In Vitro Release of Curcumin from Polymeric Nanoparticles Using Two-Phase System

In vitro models to measure the release of hydrophobic compounds from polymeric nanocarriers are investigated and compared. The release models consist of a two-phase system. An aqueous solution in the bottom layer contains suspended polymeric nanoparticles encapsulating a hydrophobic compound. A water-immiscible organic solvent of lower density is used to extract the compound from the aqueous phase. This system overcomes the solubility limitation of hydrophobic compounds in aqueous solutions. It provides a faster and more convenient way to characterize the in vitro release of hydrophobic compounds from nanoparticles. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles with negative surface charges and poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles with neutral surface brushes encapsulating curcumin were used in this study. Three types of interfaces were tested: (1) liquid-liquid interface, (2) phospholipid packed interface, and (3) dialysis membrane interface. In the first case, relatively quicker release of curcumin from both types of polymeric nanoparticles was recorded, which was mainly caused by the direct contact of particles with the organic solvent at the liquid-liquid interface. The release was independent of solution pH. In the second case, monolayers of amphiphilic molecules with different packing strength (such as phospholipids with and without cholesterol and PEGylated phospholipids) were formed at the liquid-liquid interface to depict biological barriers. The self-assembled monolayers at the interface did not provide a sufficient energy barrier to decrease the collision rate of the particles occurring at the liquid-liquid interface, and the release rate of curcumin was similar as the one measured using the first system. The third in vitro release model with a dialysis membrane at the interface using a custom-designed glass cell completely prevented the contact of particles with the organic solvent, resulting in a diffusion-controlled drug release profile of curcumin. The mathematical 1D diffusion analysis was applied to reveal the sensitivity of diffusivity of the compound in the organic solvent and partition coefficient of the compound in each phase of the solutions.