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Review
. 2021 Nov;46(6):743-758.
doi: 10.1007/s13318-021-00716-x. Epub 2021 Sep 6.

Advances in Thiopurine Drug Delivery: The Current State-of-the-Art

Ahmed B Bayoumy  1 , Femke Crouwel  2 , Nripen Chanda  3 , Timothy H J Florin  4 , Hans J C Buiter  5 , Chris J J Mulder  2 , Nanne K H de Boer  2
Affiliations
Review

Advances in Thiopurine Drug Delivery: The Current State-of-the-Art

Ahmed B Bayoumy et al. Eur J Drug Metab Pharmacokinet. 2021 Nov.

Abstract

Thiopurines (mercaptopurine, azathioprine and thioguanine) are well-established maintenance treatments for a wide range of diseases such as leukemia, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and other inflammatory and autoimmune diseases in general. Worldwide, millions of patients are treated with thiopurines. The use of thiopurines has been limited because of off-target effects such as myelotoxicity and hepatotoxicity. Therefore, seeking methods to enhance target-based thiopurine-based treatment is relevant, combined with pharmacogenetic testing. Controlled-release formulations for thiopurines have been clinically tested and have shown promising outcomes in inflammatory bowel disease. Latest developments in nano-formulations for thiopurines have shown encouraging pre-clinical results, but further research and development are needed. This review provides an overview of novel drug delivery strategies for thiopurines, reviewing modified release formulations and with a focus on nano-based formulations.

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Conflict of interest statement

AB Bayoumy, F Crouwel, N Chanda and HJC Buiter have nothing to disclose. THJ Florin is a director of an Australian startup company ProdrugXtend Pty Ltd, which owns a PCT relating to thiopurines. CJJ Mulder has served as a consultant and principal investigator for HLW Pharma BV, Douglas Pharma and Arega. NKH de Boer has served as a speaker for AbbVie and MSD and has served as consultant and principal investigator for TEVA Pharma BV and Takeda. He has received a (unrestricted) research grant from Dr. Falk, TEVA Pharma BV, MLDS and Takeda, all outside the submitted work.

Figures

Fig. 1
Fig. 1
Chemical properties of the different thiopurines. The thiopurines are divided into two classes (imidazole and non-imidazole thiopurines) and two groups (mercaptopurine and thioguanine groups). Highlighted in blue is the imidazole group. IBD inflammatory bowel disease, SLE systemic lupus erythematosus, RA rheumatoid arthritis, PAN polyarthritis nodosa, ITP immune-mediated thrombocytopenia, AIH autoimmune hepatitis
Fig. 2
Fig. 2
Simplified overview of various delivery platforms that have been used for thiopurine drug delivery, created with BioRender.com
See this image and copyright information in PMC

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