Functionalized rifampicin-loaded nanostructured lipid carriers enhance macrophages uptake and antimycobacterial activity

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 175; pp. 306 - 313
• Main Authors: Carneiro, Simone Pinto, Carvalho, Karen Vitor, de Oliveira Aguiar Soares, Rodrigo Dian, Carneiro, Cláudia Martins, de Andrade, Milton Hércules Guerra, Duarte, Rafael Silva, dos Santos, Orlando David Henrique
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2019
• Subjects: Macrophages uptake; Modified-tuftsin; Nanostructured lipid carriers; Rifampicin; Tuberculosis; Nanostructured lipid carriers; Rifampicin; Tuberculosis; Macrophages uptake; Modified-tuftsin
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2018.12.003

[Display omitted] •A tuftsin-modified peptide (pTUF-OA) was successfully synthesized.•Rifampicin nanostructured lipid carriers were functionalized with pTUF-OA (NP-pRIF).•NP-pRIF presented a controlled drug release profile and non-cytotoxicity potential.•NP-pRIF was significantly more taken up by cells than naked nanoparticles.•NP-pRIF was 2-fold more effective against M. tuberculosis than free rifampicin. Tuberculosis is an infectious bacterial disease that causes millions of deaths worldwide. Current treatment recommended by WHO is effective, however it is an extensive and arduous process associated to severe adverse effects, which induces a low patient compliance and the emerging of multidrug resistant tuberculosis. Thus, as a main goal of this study, rifampicin nanoparticles were surface functionalized with a tuftsin-modifed peptide to selectively recognize receptors located on infected alveolar macrophages, enhancing nanoparticles uptake by these cells and improving antimycobacterial activity. A tuftsin-based modified peptide was synthesized and successfully attached to nanoparticles interface (NP-pRIF). In parallel, nanoparticles without peptide were also developed for comparison (NP-RIF). Physicochemical characterization demonstrated that stable and monodisperse nanodelivery systems were obtained, with a controlled drug release profile and non-cytotoxic potential. Moreover, nanoparticles containing peptide were significantly more internalized by macrophages than nanoparticles without peptide over a wide range of time. Both nanoparticles were 2-fold more effective against M. tuberculosis than free rifampicin, suggesting NP-pRIF as a promising strategy for the management of tuberculosis treatment.