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. Although 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, β-CD microparticles (β-CD MPs)—to extend the delivery of the 15-PGDH inhibitor, (+)SW033291, to over one week.
Highlights
We propose the use of crosslinked cyclodextrin microparticles (CD MPs) as a vehicle for the sustained release of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor (+)SW033291
Utilizing two methods ofBefore affinity prediction—docking simulations and quantitative structure delivery activity relabeginning in vitro studies, we confirmed that a cyclodextrin plattionship (QSAR)—we foundwith that(+)SW033291’s
Docking simulations revealed that the central moiety methods of affinity prediction—docking simulations and quantitative structure activity which binds with cyclodextrin
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In a normal wound healing response, fibroblast activity is essential for remodeling the extracellular matrix (ECM) after injury. In instances of unbalanced or uncontrolled tissue remodeling, the excessive deposition of ECM components results in fibrosis, which is a common pathological outcome of several chronic inflammatory diseases [1]. Connective tissue replaces parenchymal tissue, rendering the inflicted tissue partially or completely inflamed or damaged. The most common manifestations of fibrotic damage can be seen in chronic diseases such as end-stage liver failure, kidney disease, heart failure, and idiopathic pulmonary fibrosis (IPF) [2]
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