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The skin being the largest organ of the body presents a potential route for administration of drugs. Passive transdermal products such as gels, creams and patches deliver drugs effectively across the skin. However, this approach is limited to lipophilic molecules with low molecular weights. Passive transdermal delivery of proteins and peptides which are hydrophilic with high molecular weights is negligible. This led to the development of various ways of surmounting the skin barrier so as to make this route feasible for peptide and protein delivery. The current article reviews various active transdermal technologies with special emphasis on microneedle mediated delivery. Microneedles, especially dissolvable microneedles present an excellent platform for protein and peptide delivery. Significant advances have been made in the past decade in this area. Published literature shows a broad spectrum of molecules being delivered successfully via microneedles. However, success in clinic will give a boost to all the efforts and advances made in this field so far.

The availability of several enhancement techniques has made it possible to study delivery of macromolecules through skin. This study was conducted to evaluate the transdermal delivery of a ~13 kDa protein using iontophoresis, sonophoresis, and microneedles alone or in combination. In vivo delivery experiments were carried out using hairless rats with daniplestim (DP) as the model protein (molecular weight: 12.760 kDa; isoelectric point, 6.2). Delivery enhancement abilities of the above techniques were evaluated at two different drug concentrations in the patch: 2 mg/mL and 5 mg/mL. At a drug loading concentration of 2 mg/mL maximum delivery was seen with the combination of microneedles and iontophoresis. At 5 mg/mL, sonophoresis alone gave a C(max) of 8.22 +/- 5.9 ng/mL and a combination of sonophoresis and iontophoresis gave a C(max) of 4.9 +/- 1.8 ng/mL. The results of this study suggest that combination of microneedles and iontophoresis was the most effective approach in delivering a 13 kDa protein through the skin.

No abstract

Subcutaneous levels of daniplestim were measured following iontophoresis after improving recovery and minimizing fluid loss from the microdialysis probe.