Curcumin is a bioactive molecule extracted from Turmeric roots that has been recognized to possess a wide variety of important biological activities. Despite its great pharmacological activities, curcumin is highly hydrophobic, which results in poor bioavailability. We have formulated this hydrophobic compound into stable polymeric nanoparticles (nano-curcumin) to enhance its oral absorption. Pharmacokinetic analysis after oral delivery of nano-curcumin in mice demonstrated approximately 20-fold reduction in dose requirement when compared to unformulated curcumin to achieve comparable plasma and central nervous system (CNS) tissue concentrations. This investigation corroborated our previous study of curcumin functionality of attenuating opioid tolerance and dependence, which shows equivalent efficacy of low-dose (20mg/kg) nano-curcumin and high-dose (400mg/kg) pure curcumin in mice. Furthermore, the highly selective and validated liquid chromatography-mass spectrometry (LC-MS) method was developed to quantify curcumin glucuronide, the major metabolite of curcumin. The results suggest that the presence of curcumin in the CNS is essential for prevention and reversal of opioid tolerance and dependence.

We report on the precise manipulation of the fine structures of toroidal-spiral particles (TSPs) generated by a self-assembly process of droplet sedimentation at low Reynolds numbers in a miscible bulk solution followed by solidification. The biocompatible polymeric TSP can serve as a device for drug delivery and in vivo therapeutic cell expansion, activation, and delivery, for which highly tunable and reproducible structures are essential to design dosages and release kinetics. TSP formation can be divided into two stages: initial infusion of the drop vs its subsequent sedimentation, deformation, and entrainment of the surrounding bulk solution. The infusion rate affects the drop shape and tail length. These two features represent crucial initial conditions for subsequent shape evolution, which determines the overall morphology of the TSP and fine structure of the internal channel. Our computer simulations of drop dynamics add a new capability to the swarm-of-Stokeslets technique: unequal viscosities of the drop and bulk phases (i.e., non-unit viscosity ratio). During sedimentation, the density difference between the droplet and the bulk solution played a more pronounced role than the viscosity ratio, which was revealed both by experimental observations and numerical simulations. Understanding the fundamental hydrodynamics and developing a flow map will ultimately aid in the design of TSPs with tunable empty channels toward drug delivery and cell encapsulation.