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Eur J Pharm Sci. 2018 Mar 1;114:103-113. doi: 10.1016/j.ejps.2017.12.006. Epub 2017 Dec 8.

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

Author information

1
i3S, Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB, Instituto de Engenharia Biomédica, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; ICBAS, Instituto Ciências Biomédicas Abel Salazar, Rua Jorge Viterbo Ferreira 228, 4050-223 Porto, Portugal.
2
i3S, Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; INEB, Instituto de Engenharia Biomédica, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.
3
CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra, Portugal.

Abstract

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.

KEYWORDS:

Alveolar macrophage; Macrophage nanoparticle uptake; Mannose functionalization; Solid lipid nanoparticles

PMID:
29229273
DOI:
10.1016/j.ejps.2017.12.006
[Indexed for MEDLINE]

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