Development of extra-fine particles containing nanosized meloxicam for deep pulmonary delivery: In vitro aerodynamic and cell line measurements

Party, Petra; Kókai, Dávid; Burián, Katalin; Nagy, Attila; Hopp, B.; Ambrus, Rita

doi:10.1016/j.ejps.2022.106247

Cited by 18 publications

(8 citation statements)

References 59 publications

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“…At a concentration of 50 µg/mL, samples recorded a % cell viability between 63 and 83%, while at a concentration of 5 µg/mL, a high % cell viability was found (85–125%) with U937. These results aligned with previously published studies [ 69 ]. Nevertheless, our formulations exhibited very low cytotoxicity towards both cell lines, with live cell percentages between 85 and 125% at 5 µg/mL, which is the concentration used for the anti-inflammatory effect ( Section 2.15 ).…”

Section: Resultssupporting

confidence: 94%

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

Banat,

Csóka,

Paróczai

et al. 2024

Pharmaceuticals

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Pulmonary inflammations such as chronic obstructive pulmonary disease and cystic fibrosis are widespread and can be fatal, especially when they are characterized by abnormal mucus accumulation. Inhaled corticosteroids are commonly used for lung inflammations despite their considerable side effects. By utilizing particle engineering techniques, a combined dry powder inhaler (DPI) comprising nanosized ketoprofen-embedded mannitol-coated microparticles was developed. A nanoembedded microparticle system means a novel advance in pulmonary delivery by enhancing local pulmonary deposition while avoiding clearance mechanisms. Ketoprofen, a poorly water-soluble anti-inflammatory drug, was dispersed in the stabilizer solution and then homogenized by ultraturrax. Following this, a ketoprofen-containing nanosuspension was produced by wet-media milling. Furthermore, co-spray drying was conducted with L-leucine (dispersity enhancer) and mannitol (coating and mucuactive agent). Particle size, morphology, dissolution, permeation, viscosity, in vitro and in silico deposition, cytotoxicity, and anti-inflammatory effect were investigated. The particle size of the ketoprofen-containing nanosuspension was ~230 nm. SEM images of the spray-dried powder displayed wrinkled, coated, and nearly spherical particles with a final size of ~2 µm (nano-in-micro), which is optimal for pulmonary delivery. The mannitol-containing samples decreased the viscosity of 10% mucin solution. The results of the mass median aerodynamic diameter (2.4–4.5 µm), fine particle fraction (56–71%), permeation (five-fold enhancement), and dissolution (80% release in 5 min) confirmed that the system is ideal for local inhalation. All samples showed a significant anti-inflammatory effect and decreased IL-6 on the LPS-treated U937 cell line with low cytotoxicity. Hence, developing an innovative combined DPI comprising ketoprofen and mannitol by employing a nano-in-micro approach is a potential treatment for lung inflammations.

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Section: Resultssupporting

confidence: 94%

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

Banat,

Csóka,

Paróczai

et al. 2024

Pharmaceuticals

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“…Results of the pre or post-deformation neutron tomography of a Bentheim sandstone sample at ex-situ at the loading of 40 MPa. This shows that the internal structure can be obtained for 3D-DIC and the 3D strain field [7]. An investigation of the Extra-fine dry powder inhalers to reach the smaller airway.…”

Section: Introductionmentioning

confidence: 80%

Finite Element Method of the Influence Evaluation of the Percentage of Fine Particles of Marine Clay at the Different Depth Variations to the Total Volumetric Strain of the Soft Clay Ground

2023

EESRR

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Finite element method of the influence evaluation of the percentage of fine particles of marine clay at the different depth variations to the total volumetric strain of the soft clay ground is determined by the Viet Nam standard TCVN 4196:2012; TCVN 4102:2012; TCVN 4197:2012; TCVN 4199:2012. Results show clearly the percentage of the fine clay particle and the total volumetric strain (ε) with depths. The minimum value of 12% and 0.00002617 at 19.3m depth; whereas the maximum value of 38% and 0.00002609 at 25.3m depth. Moreover, a consideration of the relationship between Internal friction angle, Cohesive force, Water content, Saturation, Porosity, Viscosity, and Plasticity index with depths. Results show remarkably the increasing of the depths as the variations of the percentage of fine particles of marine clay and cohesive force, viscosity, water content, and porosity; compared with the decrease of the plasticity and internal friction angle. It is easy to conclude that the total volumetric strain of the soft clay ground is a stable and safe state to use and design the building, construction, and reference of engineers, geologists, scientists, and so on in the future.

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“…Raw CsA exhibited an endothermic peak at 132.6 °C related to the glass transition temperature [ 53 ], followed by a broad endothermic peak at 260.2 °C for melting of partial crystalline form and decomposition at higher temperatures. LEU exhibited a sharp endothermic peak at 307.5 °C related to the melting point, reflecting its highly crystalline structure [ 54 ]. HPMC exhibited a broad endothermic peak at 82.1 °C related to the water loss event, with no melting peak when heating up to 320 °C, reflecting its amorphous nature [ 55 ].…”

Section: Resultsmentioning

confidence: 99%

Development of Large Hollow Particles for Pulmonary Delivery of Cyclosporine A

Huang,

Tang,

Meng

et al. 2023

Pharmaceutics

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The purpose of this study was to prepare large hollow particles (LHPs) by spray drying for pulmonary delivery of cyclosporine A (CsA), using L-Leucine (LEU) and hydroxypropyl methylcellulose (HPMC) as excipients and ammonium bicarbonate (AB) as a porogen. The prepared LHPs were spherical particles composed of both CsA and LEU on the surface and HPMC on the inner layer. The formulation of CsA-LEU-0.8HPMC-AB as typical LHPs showed excellent in vitro aerodynamic performance with a minimum mass median aerodynamic diameter (MMAD) of 1.15 μm. The solubility of CsA-LEU-0.8HPMC-AB was about 5.5-fold higher than that of raw CsA, and the dissolution of CsA-LEU-0.8HPMC-AB suggested that the drug was released within 1 h. The cell viability of the A549 cell line showed that CsA-LEU-0.8HPMC-AB was safe for delivering CsA to the lungs. In addition, inhalation administration of CsA-LEU-0.8HPMC-AB with the Cmax and AUC0–∞ increasing by about 2-fold and 2.8-fold compared with the oral administration of Neoral® could achieve therapeutic drug concentrations with lower systemic exposure and significantly improve the in vivo bioavailability of CsA. From these findings, the LHPs, with the advantage of avoiding alveolar macrophage clearance, could be a viable choice for delivering CsA by inhalation administration relative to oral administration.

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Development of extra-fine particles containing nanosized meloxicam for deep pulmonary delivery: In vitro aerodynamic and cell line measurements

Cited by 18 publications

References 59 publications

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

Finite Element Method of the Influence Evaluation of the Percentage of Fine Particles of Marine Clay at the Different Depth Variations to the Total Volumetric Strain of the Soft Clay Ground

Development of Large Hollow Particles for Pulmonary Delivery of Cyclosporine A

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