Resumen del trabajo presentado a la 4th SBAN Spanish Conference on Biomedical Applications of Nanomaterials (SBAN), celebrada online del 2 al 4 de junio de 2021. ; This work was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 842652. ; Peer reviewed
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).
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—ProgramaEstatal de Investigación, Desarrollo e InnovaciónOrientada 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). The authors also acknowledge José Antonio Ainsa and Ainhoa Lucía for the fruitful discussions as well as Rodrigo Fernandez-Pacheco and Alfonso Ibarra from Advanced Microscopy Laboratories of the Universidad de Zaragoza and Iñigo Echaniz for their technical support. The costs to publish in open access have been covered by funds from NAREB Project (see before) ; We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).
The appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial-loaded nanocarriers are avidly taken up by macrophages, the main cells hosting Mycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment. ; This work was supported by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement No. 842652, the Spanish MICINN projects (Grant Nos. BIO2017-84246-C2-1-R, SAF2017-84839-C2-1-R, and CTQ2015-66869-P), and by the Gobierno de Aragón (Diputación General de Aragón–Fondo Social Europeo). R.M.-R. acknowledges MICINN for funding through the Ramón y Cajal Program (Grant No. RYC-2013-12570). H.S.-C. and A.C.M.-P. are grateful for FPU predoctoral contracts from Ministerio de Educación Cultura y Deporte (Spain) and M.A. is grateful for a predoctoral contract from Gobierno de Aragón (Diputación General de Aragón–Fondo Social Europeo). ; Peer reviewed