Physical stability and in vivo brain delivery of polymeric ibuprofen nanoparticles fabricated by flash nanoprecipitation

Abstract

Ibuprofen (IBP), a common non-steroidal anti-inflammatory drug (NSAID) with a log P of 3.51, has been shown to possess potential benefit in the treatment of Alzheimer’s disease. However, the bioavailability of IBP to the brain is poor, which can be linked to its extensive binding to plasma proteins in the blood. This study aimed to evaluate the nanoparticle production of IBP by flash nanoprecipitation (FNP) technology, and to determine whether the nanoparticles prepared by FNP could enhance the delivery of IBP into the brain. Polymeric IBP nanoparticles were prepared with poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) diblock copolymer as stabilizer under optimized conditions using a four-stream multi-inlet vortex mixer (MIVM). The optimized nanoparticles displayed a mean particle size of around 50 nm, polydispersity index of around 0.2, drug loading of up to 30% and physical stability of up to 34 days. In-depth surface characterization using zeta potential measurement, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) showed that the surfaces of these nanoparticles were covered with the hydrophilic PEG groups from the diblock copolymer. In vivo brain uptake study of the IBP nanoparticles indicated that the particles, when coated with polysorbate 80, displayed an enhanced brain uptake. However, the extent of brain uptake enhancement appeared limited, possibly due to a rapid release of IBP from the nanoparticles into the blood stream following intravenous administration.