Dry-Powder Inhaler Formulation of Rifampicin: An Improved Targeted Delivery System for Alveolar Tuberculosis

Rawal, Tejal; Kremer, Laurent; Halloum, Iman; Butani, Shital

doi:10.1089/jamp.2017.1379

Cited by 21 publications

(9 citation statements)

References 32 publications

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“…In this experiment, the angle of repose of SCU@CD-MOF was determined by the fixed cone method 45 , 46 , 47 . Two funnels with a diameter of 7.0 cm were taken in series on an iron stand.…”

Section: Methodsmentioning

confidence: 99%

Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery

Zhao

Guo

Wang

et al. 2020

Acta Pharmaceutica Sinica B

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It is essential to develop new carriers for laryngeal drug delivery in light of the lack of therapy in laryngeal related diseases. When the inhalable micron-sized crystals of γ -cyclodextrin metal-organic framework (CD-MOF) was utilized as dry powder inhalers (DPIs) carrier with high fine particle fraction (FPF), it was found in this research that the encapsulation of a glycoside compound, namely, scutellarin (SCU) in CD-MOF could significantly enhance its laryngeal deposition. Firstly, SCU loading into CD-MOF was optimized by incubation. Then, a series of characterizations were carried out to elucidate the mechanisms of drug loading. Finally, the laryngeal deposition rate of CD-MOF was 57.72 ± 2.19% improved by SCU, about two times higher than that of CD-MOF, when it was determined by Next Generation Impactor (NGI) at 65 L/min. As a proof of concept, pharyngolaryngitis therapeutic agent dexamethasone (DEX) had improved laryngeal deposition after being co-encapsulated with SCU in CD-MOF. The molecular simulation demonstrated the configuration of SCU in CD-MOF and its contribution to the free energy of the SCU@CD-MOF, which defined the enhanced laryngeal anchoring. In conclusion, the glycosides-like SCU could effectively enhance the anchoring of CD-MOF particles to the larynx to facilitate the treatment of laryngeal diseases.

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“…In this experiment, the angle of repose of SCU@CD-MOF was determined by the fixed cone method 45 , 46 , 47 . Two funnels with a diameter of 7.0 cm were taken in series on an iron stand.…”

Section: Methodsmentioning

confidence: 99%

Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery

Zhao

Guo

Wang

et al. 2020

Acta Pharmaceutica Sinica B

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“…No signs of toxicity were expected, since all the samples were obtained by using recognized biocompatible excipients [45]. Moreover, in vivo administration of RIF in rats did not exhibited any evidence of toxicity after inhalation [46]. On the contrary, a mild neutrophilic infiltration in mice treated with SLNas/MS was noticed ( Figure 6) even if MR activation has been generally recognized as a promoter of the anti-inflammatory response [47][48][49].…”

Section: Slnas Biodistribution In the Pulmonary Regionmentioning

confidence: 96%

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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“…Nanomedicines have higher stability and increased circulation time, and improve targeted cargo delivery thereby resulting in enhanced efficacy while limiting drug toxicity (1). Numerous types of nanoparticles, including alginate (2), PLGA (3, 4, 5, 6, 7, 8), silver (9, 10), silver and zinc (11, 12), polymeric (13), gallium (III) (14), chitosan (15, 16), lipid (17), and silica (18) have been reported as drug delivery vehicles for therapeutics that target infectious diseases. For example, acrylate nanoparticles increased the intracellular concentration of anti-tuberculosis chemotherapeutics to macrophages compared to free drugs (19).…”

Section: Introductionmentioning

confidence: 99%

In vitro Pharmacokinetic Cell Culture System that Simulates Physiologic Drug and Nanoparticle Exposure to Macrophages

et al. 2019

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Purpose An in vitro dynamic pharmacokinetic (PK) cell culture system was developed to more precisely simulate physiologic nanoparticle/drug exposure. Methods A dynamic PK cell culture system was developed to more closely reflect physiologic nanoparticle/drug concentrations that are changing with time. Macrophages were cultured in standard static and PK cell culture systems with rifampin (RIF; 5 μg/ml) or β-glucan, chitosan coated, poly(lactic-co-glycolic) acid (GLU-CS-PLGA) nanoparticles (RIF equivalent 5 μg/ml) for 6 h. Intracellular RIF concentrations were measured by UPLC/MS. Antimicrobial activity against M. smegmatis was tested in both PK and static systems. Results The dynamic PK cell culture system mimics a one-compartment elimination pharmacokinetic profile to properly mimic in vivo extracellular exposure. GLU-CS-PLGA nanoparticles increased intracellular RIF concentration by 37% compared to free drug in the dynamic cell culture system. GLU-CS-PLGA nanoparticles decreased M. smegmatis colony forming units compared to free drug in the dynamic cell culture system. Conclusions The PK cell culture system developed herein enables more precise simulation of human PK exposure (i.e., drug dosing and drug elimination curves) based on previously obtained PK parameters.

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Dry-Powder Inhaler Formulation of Rifampicin: An Improved Targeted Delivery System for Alveolar Tuberculosis

Abstract: The carrier-mediated dry-powder inhaler of rifampicin could serve as an improved and efficient system for local targeting of drugs into the lungs.

Cited by 21 publications

References 32 publications

Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery

Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery

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

In vitro Pharmacokinetic Cell Culture System that Simulates Physiologic Drug and Nanoparticle Exposure to Macrophages

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