Polymeric nanoparticles improved Curcumin brain delivery and its therapeutic efficacy against intracerebral hemorrhage

Abstract

Background: Intracerebral hemorrhage (ICH) is a severe type of stroke. Ferroptosis is a new form of regulated cell death, which plays an indispensable role in the pathological process of ICH. Curcumin (Cur), a widespread phenolic compound, is derived from the rhizome of Curcuma longa. It could attenuate hematoma volume and neurological injury in ICH. Nevertheless, its poor solubility in water, low oral bioavailability and difficulty in transporting across physiological barriers led to poor efficacy. Polymer nanoparticles (NPs) are widely used drug delivery matrix material with good biocompatibility, which are reported to improve the bioavailability and pharmacokinetic profiles of drugs. In this study, we utilized NPs to encapsulate Cur and analyzed the effect of Cur-NPs on Cur brain delivery and its therapeutic efficacy against ICH. Results: The spherical Cur-NPs had a particle size 127.31±2.73 nm, a PDI of 0.21±0.01 and a zeta potential of -0.25±0.02 mV. Cur-NPs could draw into Madin-Darby canine kidney (MDCK) cells through a number of nonspecific endocytosis mechanisms, mainly mediated via clathrin and plasma membrane microcapsules. Moreover, Cur-NPs tended to accumulate in the endoplasmic reticulum and lysosome. In a zebrafish model, Cur-NPs could transport across physiological barriers. In a C57BL/6 mice model, we found that Cur-NPs had more desirable improvements in Cur accumulation within the plasma and brain. Importantly, in an ICH mouse model, we confirmed that Cur-NPs were an effective treatment for ICH. Finally, Cur-NPs effectively inhibited ferroptosis caused by erastin in HT22 mouse hippocampal cells. Conclusion: Cur-NPs represent a potentially effective strategy to enhance Cur brain delivery and therapeutic efficacy in the treatment of ICH.