Delivery of large molecular protein using flat and short microneedles prepared using focused ion beam (FIB) as a skin ablation tool.

Many studies have been reported in the literature on the effects of various geometries and lengths of microneedles (MNs) on transdermal drug delivery using a variety of drug molecules. In particular, sharp-tipped MNs have been used to disrupt the top layer of the skin, namely, stratum corneum (SC). It has also been shown that short- and flat-tipped MNs can pierce the SC and they have the potential to increase drug permeability. However, there is little work that explores MNs as a skin ablative tool with a view to increasing skin permeability. To address this point, well-defined small patterns (size of individual pattern 10-20 μm) on the tip of flat MN (tip radius of individual MN ∼250 μm) were created and their effects evaluated on the permeability of bovine serum albumin (BSA), which is chosen as a model drug of high molecular weight. The patterns on the tip of flat MN act as rough surfaces (e.g. like sand paper) which when applied on the surface of the skin ablate the SC layer. Focused ion beam (FIB) has been used as the fabrication technique for the MNs. The permeability data are then compared with the other data for flat- and sharp-tipped MN. The permeability data from passive diffusion experiments are used as the reference case. The exact number of MNs or patterns in the flat and patterned MN patches is not considered as important as they have not been designed to pierce the skin. However, this is an important consideration in the case of sharp MNs as they pierce and create cavities in the skin. It is found that the delivery of BSA with the fabricated flat and patterned MNs gave similar but somewhat lower drug permeation profile in comparison to the sharp MNs. Passive diffusion showed no permeation, as would be expected due to the large size of the chosen molecule.