylene terephthalate using an ultraviolet laser, coated those molds with nickel by electrodeposition onto a sputter-deposited seed layer, and released the resulting metal microneedle arrays by selectively etching the polymer mold. Mechanical testing showed that these microneedles were sufficiently strong to pierce living skin without breaking. Arrays containing 16 microneedles measuring 500 /spl mu/m in length with a 75 /spl mu/m tip diameter were then inserted into the skin of anesthetized, diabetic, hairless rats. Insulin delivery through microneedles caused blood glucose levels to drop steadily to 47% of pretreatment values over a 4-h insulin delivery period and were then approximately constant over a 4-h postdelivery monitoring period. Direct measurement of plasma insulin levels showed a peak value of 0.43 ng/ml. Together, these data suggest that microneedles can be fabricated and used for in vivo insulin delivery.

Hollow metal microneedles for insulin delivery to diabetic rats

The aim of the study is 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. Glass microneedles were inserted to a depth of 720–1080 μm into human cadaver skin to microinfuse sulforhodamine solution at constant pressure. Flow rate was determined as a function of experimental parameters, such as microneedle insertion and retraction distance, infusion pressure, microneedle tip geometry, presence of hyaluronidase, and time. Single microneedles inserted into skin without retraction were able to infuse sulforhodamine solution into the skin at flow rates of 15–96 μl/h. Partial retraction of microneedles increased flow rate up to 11.6-fold. Infusion flow rate was also increased by greater insertion depth, larger infusion pressure, use of a beveled microneedle tip, and the presence of hyaluronidase such that flow rates ranging from 21 to 1130 μl/h were achieved. These effects can be explained by removing or overcoming the large flow resistance imposed by dense dermal tissue, compressed during microneedle insertion, which blocks flow from the needle tip. By partially retracting microneedles after insertion and other methods to overcome flow resistance of dense dermal tissue, protocols can be designed for hollow microneedles to microinfuse fluid at therapeutically relevant rates.

/pdf/microinfusion-using-hollow-microneedles-3lndrckxzd.pdf

Microinfusion Using Hollow Microneedles

http://drugdelivery.chbe.gatech.edu/Papers/2006/Martanto%20J%20Control%20Release%202006.pdf

Mechanism of fluid infusion during microneedle insertion and retraction.

Toward achieving painless injections and other microfluidic applications, we microfabricated conically tapered needles of micron dimensions. The relationship between pressure drop and flow rate through microneedles was experimentally quantified as a function of fluid viscosity and microneedle length, diameter, and cone half-angle. At Reynolds numbers 100, dimensionless pressure drop (2P/v 2 ) sharply decreased with increasing Reynolds number, indicating the importance of viscous forces. At larger Reynolds numbers, the flow was almost inviscid, as indicated by a weak dependency of dimensionless pressure drop on Reynolds number. Numerical simulations showed good agreement with experimental data and predicted that flow through conically tapered microneedles is primarily controlled by the diameter and taper angle at the microneedle tip. A characteristic feature of flow through conically tapered microneedles is a favorable axial pressure gradient that accelerates fluid through the microneedle, thus inhibiting growth of the viscous boundary layer on the microneedle wall. © 2005 American Institute of Chemical Engineers AIChE J, 51: 1599 –1607, 2005

/pdf/fluid-dynamics-in-conically-tapered-microneedles-3pckpmz7kr.pdf

Wijaya Martanto

Papers

Transdermal Delivery of Insulin Using Microneedles in Vivo

Hollow metal microneedles for insulin delivery to diabetic rats

Microinfusion Using Hollow Microneedles

Mechanism of fluid infusion during microneedle insertion and retraction.

Fluid dynamics in conically tapered microneedles