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The authors of the study believe it could have significant implications for the discovery of new dermatological products for major diseases such as psoriasis.
New research, published in the Journal of Investigative Dermatology by scientists from the United Kingdom and United States, challenges current theories on the permeation and penetration of large molecular weight molecules across and into the skin. It was traditionally believed that drugs with a molecular weight of more than 500 Daltons will not permeate the skin, and therefore, could not be applied topically to treat skin diseases. According to the authors of this new study, it is possible for biologic drugs to achieve topical efficacy. The research, which was carried out by the University of Reading, UK in collaboration with GlaxoSmithKline (GSK) and topical formulation specialists, MedPharm, could have significant implications on the discovery of new dermatological products for major diseases such as psoriasis.
In the study, researchers evaluated the potential of an aptamer as an active target for the treatment of a range of skin diseases such as psoriasis and atopic dermatitis. The aptamer was a RNA-based 62-unit nucleotide with a molecular weight of 20,395 Daltons. The group has shown using ex-vivo human skin that the aptamer not only passed through the stratum corneum but also could be detected at therapeutic levels in the epidermal and dermal layers. The research further 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.
Large biological molecules such as peptides and nucleotides are being increasingly identified as important drug targets. This research opens up the possibility that macromolecules could be applied to the skin and treat dermatological diseases that have no current satisfactory treatment.
“These findings are potentially very significant for the development of new dermatological products,” Jon Lenn, MedPharm’s vice president in charge of US Operations and lead author of the paper, commented in a press statement. “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.”
Professor 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 behavior of different drug classes, the better we can help clients de-risk their development programs whilst providing optimised and bespoke formulations.”
MedPharm, a contract provider of topical and transdermal product design and formulation development services, conducts its own performance testing using ex-vivo human skin and specific disease activity models at its North Carolina laboratories. Its scientists are validating models to enable clients to demonstrate bioequivalence of generic drugs without the need for clinical trials. They are also working on demonstrating the permeation and activity of formulations containing new chemical entities to de-risk future clinical trials.
Source: MedPharm