Cyclodextrin Polymer Preserves Sirolimus Activity and Local Persistence for Antifibrotic Delivery over the Time Course of Wound Healing.

Molecular Pharmaceutics
Nathan A RohnerHorst A von Recum

Abstract

Fibrosis and dysphagic stricture of the esophagus is a major unaddressed problem often accompanying endoscopic removal of esophageal cancers and precancerous lesions. While weekly injections of antiproliferative agents show potential for improved healing, repeated injections are unlikely clinically and may alternatively be replaced by creating an esophageal drug delivery system. Affinity-based polymers have previously shown success for continuous delivery of small molecules for weeks to months. Herein, we explored the potential of an affinity-based microparticle to provide long-term release of an antiproliferative drug, sirolimus. In molecular docking simulations and surface plasmon resonance experiments, sirolimus was found to have suitable affinity for beta-cyclodextrin, while dextran, as a low affinity control, was validated. Polymerized beta-cyclodextrin microparticles exhibited 30 consecutive days of delivery of sirolimus during in vitro release studies. In total, the polymerized beta-cyclodextrin microparticles released 36.9 mg of sirolimus per milligram of polymer after one month of incubation in vitro. Taking daily drug release aliquots and applying them to PT-K75 porcine mucosal fibroblasts, we observed that cyclodextr...Continue Reading

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Citations

Aug 7, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Nathan A RohnerHorst A von Recum
Mar 21, 2020·Pharmaceutics·Nathan A RohnerHorst A von Recum
May 23, 2020·Biomaterials Science·David A McBrideNisarg J Shah
May 23, 2020·International Journal of Molecular Sciences·Rebecca M HaleyEvon S Ereifej
Aug 28, 2020·Acta Biomaterialia·Alan Dogan, Horst von Recum

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