Inhalable dry-emulsion formulation of cyclosporine A with improved anti-inflammatory effects in experimental asthma/COPD-model rats

Onoue, Satomi; Sato, Hideyuki; Ogawa, Kumiko; Kojo, Yoshiki; Aoki, Yosuke; Kawabata, Youhei; Wada, Koichi; Mizumoto, Takao; Yamada, Shizuo

doi:10.1016/j.ejpb.2011.10.003

Cited by 43 publications

(19 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From day 14, the animals were challenged with aerosolized OVA (2% in N.S.) for 20 min a day over one week (8,9), and 30 min prior to the last OVA challenge (-)SPFF, (±)SPFF and (+)SPFF at 0.1, 0.25 and 0.5 mg/kg dissolved in 0.7% sodium carboxymethyl cellulose (CMC-Na) was administered intragastrically (i.g. ), respectively, to rats in the drug-treated groups.…”

Section: Determination Of Cyclic Adenosine Monophosphate (Camp) Levelmentioning

confidence: 99%

Stereoselective activity of 2-(4-amino-3-chloro-5- trifluomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride to improve the pulmonary function in asthma

Pan

et al. 2014

Biomedical Reports

View full text Add to dashboard Cite

Abstract. Asthma is a chronic airway disease that is characterized by significantly exacerbated bronchospasms and marked inflammation of the airways. Although the etiology of asthma remains to be determined, genetic predisposition is one of the factors involved. β 2 -agonists compounds may serve as options for the treatment of bronchial asthma. The aim of the present study was to investigate the effects of 2-(4-amino-3-chloro-5-t rifluomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride (SPFF) and its enantiomers with regard to improving asthmatic pulmonary function and selective binding to β 2 -adrenergic receptor. The bronchoconstrictor action of histamine in guinea pigs was conducted and the results demonstrated that (-)SPFF and (±)SPFF could significantly inhibit the increase of bronchoconstriction induced by histamine, while (+)SPFF did not show an effect. Inflammatory mediator release from allergic lung tissues was determined and it was found that (±)SPFF showed the highest activity among all the tested compounds, while the efficacy of (-)SPFF was similar to that of (+)SPFF. SPFF and its enantiomers stimulated cyclic adenosine monophosphate (cAMP) production in the asthmatic lung tissues examined, showing that asthmatic lung tissues had a significant cAMP enhancement in response to (-)SPFF and (±)SPFF compared with (+)SPFF. Cardiac contractility of the right atria was assessed in the guinea pigs to establish the receptor selectivity of the compounds. The results indicated that all the compounds had high affinities to the β 2 receptor. In conclusion, with regards to asthmatic pulmonary function improvement, (-)SPFF was more efficient as compared to (+) SPFF, while no significant difference was observed for the receptor selectivity of (-)SPFF and (+)SPFF.

show abstract

Section: Determination Of Cyclic Adenosine Monophosphate (Camp) Levelmentioning

confidence: 99%

Stereoselective activity of 2-(4-amino-3-chloro-5- trifluomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride to improve the pulmonary function in asthma

Pan

et al. 2014

Biomedical Reports

View full text Add to dashboard Cite

show abstract

“…16 In addition to the oral dosage form, an inhalable dry emulsion of cyclosporin A was proposed for the treatment of asthma, chronic obstructive pulmonary disease (COPD), and allograft rejection after pulmonary transplantation, and the insufflated dry emulsions showed higher potency than did cyclosporin A particles, in a rat model of acute airway inflammation. 19 …”

mentioning

confidence: 99%

“…In general, drug delivery systems employing nanotechnologies are designed to be administered via injection, transdermally, or orally, although recent studies have demonstrated the promising outcomes with pulmonary administration of nanodrug systems. 19,20 Inhaled particles undergo pulmonary clearance, such as mucociliary clearance and macrophage clearance, leading to a limited duration of action. However, nanoparticles have been praised for their advantageous drug delivery properties to the lung, including their avoidance of mucociliary and macrophage clearance and long residence times before degradation or translocation by epithelial cells takes place.…”

mentioning

confidence: 99%

Nanodrugs: pharmacokinetics and safety

Onoue¹,

Yamada²,

Chan³

2014

IJN

Self Cite

303

153

View full text Add to dashboard Cite

To date, various nanodrug systems have been developed for different routes of administration, which include dendrimers, nanocrystals, emulsions, liposomes, solid lipid nanoparticles, micelles, and polymeric nanoparticles. Nanodrug systems have been employed to improve the efficacy, safety, physicochemical properties, and pharmacokinetic/pharmacodynamic profile of pharmaceutical substances. In particular, functionalized nanodrug systems can offer enhanced bioavailability of orally taken drugs, prolonged half-life of injected drugs (by reducing immunogenicity), and targeted delivery to specific tissues. Thus, nanodrug systems might lower the frequency of administration while providing maximized pharmacological effects and minimized systemic side effects, possibly leading to better therapeutic compliance and clinical outcomes. In spite of these attractive pharmacokinetic advantages, recent attention has been drawn to the toxic potential of nanodrugs since they often exhibit in vitro and in vivo cytotoxicity, oxidative stress, inflammation, and genotoxicity. A better understanding of the pharmacokinetic and safety characteristics of nanodrugs and the limitations of each delivery option is necessary for the further development of efficacious nanodrugs with high therapeutic potential and a wide safety margin. This review highlights the recent progress in nanodrug system development, with a focus on the pharmacokinetic advantages and safety challenges.

show abstract

“…DPIs are portable and more effective than nebulizers which require routine maintenance (Thai et al, 2010). Organic solvents and other solubilizers are usually added in nebulizers and aerosols (Klyashchitsky and Owen, 1999), easily leading to local irritant potency (Onoue et al, 2012). Moreover, dry powders can improve drug stability during storage due to low chemical degradation in the solid state (Adi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Dimethyl silicone dry nanoemulsion inhalations: Formulation study and anti-acute lung injury effect

Zhu

Dong

et al. 2015

International Journal of Pharmaceutics

View full text Add to dashboard Cite

Inhalable dry-emulsion formulation of cyclosporine A with improved anti-inflammatory effects in experimental asthma/COPD-model rats

Cited by 43 publications

References 22 publications

Stereoselective activity of 2-(4-amino-3-chloro-5- trifluomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride to improve the pulmonary function in asthma

Stereoselective activity of 2-(4-amino-3-chloro-5- trifluomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride to improve the pulmonary function in asthma

Nanodrugs: pharmacokinetics and safety

Dimethyl silicone dry nanoemulsion inhalations: Formulation study and anti-acute lung injury effect

Contact Info

Product

Resources

About