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.

Arrays of micrometer-scale needles could be used to deliver drugs, proteins, and particles across skin in a minimally invasive manner. We therefore developed microfabrication techniques for silicon, metal, and biodegradable polymer microneedle arrays having solid and hollow bores with tapered and beveled tips and feature sizes from 1 to 1,000 μm. When solid microneedles were used, skin permeability was increased in vitro by orders of magnitude for macromolecules and particles up to 50 nm in radius. Intracellular delivery of molecules into viable cells was also achieved with high efficiency. Hollow microneedles permitted flow of microliter quantities into skin in vivo, including microinjection of insulin to reduce blood glucose levels in diabetic rats.

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Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies

Precise microinjection into skin using hollow microneedles.

Background: Compliance with glucose monitoring by patients with diabetes is poor because of the pain and inconvenience of conventional blood collection using lancets. To improve compliance, and thereby reduce morbidity and mortality associated with poor glucose control, this study sought to develop and test minimally invasive microneedles to extract dermal interstitial fluid (ISF) for glucose monitoring. Methods: We used a thermal puller to fabricate individual or multi-needle arrays of glass microneedles with tip radii of 15–40 µm to penetrate 700–1,500 µm deep into the skin of anesthetized hairless rats or conscious, normal, adult, human subjects. After applying a vacuum of 200–500 mm Hg for 2–10 min, we extracted ISF and measured glucose concentration. These measurements were compared with glucose levels in blood collected from the tail vein of rats or finger stick on humans. Results: Using this procedure, 1–10 µL of ISF was extracted out of holes punctured in the skin using microneedles. Human subject...

Minimally invasive extraction of dermal interstitial fluid for glucose monitoring using microneedles.

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

Background: Interstitial fluid (ISF) is a specimen of increasing interest for glucose measurements because it can be obtained in a minimally invasive manner. Our previous study showed that sufficient ISF can be obtained using microneedles to measure glucose with a conventional electrochemical glucose monitor. The aim of this study was to assess the trueness of this glucose monitor using split-sample comparison with whole blood. We used ISF as specimen and our gas chromatography/mass spectrometry (GC/MS) method as reference. Methods: We obtained 50 ISF samples and 40 whole blood samples from hairless Sprague- Dawley rats and analyzed for glucose by both methods. Results: For whole blood, a non-significant bias of 5.7% (±2 SD: −54.9% to 66.3%) was determined. ISF glucose measurements showed a significant constant bias of 29.5% (±2 SD: −85.0% to 144%), which seems to be caused in part by the lack of red blood cells in ISF. The correlation coefficients were 0.782 and 0.679 for whole blood and ISF, respectivel...

/pdf/assessment-of-trueness-of-a-glucose-monitor-using-1zx74ckpm6.pdf

Ping M. Wang

Papers

Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies

Precise microinjection into skin using hollow microneedles.

Minimally invasive extraction of dermal interstitial fluid for glucose monitoring using microneedles.

Microinfusion Using Hollow Microneedles

Assessment of Trueness of a Glucose Monitor Using Interstitial Fluid and Whole Blood as Specimen Matrix