Proteins and peptides: Strategies for delivery to and across the skin

Despite the increased availability of therapeutic proteins and peptides, delivery remains almost entirely via hypodermic needle. Transdermal delivery offers an attractive noninvasive route of administration but is limited by the skin's barrier to penetration. Extensive research has been directed at developing effective methods to enhance delivery of peptides and proteins to and across the skin. Strategies include formulation optimisation, conjugation to increase peptide lipophilicity and incorporation of chemical or biological modifiers to transiently reduce stratum corneum barrier function. A number of physical technologies, including iontophoresis, electroporation and sonophoresis, have been developed that apply different forms of energy to disrupt the barrier. In addition, minimally invasive techniques, such as microneedles and jet propulsion, bypass the stratum corneum barrier to permit direct access to the viable epidermis. This article reviews the current state of the art in the delivery of proteins and peptides to and across the skin. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3591-3610, 2008.