Pharmacokinetic/pulmokinetic analysis of optimized lung targeted spray dried ketotifen-dextran core shell nanocomplexes-in-microparticles.
Int J Biol Macromol
; 139: 678-687, 2019 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-31381926
ABSTRACT
A passive lung targeted system for controlled lung delivery of ketotifen (KT) was developed based on the green complexation of dextran sulphate (DS) and KT. Achieving deep lung deposition of high drug fraction, while evading lung defense mechanisms were set as goals. Optimized uniform negatively charged nanocomplexes (NC), <80â¯nm, were obtained at KT/DS weight ratio of 10.66 to 10.5 and 1% surfactant concentration with 90% drug complexation efficiency. The interaction between KT and DS and matrix formation were evidenced by Fourier-transform infrared (FT-IR) spectra and differential scanning calorimetry (DSC) studies. A respirable particle percent reaching 67.41⯱â¯2.6% was obtained following co-spray drying NC containing poloxamer with leucine. A higher lung/plasma partitioning was obtained following pulmonary administration of selected nanocomplexes in microparticles (NCEMP) to rats compared to oral and intravenous (iv) routes. A new core shell nanocomplex formed of DS and KT as main substrates exhibited a potential for lung targeting of the anti-asthmatic drug.
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Base de dados:
MEDLINE
Assunto principal:
Dextranos
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Sistemas de Liberação de Medicamentos
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Nanopartículas
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Cetotifeno
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Pulmão
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article