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bioRxiv · 10.1101/2021.08.15.456403

Polymer microparticles prolong delivery of the 15-PGDH inhibitor SW033291

Dogan, A. B.·Rohner, N. A.·Smith, J. N. P.·Kilgore, J. A.·Williams, N. S.·Markowitz, S. D.·von Recum, H. A.·Desai, A. B.
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Abstract

As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. While bolus parenteral administrations have become standard clinical practice, an extended delivery platform would achieve steady state concentrations over a longer time period with fewer administrations. This study lays the foundation for the development of a sustained release platform for the delivery of (+)SW033291, a potent, small-molecule inhibitor of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme, which has previously demonstrated efficacy in a murine model of pulmonary fibrosis. Herein, we leverage fine-tuned cyclodextrin microparticles - specifically {beta}-CD microparticles ({beta}-CD MPs) - to extend the delivery of 15-PGDH inhibitor, (+)SW033291, to over one week. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/456403v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@13aed1dorg.highwire.dtl.DTLVardef@1a541eaorg.highwire.dtl.DTLVardef@8a9fd5org.highwire.dtl.DTLVardef@1038a77_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Dogan, A. B., Rohner, N. A., Smith, J. N. P., Kilgore, J. A., Williams, N. S., Markowitz, S. D., von Recum, H. A., Desai, A. B.. 2021-08-15. Polymer microparticles prolong delivery of the 15-PGDH inhibitor SW033291. https://doi.org/10.1101/2021.08.15.456403

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