A Comprehensive Physicochemical, In Vitro and Molecular Characterization of Letrozole Incorporated Chitosan-Lipid Nanocomplex
Jazyk angličtina Země Spojené státy americké Médium electronic
Typ dokumentu časopisecké články
PubMed
30850895
DOI
10.1007/s11095-019-2597-4
PII: 10.1007/s11095-019-2597-4
Knihovny.cz E-zdroje
- Klíčová slova
- PLN, aromatase inhibitor, non-everted sac study, chitosan-lipid nanocomplex, letrozole, molecular dynamics,
- MeSH
- buňky PC12 MeSH
- chitosan chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- krysa rodu Rattus MeSH
- lékové transportní systémy metody MeSH
- letrozol chemie MeSH
- lidé MeSH
- lipidy chemie MeSH
- MFC-7 buňky MeSH
- nádorové buněčné linie MeSH
- nanočástice chemie MeSH
- nosiče léků chemie MeSH
- polymery chemie MeSH
- simulace molekulární dynamiky MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chitosan MeSH
- letrozol MeSH
- lipidy MeSH
- nosiče léků MeSH
- polymery MeSH
PURPOSE: The aim of this study is to show a new mesomicroscopic insight into Letrozole (LTZ) loaded nanocomplexes and their ex vivo characteristics as a drug delivery system. METHODS: The LTZ loaded hybrid chitosan-based carrier was fabricated using a modified ionic crosslinking technique and characterized in more detail. To understand the mechanism of LTZ action encapsulated in the hybrid polymer-lipid carrier, all-atom molecular dynamics simulations were also used. RESULTS: The physicochemical properties of the carrier demonstrated the uniform morphology, but different drug loading ratios. In vitro cytotoxic activity of the optimized carrier demonstrated IC50 of 67.85 ± 0.55 nM against breast cancer cell line. The ex vivo study showed the positive effect of nanocomplex on LTZ permeability 7-10 fold greater than the free drug. The molecular dynamic study also confirmed the prsence of hydrophobic peak of lipids at a distance of 5 Å from the center of mass of LTZ which proved drug entrapment in the core of nanocomplex. CONCLUSIONS: The hybrid nanoparticle increased the cytotoxicity and tissue permeability of LTZ for oral delivery. This study also confirmed the atomic mesostructures and interaction of LTZ in the core of hybrid polymer-lipid nanoparticles.
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