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Aquaporins (AQPs), members of the water-channel protein family, are highly expressed in brain tissue especially in astrocytic end-feet. They are important players for water hemostasis during development of cytotoxic as well as vasogenic edema. Increased expression of AQPs is important in pathophysiology of neurological diseases such as neuroinflammation and ischemia. Unfortunately, there are a few pharmacological inhibitors of AQP4 with several side effects limiting their translation as a drug for use in clinical conditions. Another therapeutic approach is using antisense oligonucleotides (ASOs) to block AQP4 activity. These are short, synthetic, modified nucleic acids that bind RNA to modulate its function. However, they cannot pass the blood brain barrier (BBB). To overcome this obstacle we designed a nanoparticulate system made up of chitosan nanoparticles surface modified with PEG and conjugated with monoclonal anti transferrin receptor-1 antibody via streptavidin-biotin binding. The nanocarrier system could be targeted to the transferrin receptor-1 at the brain endothelial capillaries through monoclonal antibodies. It is hypothesized that the nanoparticles could pass the BBB via receptor mediated transcytosis and reach brain parenchyma. Particle size, zeta potential, loading capacity and release profiles of nanoparticles were investigated. It was observed that all types of chitosau (CS) nanoparticles had positive zeta potential values and nanoparticle particle size distribution varied between 100 and 800 nm. The association efficiency of ASOs into the nanoparticles was between 80–97% and the release profiles of the nanoparticles exhibited an initial burst effect followed by a controlled release. The results showed that the designed chitosan based nanocarriers could be a promising carrier system to transport nucleic acid based drugs to brain parenchyma This study is supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project Number: 110S460) SI

In this work, PLGA nanoparticles were prepared by an emulsification-diffusion technique. The main objective was to optimize the preparation of formulations by evaluating the influence of the technological parameters on the physicochemical properties of PLGA nanoparticles. The effects of variations in polymer and emulsifier concentrations, and homogenization duration, rate and type on the particle size distribution, surface charge and morphology of nanoparticles were assessed. The smallest nanoparticles (177.53 +/- 2.78 nm) were obtained with a 2% PLGA (w/v) concentration in the organic phase and 3% PVA (w/v) in the aqueous phase and were prepared by an emulsification-diffusion method via ultrasonic homogenization at a power of 80 W applied for 30 s. It was observed that nanoparticles prepared by Ultra Turrax were more spherical but larger. In addition, increasing the PVA concentration in the aqueous phase, increasing the PLGA concentration in the organic phase and increasing the homogenization rate decreased the zeta potential values of PLGA nanoparticles.