Chitosan-Based Nanocapsules as a Delivery System of Hydrophobic Carnosic Acid, A Model Neuroprotective Drug

Joanna Odrobińska-Baliś,1 Magdalena Procner,1,2 Kinga Krużel,1 Magdalena Regulska,2 Monika Leśkiewicz,2 Dorota Duraczyńska,1 Szczepan Zapotoczny,3 Władysław Lasoń,2 Krzysztof Szczepanowicz1 1Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Krakow, Poland; 2Maj Institute of Pharmacology Polish Academy of Science, Krakow, Poland; 3Faculty of Chemistry, Jagiellonian University, Krakow, PolandCorrespondence: Joanna Odrobińska-Baliś, Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezpominajek 8, Krakow, 30-239, Poland, Tel +48 12 6395128, Email [email protected]: Since the population of Europe is rapidly aging, the number of cases of neurodegenerative diseases sharply increases. One of the most significant limitations of current neurodegenerative disease treatment is the inefficient delivery of neuroprotective drugs to the affected part of the brain. One of the promising methods to improve the pharmacokinetic and pharmacodynamic properties of antioxidants is their encapsulation in nanocarriers.Materials and Methods: Encapsulation of carnosic acid into a chitosan-based nanoparticle system with ultrasound-assisted emulsification process was developed. The physicochemical properties (size, stability, concentration of nanoparticles) of obtained nanocapsules were analyzed. Also, the cytotoxicity and neuroprotective effect in SH-SY5Y cells exposed to toxic concentration of H2O2 of the obtained nanoparticles were evaluated in vitro.Results and Discussion: The capsules with diameters between 90 and 150 nm and long-term stability were obtained. Cytotoxicity tests of empty capsules indicate that observed toxic effects were concentration dependent and lower concentrations (dilution above 500×) can be considered as safe for tested cells. Our study also indicates that encapsulation of carnosic acid decreased the cytotoxicity of empty nanocapsules and can efficiently protect SH-SY5Y cells from factors causing cell destruction. In addition, the neuroprotective efficacy of carnosic acid loaded nanocapsules was also demonstrated in SH-SY5Y cells exposed to toxic concentration of H2O2. The designed nanoparticles appear to possess sufficient biocompatibility to deserve their further evaluation in in vivo models.Keywords: polysaccharide nanocapsules, modified chitosan, carnosic acid, neuroprotection