RT Journal Article T1 Design, Optimization, and Characterization of Lactoferrin-Loaded Chitosan/TPP and Chitosan/Sulfobutylether-β-cyclodextrin Nanoparticles as a Pharmacological Alternative for Keratoconus Treatment A1 Varela Fernández, Rubén A1 García Otero, Xurxo A1 Díaz Tomé, Victoria A1 Regueiro, Uxía  A1 López López, Maite A1 González Barcia, Miguel A1 Lema Gesto, María Isabel A1 Otero Espinar, Francisco Javier K1 Nanoparticles K1 Chitosan K1 Sulfobutylether-β-cyclodextrin K1 Tripolyphosphate K1 Lactoferrin K1 Topical ophthalmic administration K1 Protein nanocarriers K1 Keratoconus AB This research study describes the design, optimization, and characterization of two different types of chitosan-based nanoparticles as novel drug delivery systems of a protein drug, lactoferrin. A preclinical consistent base was obtained for both nanosystems, being considered as the first pharmacological treatment for keratoconus as an alternative to current invasive clinical methods. Both types of nanoparticles were obtained via the ionotropic gelation technique. The size and morphology of the nanoparticles were studied as a function of the preparation conditions. A mean size of 180.73 ± 40.67 nm, a size distribution [polydispersity index (PDI)] of 0.170 ± 0.067, and positive ζ-potential values, ranging from 17.13 to 19.89 mV, were achieved. Lactoferrin was successfully incorporated into both types of nanocarriers. In vitro release profiles showed a lactoferrin enhanced, prolonged, and controlled delivery from the polymeric matrix. These formulations also demonstrated no stability or cytotoxicity problems, as well as appropriate mucoadhesive properties, with a high permanence time in the ocular surface. Thus, both types of nanoparticles may be considered as nanocarriers for the controlled release of lactoferrin as novel topical ophthalmic drug delivery systems. PB American Chemical Society YR 2021 FD 2021 LK https://hdl.handle.net/10347/45963 UL https://hdl.handle.net/10347/45963 LA eng NO ACS Appl. Mater. Interfaces 2021, 13, 3, 3559–3575 NO This document is the unedited Author’s version of a Submitted Manuscript subsequently accepted for publication in ACS Applied Materials & Interfaces, copyright © 2021 American Chemical Society. To access the final published article, see: https://doi.org/10.1021/acsami.0c18926 NO R.V.-F. and X.G.-O. acknowledge the financial support of the FIDIS (Health Research Institute of Santiago de Compostela Foundation). Similarly, U.R. and M.L.L. acknowledge the support from Xunta de Galicia (Galician Innovation Agency GAIN: IN607A2018/3) and the Spanish Research Network on Cerebrovascular Diseases INVICTUS PLUS (RD16/0019) fellowships. This project was awarded a grant from the Spanish Ministry of Economy and Competitiveness (Instituto de Salud Carlos III: PI18/00159), and partially supported by the Spanish Ministry of Science, Innovation and Universities (RTI2018-099597-B-100). DS Minerva RD 24 abr 2026