A compact and disposable transdermal drug delivery system

Available online at www.sciencedirect.com

Microelectronic Engineering 85 (2008) 1066–1073 www.elsevier.com/locate/mee

A compact and disposable transdermal drug delivery system M. Matteucci a,*, M. Casella b,e, M. Bedoni b,c, E. Donetti c, M. Fanetti d, F. De Angelis e, F. Gramatica b, E. Di Fabrizio e,f b

a Sincrotrone Trieste, I-34012 Basovizza-Trieste, Italy Biophysics and Nanomedicine Laboratory, Polo Tecnologico, Fondazione Don Gnocchi IRCCS-ONLUS, Via Capecelatro 66, 20148 Milan, Italy c Universita` degli Studi di Milano, Via Mangiagalli 31, 20133 Milan, Italy d CNR-INFM and Dipartimento di Matematica e Fisica, Universita` Cattolica, via dei Musei 41, 25121 Brescia, Italy e BIONEM Laboratory, Dipartimento di Medicina Sperimentale e Clinica, Universita` Magna Graecia, viale Europa, 88100 Catanzaro, Italy f INFM-TASC- S.S.14 km 163,5 in Area Science Park, 34012 Basovizza-Trieste, Italy

Received 8 October 2007; received in revised form 13 December 2007; accepted 27 December 2007 Available online 12 January 2008

Abstract This work presents a portable transdermal drug delivery system that combines a magnetically actuated micro gear pump with a microneedle array. Micropart fabrication is performed through DXRL and LIGA techniques. The manufacturing process of both micropump and microneedle array are described together with wear issues. Results show that the assembled device can deliver rates that go from 0.1 to 1.2 ml/min at gear speed ranging from 1000 to 8500 rpm. First skin piercing experiments are also described. Ó 2008 Elsevier B.V. All rights reserved. Keywords: Transdermal drug delivery; LIGA; Deep X-ray lithography; Soft lithography

1. Introduction Amongst all techniques used for releasing drugs in a controlled way into the human body, transdermal drug delivery (TDD) is now widely recognized as one of the most promising ones, with a large number of commercialized applications [1]. Its great potential is due to the possibility of significantly improving the treatment of certain diseases as well as the patient’s comfort. The most common transdermal systems present on the market are based on semi-permeable membranes (the so-called ‘‘patches”): several drugs from nicotine to nitroglycerin (angina therapeutic agent) are delivered by means of this method. The spreading of transdermal patches is widening; nevertheless, it is limited by the possibility of delivering, by passive diffusion, only the drugs that have small molecular weight (