RT Journal Article T1 Design and in vitro assessment of chitosan nanocapsules for the pulmonary delivery of rifabutin A1 Valverde-Fraga, Lorena A1 Haddad, Razan A1 Alrabadi, Nasr A1 Sánchez Poza, María Sandra A1 Remuñán López, Carmen A1 Csaba, Noemi Stefania K1 Chitosan nanocapsules K1 Rifabutin K1 PEG-stearate K1 Lecithin K1 Antituberculosis treatment AB Tuberculosis (TB) is a life-threatening disease and a main cause of death worldwide. It mainly affects the lungs, and it is attributed to the infection with Mycobacterium tuberculosis (MTB). Current treatments consist of the oral administration of combinations of antibiotics including rifabutin, in high doses and for long periods of time. These therapeutic regimens are associated with many side effects and high rates of drug resistance. To overcome these problems, this study aims at developing a nanosystem for the improved delivery of antibiotics, with potential application in pulmonary delivery.Chitosan-based nanomaterials are widely used in biomedical applications, due to their biodegradability and biocompatibility, as well as their potential antimicrobial effects and lack of toxicity. In addition, this polymer is particularly attractive for mucosal delivery due to its bioadhesive properties. Therefore, the structure of the proposed nanocarrier consists of a chitosan shell and a lipid core with a combination of different oils and surfactants to allow optimal association of the hydrophobic drug rifabutin. These nanocapsules were characterized in terms of size, polydispersity index, surface charge, morphology, encapsulation efficiency and biological stability. The release kinetics of the drug-loaded nanostructures was evaluated in simulated lung media. Moreover, in vitro studies in different cell models (A549 and Raw 264.7 cells) demonstrated the safety of the nanocapsules as well as their efficient internalization. An antimicrobial susceptibility test was performed to evaluate the efficacy of the rifabutin-loaded nanocapsules against Mycobacterium phlei. This study indicated complete inhibition for antibiotic concentrations within the expected susceptibility range of Mycobacterium (≤ 0.25–16 mg/L) PB Elsevier SN 0928-0987 YR 2023 FD 2023-05-31 LK http://hdl.handle.net/10347/31219 UL http://hdl.handle.net/10347/31219 LA eng NO European Journal of Pharmaceutical Sciences 187 (2023) 106484 NO This work has received financial support from the Xunta de Galicia (Centro singular de investigación de Galicia, accreditation 2019–2022); Competitive Reference Groups, ED431C 2021/17-FEDER) and Ministerio de Ciencia e Innovación, Gobierno de España (PID2019-107500RB-I00) DS Minerva RD 30 abr 2026