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G. Mahadevan, P. Selvaganapathy, H. Sheardown; Hybrid Flexible Microneedle Arrays for Enhanced Scleral Permeability. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5160.
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© ARVO (1962-2015); The Authors (2016-present)
Conventionally microfabricated hollow microneedle arrays for drug delivery require expensive clean room facilities that yield rigid microstructures that preclude ease of assembly into flexible substrates required for ocular drug delivery. We have developed a new hybrid technique that allows for simple integration of two dimensional rigid microneedle arrays into a flexible elastomeric platform suitable for intrascleral release of drugs to the posterior pole. In this work, a 3x3 array of hollow glass microneedle arrays was constructed and integrated into a device. We investigated whether the device could penetrate excised bovine sclera by performing in vitro permeability experiments with 40 kDa FITC-Dextran to determine increased flux in bovine sclera using the microneedle array.
Microneedle structures were obtained by wet etching of 165 µm OD/10 µm ID fused silica capillary tubings and assembled into a 3X3 array using photolithographically defined PDMS substrates. Resultant microneedles had tip diameters equivalent to the native IDs of the supplied tubing and had taper lengths of 500 µm. For release studies, the array was coupled to a reservoir and placed on a 10-mm diameter section of sclera isolated from the superior temporal quadrant with pressure actuation to release the drug over 8 hours. Using a standard two chamber diffusion cell apparatus, total flux was plotted for control sclera and device treated sclera. The apparent permeability coefficient for the device treated sclera was calculated.
Hollow glass microneedle arrays successfully penetrated scleral tissues without fracture or damage to the microneedles upon insertion, penetration and removal. Moreover due to frictional forces, the array remained embedded within the scleral matrix until manually removed. Release of drug into the scleral tissue was performed without any clogging or obstruction of the microneedle lumen. The device increased permeability of the scleral tissue over control scleral sections.
This is the first reported method of a drug delivery device using microneedles that combines the accuracy of photolithographic patterning for flexible mold construction with inexpensive microneedle fabrication techniques using standard wet lab chemical processes.
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