Nebulized coenzyme Q 10 nanosuspensions: A versatile approach for pulmonary antioxidant therapy

Rossi, Irene; Sonvico, Fabio; McConville, Jason T.; Rossi, Francesca; Frőhlich, Eleonore; Zellnitz, Sarah; Rossi, Alessandra; Favero, Elena Del; Bettini, Ruggero; Buttini, Francesca

doi:10.1016/j.ejps.2017.10.024

Cited by 26 publications

(13 citation statements)

References 51 publications

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“…In fact, scale-up manufacturing issues and poor process control have been indicated as some of the critical underlying problems that hampered the transfer of nanomedicines to the clinic [44]. At the same time, the potential of nanoformulations, such as lipid nanovectors, and their inclusion in oral [45,46] or transmucosal medicinal products have not yet been fully studied [47,48,49].…”

Section: Discussionmentioning

confidence: 99%

“…However, these systems contain a steric stabilizer, i.e., the non-ionic and PEGylated surfactant TPGS, and as a consequence, the absorption of the surfactant on nanoparticle surface decreases the zeta potential, due to the shift of the shear plane of the electrical double layer existing around each particle [10]. However, the surfactant layer provides a steric contribution to particle stability, due to the presence of the hydrophilic PEG polymer chains [47].…”

Section: Discussionmentioning

confidence: 99%

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Ucuùba (Virola surinamensis) Fat-Based Nanostructured Lipid Carriers for Nail Drug Delivery of Ketoconazole: Development and Optimization Using Box-Behnken Design

et al. 2019

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Ucuùba fat is fat obtained from a plant found in South America, mainly in Amazonian Brazil. Due to its biocompatibility and bioactivity, Ucuùba fat was used for the production of ketoconazole-loaded nanostructured lipid carriers (NLC) in view of an application for the treatment of onychomycosis and other persistent fungal infections. The development and optimization of Ucuùba fat-based NLC were performed using a Box-Behnken design of experiments. The independent variables were surfactant concentration (% w/v), liquid lipids concentration (% w/v), solid lipids concentration (% w/v), while the outputs of interest were particle size, polydispersity index (PDI) and drug encapsulation efficiency (EE). Ucuùba fat-based NLC were produced and the process was optimized by the development of a predictive mathematical model. Applying the model, two formulations with pre-determined particle size, i.e., 30 and 85 nm, were produced for further evaluation. The optimized formulations were characterized and showed particle size in agreement to the predicted value, i.e., 33.6 nm and 74.6 nm, respectively. The optimized formulations were also characterized using multiple techniques in order to investigate the solid state of drug and excipients (DSC and XRD), particle morphology (TEM), drug release and interactions between the formulation components (FTIR). Furthermore, particle size, surface charge and drug loading efficiency of the formulations were studied during a one-month stability study and did not show evidence of significant modification.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ucuùba (Virola surinamensis) Fat-Based Nanostructured Lipid Carriers for Nail Drug Delivery of Ketoconazole: Development and Optimization Using Box-Behnken Design

et al. 2019

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“…Vitamin E is considered the main antioxidant in biological membranes (32), and many of its beneficial effects in immunoregulation (33) are attributed to its radical scavenging activity in lipophilic environments, resulting in the stabilization of polyunsaturated fatty acids in membrane lipids. At the same time, the physical properties of vitamin E make this molecule and its derivatives useful carriers for drug delivery in general (16) and for pulmonary drug delivery in particular (34–36). Given our results, it might be feasible to consider including vitamin E in antibiotic formulations delivered by nebulization to patients with cystic fibrosis to increase their efficacy.…”

Section: Discussionmentioning

confidence: 99%

Vitamin E Increases Antimicrobial Sensitivity by Inhibiting Bacterial Lipocalin Antibiotic Binding

Naguib

Valvano

2018

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Bacteria exposed to stress mediated by sublethal antibiotic concentrations respond by adaptive mechanisms leading to an overall increase of antibiotic resistance. One of these mechanisms involves the release of bacterial proteins called lipocalins, which have the ability to sequester antibiotics in the extracellular space before they reach bacterial cells. We speculated that interfering with lipocalin-mediated antibiotic binding could enhance the efficacy of antibiotics to kill bacteria. In this work, we report that when combined with bactericidal antibiotics, vitamin E contributes to enhance bacterial killing both in vitro and in vivo. This adjuvant effect of vitamin E requires the presence of BcnA, a bacterial lipocalin produced by the cystic fibrosis pathogen Burkholderia cenocepacia. Since most bacteria produce lipocalins like BcnA, we propose that our findings could be translated into making novel antibiotic adjuvants to potentiate bacterial killing by existing antibiotics.

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“…Antioxidant coenzyme Q10 nanosuspension stabilized with PEG32 stearate demonstrated maximum respirable fraction (70.6%) having smallest mass median aerodynamic diameter (3.02 μm) in comparison to nanosuspension stabilized with lecithin and Vitamin E TPGS. In vitro cellular toxicity carried out utilizing A549 human lung cells showed no noticeable cytotoxicity for the nanosuspension [72]. Due to the unique physicochemical characteristics, uniform and narrow size distribution of the nanoparticles, it is unlikely to cause uneven drug distribution and drug delivery in lung, when compared to microparticulate inhalation aerosols.…”

Section: Pulmonary Drug Deliverymentioning

confidence: 98%

Emerging role of nanosuspensions in drug delivery systems

2020

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Rapid advancement in drug discovery process is leading to a number of potential new drug candidates having excellent drug efficacy but limited aqueous solubility. By virtue of the submicron particle size and distinct physicochemical properties, nanosuspension has the potential ability to tackle many formulation and drug delivery issues typically associated with poorly water and lipid soluble drugs. Conventional size reduction equipment such as media mill and high-pressure homogenizers and formulation approaches such as precipitation, emulsion-solvent evaporation, solvent diffusion and microemulsion techniques can be successfully implemented to prepare and scale-up nanosuspensions. Maintaining the stability in solution as well as in solid state, resuspendability without aggregation are the key factors to be considered for the successful production and scale-up of nanosuspensions. Due to the considerable enhancement of bioavailability, adaptability for surface modification and mucoadhesion for drug targeting have significantly expanded the scope of this novel formulation strategy. The application of nanosuspensions in different drug delivery systems such as oral, ocular, brain, topical, buccal, nasal and transdermal routes are currently undergoing extensive research. Oral drug delivery of nanosuspension with receptor mediated endocytosis has the promising ability to resolve most permeability limited absorption and hepatic first-pass metabolism related issues adversely affecting bioavailability. Advancement of enabling technologies such as nanosuspension can solve many formulation challenges currently faced among protein and peptide-based pharmaceuticals.

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Nebulized coenzyme Q 10 nanosuspensions: A versatile approach for pulmonary antioxidant therapy

Cited by 26 publications

References 51 publications

Ucuùba (Virola surinamensis) Fat-Based Nanostructured Lipid Carriers for Nail Drug Delivery of Ketoconazole: Development and Optimization Using Box-Behnken Design

Ucuùba (Virola surinamensis) Fat-Based Nanostructured Lipid Carriers for Nail Drug Delivery of Ketoconazole: Development and Optimization Using Box-Behnken Design

Vitamin E Increases Antimicrobial Sensitivity by Inhibiting Bacterial Lipocalin Antibiotic Binding

Emerging role of nanosuspensions in drug delivery systems

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