Mannose-functionalized solid lipid nanoparticles are effective in targeting alveolar macrophages

• Published in: European journal of pharmaceutical sciences 2018-03, Vol.114, p.103-113
• Main Authors: Costa, Ana, Sarmento, Bruno, Seabra, Vítor
• Format: Article
• Language: English
• Subjects: Alveolar macrophage; Macrophage nanoparticle uptake; Mannose functionalization; Solid lipid nanoparticles
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2017.12.006

Mannose receptor is highly expressed on alveolar macrophages, being a potential target to promote the specific local drug delivery of anti-tuberculosis agents through the use of functionalized nanocarriers. In this work, isoniazid (Isn)-loaded solid lipid nanoparticles (SLN), reinforced with stearylamine (SA) were produced by double emulsion technique and further surface-functionalized with mannose in a straightforward chemical approach. Upon pre-formulation assessment, SLN close to 500 nm average size, positively charged and with association efficiency of ISN close to 50% were obtained. Functionalization with mannose was performed after SLN production and confirmed by Fourier transform infrared spectroscopy (FTIR). Both functionalized and non-functionalized SLN demonstrated to devoid of toxicity when tested in human lung epithelial cell line (NCI-H441) and differentiated THP-1 (dTHP-1), reducing the intrinsic cytotoxicity of Isn when incorporated into SLN. Uptake studies were conducted on same macrophage-like cells and the results showed that fluorescent mannosylated SLN (M-SLN) were more efficient in be internalized comparatively to SLN. Moreover, the uptake of M-SLN was reduced when cells were pre-incubated with mannose, demonstrating the receptor-dependence internalization of functionalized SLN. These functionalized nanocarriers may represent a useful platform to target alveolar macrophages for delivering anti-infective drugs. [Display omitted]