Newly synthesized surfactants for surface mannosylation of respirable SLN assemblies to target macrophages in tuberculosis therapy

Maretti, Eleonora; Costantino, Luca; Buttini, Francesca; Rustichelli, Cecilia; Leo, Eliana Grazia; Truzzi, Eleonora; Iannuccelli, Valentina

doi:10.1007/s13346-018-00607-w

Cited by 45 publications

(46 citation statements)

References 52 publications

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“…TB is caused by Mycobacterium tuberculosis (Mtb) residing and surviving inside alveolar macrophages (AM). After being inhaled, Mtb reaches the alveoli, where it is phagocytosed by AM, a site difficult to be reached effectively by most antibiotics [2][3][4][5][6]. If the primary infection (pulmonary TB) is not completely eradicated, it can progress and disseminate into other organs (miliary TB).…”

Section: Introductionmentioning

confidence: 99%

“…Within this context, we previously developed respirable solid lipid nanoparticle assemblies (SLNas) loaded with rifampicin (RIF), a clinically useful first-line anti-TB drug, for an AM passive targeting [6,16]. Thereafter an AM active targeting to mannose receptors (MR), located on the macrophage membrane and overexpressed in case of Mtb-infection, was obtained by exploiting mannosylated SLNas.…”

Section: Introductionmentioning

confidence: 99%

“…The mannosylated SLNas demonstrated their ability to interact with MR on J774 and MH-S macrophage cell lines improving cell internalization ability in comparison with non-functionalized SLNas and bare RIF. Furthermore, the MR-specific binding was negligibly impaired by the protein/lipid corona layer formed around the nanoparticles upon their contact with a commercial substitute of the natural pulmonary surfactant [6,17].…”

Section: Introductionmentioning

confidence: 99%

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In Vivo Biodistribution of Respirable Solid Lipid Nanoparticles Surface-Decorated with a Mannose-Based Surfactant: A Promising Tool for Pulmonary Tuberculosis Treatment?

et al. 2020

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The active targeting to alveolar macrophages (AM) is an attractive strategy to improve the therapeutic efficacy of ‘old’ drugs currently used in clinical practice for the treatment of pulmonary tuberculosis. Previous studies highlighted the ability of respirable solid lipid nanoparticle assemblies (SLNas), loaded with rifampicin (RIF) and functionalized with a novel synthesized mannose-based surfactant (MS), both alone and in a blend with sodium taurocholate, to efficiently target the AM via mannose receptor-mediated mechanism. Here, we present the in vivo biodistribution of these mannosylated SLNas, in comparison with the behavior of both non-functionalized SLNas and bare RIF. SLNas biodistribution was assessed, after intratracheal instillation in mice, by whole-body real-time fluorescence imaging in living animals and RIF quantification in excised organs and plasma. Additionally, SLNas cell uptake was determined by using fluorescence microscopy on AM from bronchoalveolar lavage fluid and alveolar epithelium from lung dissections. Finally, histopathological evaluation was performed on lungs 24 h after administration. SLNas functionalized with MS alone generated the highest retention in lungs associated with a poor spreading in extra-pulmonary regions. This effect could be probably due to a greater AM phagocytosis with respect to SLNas devoid of mannose on their surface. The results obtained pointed out the unique ability of the nanoparticle surface decoration to provide a potential more efficient treatment restricted to the lungs where the primary tuberculosis infection is located.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In Vivo Biodistribution of Respirable Solid Lipid Nanoparticles Surface-Decorated with a Mannose-Based Surfactant: A Promising Tool for Pulmonary Tuberculosis Treatment?

et al. 2020

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“…An MMAD of around 5-7 µm and an FPF within 30% and 50% were determined. The SLN were mannosylated to improve their targeting ability, which was verified experimentally, with increased macrophage uptake (~80%) compared to non-functionalized SLN (~40%) [71,73]. Rifampicin was also the chosen antitubercular drug to encapsulate in polymer-glycerosomes, which showed to be more stable than conventional liposomes [74].…”

Section: Delivery Of Antibioticsmentioning

confidence: 89%

“…Very frequently, the developed carriers involve strategies of surface chemical functionalization, namely mannosylation. The rationale behind this approach is based on the fact that bacterial hosts, the macrophages, have several surface receptors that are likely to be used as therapeutic targets [70,71]. The mannose receptor is one of the main, which may provide a favorable interaction with some units and chemical groups present on the carriers' surface, including the mannose units, but also others like fucose and N-acetylglucosamine [72].…”

Section: Delivery Of Antibioticsmentioning

confidence: 99%

Multifunctional Nanocarriers for Lung Drug Delivery

Pontes

Grenha

2020

Nanomaterials

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Nanocarriers have been increasingly proposed for lung drug delivery applications. The strategy of combining the intrinsic and more general advantages of the nanostructures with specificities that improve the therapeutic outcomes of particular clinical situations is frequent. These include the surface engineering of the carriers by means of altering the material structure (i.e., chemical modifications), the addition of specific ligands so that predefined targets are reached, or even the tuning of the carrier properties to respond to specific stimuli. The devised strategies are mainly directed at three distinct areas of lung drug delivery, encompassing the delivery of proteins and protein-based materials, either for local or systemic application, the delivery of antibiotics, and the delivery of anticancer drugs—the latter two comprising local delivery approaches. This review addresses the applications of nanocarriers aimed at lung drug delivery of active biological and pharmaceutical ingredients, focusing with particular interest on nanocarriers that exhibit multifunctional properties. A final section addresses the expectations regarding the future use of nanocarriers in the area.

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