Physical Enhancement of Transdermal Drug Application: Is Delivery Technology Keeping up with Pharmaceutical Development?

Abstract

Advances in molecular biology have given us a wide range of protein and peptide-based drugs that are unsuitable for oral delivery because of their high degree of first-pass metabolism. Though parenteral delivery is the obvious answer, for the successful development of commercial chronic and self-administration usage formulations it is not the ideal choice. Transdermal delivery is emerging as the biggest application target for these agents, however, the skin is extremely efficient at keeping out such large molecular weight compounds and therapeutic levels are never going to be realistically achieved by passive absorption. Physical enhancement mechanisms including: iontophoresis, electroporation, ultrasound, photomechanical waves, microneedles and jet-propelled particles are emerging as solutions to this topical delivery dilemma. Adding proteins and peptides to the list of other large molecular weight drugs with insufficient passive transdermal fluxes to be therapeutically useful, we have a collection of pharmacological agents waiting for efficient delivery methods to be introduced. This article reviews the current state of physical transdermal delivery technology, assesses the pros and cons of each technique and summarises the evidence-base of their drug delivery capabilities.

The effect of heat on skin permeability

“…The present study suggests that the mechanism may involve decomposition and vaporization of the stratum corneum, which removes tissue to generate micron-scale holes. This contrasts with the mechanisms of chemical, electrical (iontophoresis and electroporation), and ultrasonic enhancement of transdermal transport, which each involve structural rearrangements of stratum corneum on the molecular or nanometer scale (Cross and Roberts, 2004). It also differs from microneedles, which similarly make micron-scale holes in the skin, but do so by cutting a pathway without removing tissue (Prausnitz, 2004).…”

“…Drugs that cross the stratum corneum barrier can generally diffuse to deeper capillaries for systemic distribution. For this reason, most approaches to increase transdermal delivery have emphasized disruption of stratum corneum microstructure using chemical or physical methods (Cross and Roberts, 2004;Down and Harvey, 2003;Schuetz et al, 2005).…”

Fractional CO2 laser‐assisted drug delivery

“…(e.g., drug-vehicle optimization, prodrugs, liposomes, hydration, and chemical enhancers) as well as physical modulation techniques such as iontophoresis, electroporation, ultrasound, photomechanical waves, microneedles, and superficial laser ablation [15][16][17]. Erbium lasers in particular have been used for laser-assisted cutaneous drug delivery [18][19][20][21], but the potential for deep AFR-assisted drug delivery has not been studied.…”

Penetration Enhancement Techniques

“…Suggestions have been made that many clinically important proteins such as insulin (6000 Da) and hematoprotien (48000 Da) are within or close to the delivery capability range of PW's. However; this relatively new technique does not yet seem to have produced any human clinical data [27,28].…”