Viscosity effects on nebulisation of aqueous solutions

Callion, O.N.M. Mc; Patel, Manan

doi:10.1016/0378-5173(95)04291-1

Cited by 51 publications

(32 citation statements)

References 4 publications

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“…The primary factors influencing aerosol particle size and, ultimately, the site of aerosol deposition include the design of the inhalation device, as well as the physico-chemical properties of the formulation [9]. Both the viscosity of the solution and surface tension characteristics play an important part in the formation of the droplets during nebuliza-tion [10,11]. To date, there are no data available regarding the characterization of aerosols obtained with such cyclodextrins solutions.…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrins as a potential carrier in drug nebulization

Évrard

Bertholet

Guéders

et al. 2004

Journal of Controlled Release

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The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs.We have studied the feasibility of using different cyclodextrins (CDs) to elaborate pharmaceutical formulations for the inhalation route and tested the short-term toxicity of such formulations administered by inhalation to C57BL/6 mice.We have shown that HP-β-CD, γ-CD, as well as RAMEB aqueous solutions can undergo aerosolization and that the resulting droplet-size ranges are compatible with pulmonary deposition. In vivo, we have demonstrated that short-term exposure to inhaled HP-β-CD, γ-CD and RAMEB solutions are non-toxic after assessing bronchoalveolar lavage (BAL), lung and kidney histology, bronchial responsiveness to methacholine and blood urea. The only change noted is a slight increase in lymphocyte count in the BAL after HP-β-CD and γ-CD inhalation.We conclude that CDs are useful in significantly enhancing the solubility of apolar drugs with a view to inhalation therapy although an increase in lymphocyte counts in the BAL after CDs inhalations needs further investigations.

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Section: Introductionmentioning

confidence: 99%

Cyclodextrins as a potential carrier in drug nebulization

Évrard

Bertholet

Guéders

et al. 2004

Journal of Controlled Release

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“…8) Formulations for efficient nebulization are usually designed using empirical methods that consider pharmacological effects and physicochemical properties, including viscosity, surface tension, and drug concentrations. [9][10][11][12][13][14] However, N-siRNA delivery by aerosol inhalation may result in marked losses in transfection efficiency because of the nebulization process. Higher concentrations of N-siRNA are necessary for the therapeutic application of aerosol inhalation techniques than for siRNA carrier systems, including cationic lipids and polymers.…”

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confidence: 99%

Inhalation Properties and Stability of Nebulized Naked siRNA Solution for Pulmonary Therapy

2016

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The use of naked unmodified small interfering RNA (N-siRNA) without vector has previously been investigated as a pulmonary therapy. However, little is known regarding stabilities and aerodynamic particle sizes of N-siRNA-containing droplets; nebulizers have not yet been optimized for N-siRNA solutions. Thus, in this study, we investigated the feasibility of inhaled N-siRNA solutions for pulmonary therapy using nebulization. Various nebulizers and N-siRNA concentrations were assessed in terms of siRNA integrity after nebulization, and inhalation properties including aerodynamic particle size were examined. In comparison with ultrasonic-, air-jet-, and vibrating-mesh nebulizers, N-siRNA integrity was not affected by nebulization. Thus, in further experiments, performances of N-siRNA aerosols with different nebulizers and N-siRNA concentrations were evaluated and screened using an aerodynamic particle sizer (APS) which employed the time-of-flight principle or a cascade impactor. Mean mass aerodynamic diameters of N-siRNA-containing droplets from vibrating-mesh nebulizers tended to decrease with increasing N-siRNA concentrations, reflecting the influence of N-siRNA solutions on surface tension, as indicated by contact angles. These data indicate the utility of APS instruments for investigating the nebulized characteristics of expensive drugs including siRNAs and may facilitate the development of N-siRNA inhalation formulations.Key words small interfering RNA (siRNA); vibrating-mesh nebulizer; aerodynamic particle size; surface tension; contact angle Small interfering RNA (siRNA) has a great therapeutic potential as a tool for the post-transcriptional silencing of target gene expression. 1) Recently, the field of siRNA delivery has rapidly progressed, and the local pulmonary delivery of siRNA has been investigated for various lung diseases. 2,3)Inhalation is the most popular noninvasive method for delivering therapeutic siRNA agents to the lungs 4); local siRNA inhalation therapy reduced virus titers in the lung and attenuated local pulmonary chemokine production after acute lung injury and infection.5,6) However, naked (unmodified) siRNA (N-siRNA) is susceptible to nuclease degradation; siRNA delivery systems facilitating gene silencing efficiency, including those using cationic materials, can have cytotoxic effects. N-siRNA has been delivered with some success to the lung, although systemic delivery of N-siRNA generally fails to produce significant gene silencing effects.3,7) N-siRNA lacks delivery vectors that produce toxicity and inflammation; thus, N-siRNA formulation for pulmonary delivery offers advantages for safety and simplicity. However, few developments of N-siRNA formulations have been reported. Direct pulmonary N-siRNA delivery has been achieved in humans following the inhalation of aerosols generated by inhalers or nebulizers. Three types of inhalation devices are currently available for pulmonary drug delivery, including metered dose inhalers, dry powder inhalers, and nebulizers. Liquid nebulization e...

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“…The mechanism of an action of this type of a device consists in use of compressed air energy to form drops during the drug solutions or suspensions atomization. The construction of inhaler significantly affects the atomization process (McCallion and Patel, 1996;McCallion et al, 1996b;Moskal and Sosnowski, 2009).…”

Section: Introductionmentioning

confidence: 98%