Author(s): Martin, Victor ; Ribeiro, Isabel A. C. ; Alves, Marta M. ; Gonçalves, Lídia ; Almeida, António José ; Grenho, Liliana ; Fernandes, Maria H. ; Santos, Catarina F. ; Gomes, Pedro S. ; Bettencourt, Ana
Date: 2019
Persistent ID: http://hdl.handle.net/10451/62014
Origin: Repositório da Universidade de Lisboa
Subject(s): Chitosan; Minocycline; Intracellular-target delivery; Perioceutics; Inflammation; Periodontitis
Periodontal diseases remain a challenge due to a complex interplay of factors involving a chronic inflammatory activation and bacteria internalization in periodontal cells. In this work, chitosan-nanoparticles loaded with minocycline (MH-NPs), a tetracycline with antimicrobial and anti-inflammatory effects, were developed for in situ delivery in the periodontal milieu aiming to improve drug effectiveness. A general cytocompatibility evaluation and a detailed approach to address the cellular uptake process, trafficking pathways and the modulation of relevant inflammatory gene expression was conducted using human gingival fibroblasts. Results show that MH-NPs with an adequate cytocompatible profile can be internalized by distinct endocytic processes (macropinocytosis and clathrin-mediated endocytosis). The ability to modulate autophagy with the delivery within the same endosomal/lysosomal pathway as periodontal pathogens was observed, which increases the intracellular drug effectiveness. Porphyromonas gingivalis LPS-stimulated cultures, grown in the presence of MH-NPs, were found to express significantly reduced levels of inflammation-related markers (IL-1b, TNFα, CXCL-8, NFKB1). These nanoparticles can be potentially used in periodontal disease treatment conjoining the ability of intracellular drug targeting with significant anti-inflammatory effects.
