Controlling properties and cytotoxicity of chitosan nanocapsules by chemical grafting

The tunability of the properties of chitosan-based carriers opens new ways for the application of drugs with low water-stability or high adverse effects. In this work, the combination of a nanoemulsion with a chitosan hydrogel coating and the following poly (ethylene glycol) (PEG) grafting is proven to be a promising strategy to obtain a flexible and versatile nanocarrier with an improved stability. Thanks to chitosan amino groups, a new easy and reproducible method to obtain nanocapsule grafting with PEG has been developed in this work, allowing a very good control and tunability of the properties of nanocapsule surface. Two different PEG densities of coverage are studied and the nanocapsule systems obtained are characterized at all steps of the optimization in terms of diameter, Z potential and surface charge (amino group analysis). Results obtained are compatible with a conformation of PEG molecules laying adsorbed on nanoparticle surface after covalent linking through their amino terminal moiety. An improvement in nanocapsule stability in physiological medium is observed with the highest PEG coverage density obtained. Cytotoxicity tests also demonstrate that grafting with PEG is an effective strategy to modulate the cytotoxicity of developed nanocapsules. Such results indicate the suitability of chitosan as protective coating for future studies oriented toward drug delivery.Authors would like to acknowledge the public funding from Fondo Social de la DGA (grupos DGA), Ministerio de la Economía y Competitividad del Gobierno de España for the public founding of ProyectosI+D+i—Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad (project n. SAF2014-54763-C2-2-R), the European Seventh Framework Program (NAREB Project 604237), LLP/Erasmus fellowship 2013/2014, INA fellowship “Iniciación a la Investigación” 2014 and 2015, and the European Union’s Horizon 2020 research and innovation program for MCSA Fellowship (Grant Agreement No. 660228).We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)