Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291

Pharmaceutics

Jessica A. Kilgore¹  Noelle S. Williams¹  Horst A. von Recum²  Alan B. Dogan²  Nathan A. Rohner²  Sanford D. Markowitz³  Julianne N. P. Smith³  Amar B. Desai³ 

[1] Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA;Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA;Department of Medicine and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA;

关键词: fibrosis;    15-PGDH;    SW033291;    cyclodextrin;    affinity;   

DOI  :  10.3390/pharmaceutics14010085

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown