Transcending the Skin Barrier to Deliver Peptides and Proteins Using Active Technologies

Abstract

Peptides and proteins have been investigated as promising therapeutic agents over the past decade. These macromolecules are conventionally administered by the parenteral route because oral delivery is associated with degradation in the gastrointestinal tract. Transdermal delivery presents a promising alternative route of drug delivery, avoiding pain associated with parenteral administration and degradation issues associated with oral delivery. However, the barrier properties of skin limit delivery to only small, moderately lipophilic molecules. Hence, hydrophilic macromolecules like peptides and proteins cannot passively permeate across skin. Active physical enhancement approaches such as iontophoresis electroporation, microneedles treatment, and sonophoresis have been developed to assist transdermal delivery of peptides and proteins. This review describes active physical transdermal enhancement approaches for transdermal delivery of peptides and proteins. The mechanisms associated with each technique and important parameters governing transdermal delivery of peptides and proteins are discussed in detail. Combinations of enhancement techniques for synergistic enhancement in protein and peptide delivery are also discussed.

Transdermal drug delivery: 30 + years of war and still fighting!

“…The number of publications addressing these technologies, especially microneedles, is growing exponentially and recent, authorative reviews are available in the literature [19][20][21][22][23][24]. In each approach, new, aqueous pathways are created across the outer few hundred microns (give or take) of the skin allowing the barrier function of the SC to be 'short-circuited' and relaxing two key limitations of passive transdermal delivery:…”

Epidermal Lipids and the Intercellular Pathway

“…Sonophoresis may both alter the physical state of the intercellular lamellae and create transcellular pathways (Rao and Nanda 2009 ). Electroporation increases the permeability of the stratum corneum by opening or creating aqueous channels, through which relatively large water soluble molecules can pass (Singh et al 2012 ).…”

Microneedles for drug delivery: trends and progress

“…One such example for vaccines delivery is reported by Edmonston-Zagreb for measles vaccination (Nordquist et al, 2007;Herwadkar & Banga, 2012;Kis et al, 2012;Singh et al, 2012;Edens et al, 2013;Koutsonanos et al, 2013;Ling & Chen, 2013;Cai et al, 2014;Gill et al, 2014). Vaccinations have the capacity to be delivered using MN patches, which require the patient to have no specialized training or the need for cold/refrigerated storage; this in turn can reduce the spread of diseases Edens et al, 2013).…”