Supramolecular Arrangement of Doxycycline with Sulfobutylether-β-Cyclodextrin: Impact on Nanostructuration with Chitosan, Drug Degradation and Antimicrobial Potency

Doxycycline (DX) is a well-established and broad-spectrum antimicrobial drug. However, DX has drawbacks, such as physicochemical instability in aqueous media and bacterial resistance. The inclusion of drugs in cyclodextrin complexes and their loading into nanocarriers can overcome these limitations. Thus, we studied the DX/sulfobutylether-β-CD (SBE-β-CD) inclusion complex for the first time and used it to reticulate chitosan. The resulting particles were evaluated by their physicochemical characteristics and antibacterial activity. DX/SBE-β-CD complexes were characterized by nuclear magnetic resonance, infrared spectroscopy, thermal analysis, X-ray diffraction, and scanning electron microscopy (SEM), whereas DX-loaded nanoparticles were characterized by dynamic light scattering, SEM, and drug content. The partial inclusion of the DX molecule in CD happened in a 1:1 proportion and brought increased stability to solid DX upon thermal degradation. Chitosan-complex nanoparticles measured approximately 200 nm, with a narrow polydispersity and particles with sufficient drug encapsulation for microbiological studies. Both formulations preserved the antimicrobial activity of DX against Staphylococcus aureus, whereas DX/SBE-β-CD inclusion complexes were also active against Klebsiella pneumoniae, indicating the potential use of these formulations as drug delivery systems to treat local infections.Fil: Carvalho Feitosa, Renata. Universidade Estadual de Campinas; BrasilFil: Souza Ribeiro Costa, Juliana. Universidade Estadual de Campinas; BrasilFil: van Vliet Lima, Marcelo. Universidade Estadual de Campinas; BrasilFil: Sawa Akioka Ishikawa, Elina. Universidade Estadual de Campinas; BrasilFil: Cogo Müller, Karina. Universidade Estadual de Campinas; BrasilFil: Bonin Okasaki, Fernando. Universidade Estadual de Campinas; BrasilFil: Sabadini, Edvaldo. Universidade Estadual de Campinas; BrasilFil: Garnero, Claudia. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Lavayen, Vladimir. Universidade Federal do Rio Grande do Sul; BrasilFil: da Silva Júnior, Arnóbio Antônio. Universidade Federal do Rio Grande do Norte; BrasilFil: Oliveira Nascimento, Laura. Universidade Estadual de Campinas; Brasi