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• W2079396811 endingPage "4933" @default.
• W2079396811 startingPage "4915" @default.
• W2079396811 abstract "Aqueous colloidal dispersions of amorphous cyclosporin A (CsA) nanoparticles, intended for pulmonary delivery, were formed by antisolvent precipitation and stabilized with 10% polysorbate 80. Dissolution of the dispersion of CsA nanoparticles produced supersaturation values 18 times the aqueous equilibrium solubility. Nebulization of the dispersion to mice produced therapeutic lung levels and systemic concentrations below toxic limits. The sizes of the aerosolized aqueous droplets are optimal for deep lung deposition, whereas the amorphous drug nanoparticles facilitate rapid dissolution. A dissolution/permeation model was developed to characterize the effects of particle size, solubility, and drug dose on the absorption half-lives of poorly water soluble drugs in the alveolar epithelium. For crystalline 3 µm particles with a solubility of 1 µg/mL, the half-life for absorption was estimated to be 500 min. The half-life may be reduced to less than 1 min by increasing the solubility by a factor of 100 with an amorphous form as well as by decreasing the particle size 10-fold. The in vitro and in vivo data, as well as the dissolution/permeation model, indicate that nebulization of amorphous nanoparticle suspensions has the potential to enhance lung epithelial absorption markedly for poorly water soluble drugs, relative to respiratory delivery of crystalline, micron-sized particles." @default.
• W2079396811 created "2016-06-24" @default.
• W2079396811 creator A5014751583 @default.
• W2079396811 creator A5045532207 @default.
• W2079396811 creator A5055542138 @default.
• W2079396811 creator A5080881086 @default.
• W2079396811 date "2008-11-01" @default.
• W2079396811 modified "2023-10-17" @default.
• W2079396811 title "Amorphous cyclosporin nanodispersions for enhanced pulmonary deposition and dissolution" @default.
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• W2079396811 doi "https://doi.org/10.1002/jps.21367" @default.
• W2079396811 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18351641" @default.
• W2079396811 hasPublicationYear "2008" @default.

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