Partial correction of cystic fibrosis defects with PLGA nanoparticles encapsulating curcumin

摘要

Cystic fibrosis (CF) is a common life threatening genetic disease (incidence: ～1 in 2500 live births). CF is caused by mutations in CFTR, a chloride channel involved in epithelial secretion of fluid and electrolytes. The most common mutation entails the deletion of a phenylalanine in position 508 that causes protein misfolding and abnormal CFTR processing. The ΔF508 mutation accounts for approximately 70% of all CF alleles, and about 90% of CF patients carry at least one copy of ΔF508 CFTR. Curcumin, a natural constituent of Curcuma longa (turmeric spice), is a nontoxic low-affinity SERCA (sarco (endo)plasmic reticulum calcium ATPase) pump inhibitor thought to permit ΔF508 CFTR escape from the ER. The compound has been shown to be capable of correcting the defect in cell lines and mice expressing ΔF508 CFTR. In this work, poly lactic-co-glycolic acid (PLGA) nanoparticles encapsulating curcumin were synthesized and used to treat two different CF mouse strains in an effort to correct the defects associated with CF by improving bioavailability of the compound, which has previously been a challenge in treatment with curcumin. Our results suggest that oral administration of PLGA nanoparticles encapsulating curcumin enhances the effects of curcumin therapy in CF mice, as compared to delivery of nonencapsulated curcumin.