Purpose. The broad aim of this project was to evaluate microneedle technology and iontophoresis for intradermal and transdermal delivery of drugs.

Methods. Microneedle technology was characterized by investigating the formation and closure of microchannels created by soluble and metal microneedles, in vivo, by various techniques including histological sectioning, confocal microscopy, calcein imaging, transepidermal water loss measurements, methylene blue staining and flux studies.

Iontophoresis mediated intradermal delivery of imiquimod was investigated both, in vitro and in vivo. Formulation and iontophoretic parameters were optimized in vitro. In vivo studies were performed in hairless rats to assess the formation and desorption of imiquimod skin depot in skin. Effects of microporation and combination treatment of microneedles and iontophoresis on imiquimod delivery were also studied.

Results. Maltose and metal microneedles effectively created microchannels in hairless rat skin, in a reproducible manner. When exposed to the environment, microchannels closed within 15 hrs for soluble microneedles and pore closure could be delayed for up to 72 hrs by exposing the microporated site to occlusive conditions. Microneedle length had an effect on pore closure times as observed for metal microneedles. Pores closed within 18 hrs for 770 μm long microneedles as compared to 12 hrs for 330 μm long microneedles.

Iontophoresis treatment increased permeation levels of imiquimod into skin. Increasing the drug load in the donor formulation resulted in a direct increase in drug delivery. Iontophoresis, microporation and combination treatment, all resulted in comparable levels and enhanced imiquimod delivery into skin as compared to passive conditions. Imiquimod formed a depot in the skin for all treatment conditions which depleted over a period of several days, thereby allowing prolonged delivery.

Conclusion. Microneedle technology is a very appealing enhancement method for drug delivery due to the reversible nature of pore formation in skin. Pore closure can be controlled by introducing occlusive conditions in the transdermal system.

Iontophoresis enhanced imiquimod delivery into skin. Imiquimod formed a depot in the stratum corneum layer of skin which depleted over a period of 72 hrs. Iontophoresis, microneedles and combination treatment of microneedles and iontophoresis resulted in comparable levels indicating the feasibility of developing enhancement mediated transdermal systems for controlled delivery of imiquimod into skin.