Solid Lipid Nanoparticle assemblies (SLNas) for an anti-TB inhalation treatment⿿A Design of Experiments approach to investigate the influence of pre-freezing conditions on the powder respirability

Maretti, Eleonora; Rustichelli, Cecilia; Romagnoli, Marcello; Balducci, Anna; Buttini, Francesca; Sacchetti, Francesca; Leo, Eliana Grazia; Iannuccelli, Valentina

doi:10.1016/j.ijpharm.2016.07.062

Cited by 42 publications

(23 citation statements)

References 39 publications

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“…Dialysis time was selected in preliminary studies as the best compromise between drug retaining within SLNas and the surfactant removal. Then, the samples were water diluted 1:55, rapidly frozen at −70 °C in a dry ice/acetone cooling bath, and then freeze-dried (Lio 5P, CinquePascal, Milan, Italy), to obtain a final powder according to the method previously optimized [34].…”

Section: Methodsmentioning

confidence: 99%

“…Within this context, respirable Solid Lipid Nanoparticle assemblies (SLNas) loaded with rifampicin, a clinically useful anti-tuberculosis drug, were previously produced as inhaled pulmonary tuberculosis treatment using DPI device. To this aim, accepted excipients for DPI formulations were processed through an optimized methodology that avoids organic solvents [33,34]. The prototypes were functionalized by means of newly synthesized mannosylated surfactants as AM receptor-specific targeting agents anchored on SLNas surface without the need of chemical reactions [5].…”

Section: Introductionmentioning

confidence: 99%

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The Impact of Lipid Corona on Rifampicin Intramacrophagic Transport Using Inhaled Solid Lipid Nanoparticles Surface-Decorated with a Mannosylated Surfactant

et al. 2019

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The mimicking of physiological conditions is crucial for the success of accurate in vitro studies. For inhaled nanoparticles, which are designed for being deposited on alveolar epithelium and taken up by macrophages, it is relevant to investigate the interactions with pulmonary surfactant lining alveoli. As a matter of fact, the formation of a lipid corona layer around the nanoparticles could modulate the cell internalization and the fate of the transported drugs. Based on this concept, the present research focused on the interactions between pulmonary surfactant and Solid Lipid Nanoparticle assemblies (SLNas), loaded with rifampicin, an anti-tuberculosis drug. SLNas were functionalized with a synthesized mannosylated surfactant, both alone and in a blend with sodium taurocholate, to achieve an active targeting to mannose receptors present on alveolar macrophages (AM). Physico-chemical properties of the mannosylated SLNas satisfied the requirements relative to suitable respirability, drug payload, and AM active targeting. Our studies have shown that a lipid corona is formed around SLNas in the presence of Curosurf, a commercial substitute of the natural pulmonary surfactant. The lipid corona promoted an additional resistance to the drug diffusion for SLNas functionalized with the mannosylated surfactant and this improved drug retention within SLNas before AM phagocytosis takes place. Moreover, lipid corona formation did not modify the role of nanoparticle mannosylation towards the specific receptors on MH-S cell membrane.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Impact of Lipid Corona on Rifampicin Intramacrophagic Transport Using Inhaled Solid Lipid Nanoparticles Surface-Decorated with a Mannosylated Surfactant

et al. 2019

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“…As the controls, non-mannosylated SLNas/ST and SLNas/F127 samples were obtained by using 0.2% ST or 1% F127, respectively, as emulsifier. After cooling in ice bath, SLNas samples were purified by dialysis, frozen at −70 • C, and freeze-dried (Lio 5P, CinquePascal, Milan, Italy) according to the method previously adopted [23]. All the samples were used in a labeled form by dissolving preventively 0.2% IR-780 in the melted PA before the melt emulsification process.…”

Section: Slnas Preparationmentioning

confidence: 99%

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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“…The results gained showed a signi icant impact exerted by quick freezing combined with sample dilution before pre-freezing step without using cryprotectant on the respirable powder ef iciency. The respirable powder achieved was >50% (Maretti, 2016). Recently, researchers have tried and have been successful in formulating hybrid solid lipid nanoparticles, i.e.…”

Section: Lyophilizationmentioning

confidence: 99%

Recent updates on dry powder for inhalation for pulmonary drug delivery systems

Deshkar

Vas

2019

ijrps

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Pulmonary drug delivery system is an attractive and most promising approach which is gaining great impetus for the delivery of various therapeutic agents which includes administration of proteins and peptides, agents for the treatment of tuberculosis, asthma, diabetes chronic obstructive pulmonary diseases (COPD), various fungal infections, cancer, etc. This route has gained great importance due to its large surface and the absorptive area, which can potentially bypass the hepatic first-pass metabolism. The dawn of nanotechnology has brought a lot of advancement in the pre-existing formulation aspect with respect to reducing the systemic toxicity and dosing, specific targeting and enhanced efficiency of the treatment. This review reflects on the basics of pulmonary drug delivery, various formulations options available for administration via dry powder inhalers and advances in the same.

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Solid Lipid Nanoparticle assemblies (SLNas) for an anti-TB inhalation treatment⿿A Design of Experiments approach to investigate the influence of pre-freezing conditions on the powder respirability

Cited by 42 publications

References 39 publications

The Impact of Lipid Corona on Rifampicin Intramacrophagic Transport Using Inhaled Solid Lipid Nanoparticles Surface-Decorated with a Mannosylated Surfactant

The Impact of Lipid Corona on Rifampicin Intramacrophagic Transport Using Inhaled Solid Lipid Nanoparticles Surface-Decorated with a Mannosylated Surfactant

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

Recent updates on dry powder for inhalation for pulmonary drug delivery systems

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