Breakthrough in Topical Delivery of Large Molecule Drugs

New research by UK and US scientists published online in the Journal of Investigative Dermatology challenges current theories on the permeation and penetration of large molecular weight molecules across and into human skin. The authors of the study believe it could have significant implications for the discovery of new dermatological products for major diseases such as psoriasis. It suggests that ‘biologic’ type drugs could achieve topical efficacy. The work was performed by the University of Reading, UK in collaboration with GlaxoSmithKline (GSK) and leading topical formulation specialists, MedPharm.

Traditional thinking has previously suggested that drugs with a molecular weight of above 500 Daltons will not permeate across the skin and hence cannot be applied topically for the treatment of dermatological diseases. The aptamer used in this recent research was a RNA-based 62 unit nucleotide with a molecular weight of 20,395 Daltons. The aptamer is an active target for the treatment of a range of skin diseases such as psoriasis and atopic dermatitis.

The group has shown using ex vivo human skin that the aptamer not only passed through the stratum corneum but also can be detected at therapeutic levels in the epidermal and dermal layers. Furthermore, the research showed that the aptamer remained in its biologically active conformation and was capable of binding to endogenous IL-23, a key biomarker for important inflammation pathways.

With the explosion in knowledge of molecular biological mechanisms, larger biological molecules such as peptides and nucleotides are being increasingly identified as important drug targets. This research opens up the possibility that similar ‘biologics’ could be applied to the skin and treat dermatological diseases with no current satisfactory treatment.

Dr Jon Lenn, MedPharm’s Vice President of US Operations, who is lead author of the paper, commented, “These findings are potentially very significant for the development of new dermatological products. The data suggest we can expand the boundaries of molecules suitable for topical treatments and opens the possibility to treat difficult diseases such as psoriasis and atopic dermatitis with drugs previously thought to be impossible to deliver topically into the skin.”

Prof. Brown, MedPharm’s Chief Scientific Officer and one of the co-leaders of the study added, “This work exemplified how MedPharm is continuing to support research which expands our understanding of drug delivery across and into the skin. The more we understand about the barrier properties of skin and the behaviour of different drug classes the better we can help clients de-risk their development programmes whilst providing optimised and bespoke formulations.”

MedPharm conducts its own performance testing using ex-vivo human skin and specific disease activity models at its rapidly expanding North Carolina laboratories. MedPharm scientists are validating models to enable clients to demonstrate bioequivalence of generics without the need for clinical trials and demonstrating the permeation and activity of formulations containing new chemical entities to de-risk future clinical trials.

Read the full research article on Journal of Investigative Dermatology here