Overcoming the barrier: Peptide mediated topical delivery of nucleic acids in skin

posted Mar 22, 2016, 1:35 AM by SRamachandran igib   [ updated Mar 22, 2016, 1:57 AM ]

Skin is the largest organ of the human body. Its large surface area and easy accessibility as well as the advantage of easy monitoring of the after-effects of treatment makes it an attractive choice for delivery of different kinds of molecules for both pharmaceutical (i.e. as a drug) and cosmeceutical (i.e. for skin beautification) purpose. Two modes of delivery are predominant: topical (to skin) or transdermal (through skin) - depending upon the final destination of these molecules.  Topical delivery is required when one attempts to treat skin diseases e.g. psoriasis, atopic dermatitis, vitiligo or melanoma or for treatment of conditions like wounds or sunburns or even for application of cosmetics. Transdermal delivery is required when one needs to send drugs through the skin into the dermis in order to go into circulation and reach some other affected organ. However drug delivery to and through the skin poses its own challenges. Skin allows favorable entry of small molecules which are less than 500Da in size and lipophilic in nature that can passively diffuse whereas all others usually need active carriers or physical interventions for transport. The complex skin architecture makes it very difficult for large biomolecules to pass to or through the skin. In most cases, harsh physical or chemical techniques are used for drug delivery to skin leading to toxic effects. We have developed an amphipathic peptide that can not only penetrate the uncompromised skin and efficiently enter skin cells but can also deliver plasmid DNA efficiently by forming nanometric complexes without any additional physical or chemical intervention. We observe efficient gene expression up to the highly proliferating basal layer of the skin without observing any adverse reactions or toxic effects after delivery of reporter plasmids. Our data indicates that entry mechanism possibly involves reversible modulation of junction proteins in the skin  along with transient changes in skin structure. This peptide is likely to also find use as an efficient transporter of therapeutic nucleic acids and possibly other drugs to skin.

Manika Vij, Poornemaa Natarajan, Bijay Ranjan Pattnaik, Shamshad Alam, Nidhi Gupta, Deenan Santhiya, Rajpal Sharma, Archana Singh, Kausar Mahmood Ansari, Rajesh S. Gokhale, Vivek T. Natarajan, Munia Ganguli.

Non-invasive topical delivery of plasmid DNA to the skin using a peptide carrier.

J Control Release; January; 2016 

doi: 10.1016/j.jconrel.2015.12.017. Epub 2015 Dec 14.