Microneedles for drug and vaccine delivery.

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.

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Microinfusion Using Hollow Microneedles

With the limitations of oral drug delivery and the pain and needle phobias associated with traditional injections, drug delivery research has focused on the transdermal delivery route A formidable barrier to transdermal drug delivery is the stratum corneum, the superficial layer of the skin In the last 10 years, microneedles were proposed as a mechanical tool to pierce through the stratum corneum, in order to create drug delivery channels without stimulating underlying pain nerves Since then, the field of microneedles has rapidly evolved to spawn a plethora of potential transdermal applications In this review, the authors provide an overview of the progress in microneedle research and design, and the advancements that have been made in employing this technology for transdermal applications

Microneedles and transdermal applications

https://iopscience.iop.org/article/10.1088/2058-8585/aace28/pdf

Principles of aerosol jet printing

http://drugdelivery.chbe.gatech.edu/Papers/2011/Gupta%20Biomaterials%202011.pdf

Infusion pressure and pain during microneedle injection into skin of human subjects

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

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Elizabeth A. Costner

Papers

Fluid dynamics in conically tapered microneedles