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CriticalSorb™: enabling systemic delivery of macromolecules via the nasal route

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Abstract

Systemic delivery of proteins via the nasal route has to date been limited by their poor absorption across the nasal mucosa, and the less than optimal tolerability of known permeation enhancers. We have recently developed a highly effective nasal delivery system (CriticalSorb™) based on Solutol HS15. Extensive toxicology studies have shown CriticalSorb™ to be very well tolerated, non-toxic and non-irritant. Cell culture and ex vivo-isolated tissue studies have shown it to promote transport of molecules mainly via transcellular but also to some extent, via paracellular routes. Pharmacokinetic/pharmacodynamic studies in rats, rabbits, non-human primates and recently in man have demonstrated significantly enhanced systemic delivery of nasally administered proteins including insulin (~6 kDa) and human growth hormone (~22 kDa), and pharmacodynamics similar to those after subcutaneous injection. CriticalSorb™ therefore opens up the possibility of developing nasal spray formulations for macromolecules such as proteins.

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Acknowledgments

The authors would like to thank BioKnex and the Wellcome Trust for funding, Dr. Snow Stolnik, Dr. Emilia Moradi, Dr. Driton Vllasaliu and Saif Shubber at the University of Nottingham for physicochemical characterisation and cell culture studies, and Professor David Brayden and Dr. Victoria Bzik for mechanism of action studies.

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Correspondence to Andrew L. Lewis.

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Lewis, A.L., Jordan, F. & Illum, L. CriticalSorb™: enabling systemic delivery of macromolecules via the nasal route. Drug Deliv. and Transl. Res. 3, 26–32 (2013). https://doi.org/10.1007/s13346-012-0089-8

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