Microinfusion using hollow microneedles.
PURPOSE: 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. METHODS: Glass microneedles were inserted to a depth of 720-1080 microm 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. RESULTS: Single microneedles inserted into skin without retraction were able to infuse sulforhodamine solution into the skin at flow rates of 15-96 microl/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 microl/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. CONCLUSIONS: 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.