This contribution is focused on the preparation of a liposomal drug delivery system of erlotinib resisting the nebulization process that could be used for local treatment of non-small-cell lung cancer. Liposomes with different compositions were formulated to reveal their influence on the encapsulation efficiency of erlotinib. An encapsulation efficiency higher than 98 % was achieved for all vesicles containing phosphatidic acid (d ≈ 100 nm, ζ = - 43 mV) even in the presence of polyethylene glycol (d ≈ 150 nm, ζ = - 17 mV) which decreased this value in all other formulas. The three most promising formulations were nebulized by two air-jet and two vibrating mesh nebulizers, and the aerosol deposition in lungs was calculated by tools of computational fluid and particle mechanics. According to the numerical simulations and measurements of liposomal stability, air-jet nebulizers generated larger portion of the aerosol able to penetrate deeper into the lungs, but the delivery is likely to be more efficient when the formulation is administered by Aerogen Solo vibrating mesh nebulizer because of a higher portion of intact vesicles after the nebulization. The leakage of encapsulated drug from liposomes nebulized by this nebulizer was lower than 2 % for all chosen vesicles.
- MeSH
- aplikace inhalační MeSH
- bronchodilatancia MeSH
- erlotinib MeSH
- lidé MeSH
- liposomy MeSH
- nádory plic * MeSH
- nebulizátory a vaporizátory MeSH
- nemalobuněčný karcinom plic * MeSH
- plíce MeSH
- respirační aerosoly a kapénky MeSH
- systémy cílené aplikace léků MeSH
- velikost částic MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The degree of response to subthalamic nucleus deep brain stimulation (STN-DBS) is individual and hardly predictable. We hypothesized that DBS-related changes in cortical network organization are related to the clinical effect. Network analysis based on graph theory was used to evaluate the high-density electroencephalography (HDEEG) recorded during a visual three-stimuli paradigm in 32 Parkinson's disease (PD) patients treated by STN-DBS in stimulation "off" and "on" states. Preprocessed scalp data were reconstructed into the source space and correlated to the behavioral parameters. In the majority of patients (n = 26), STN-DBS did not lead to changes in global network organization in large-scale brain networks. In a subgroup of suboptimal responders (n = 6), identified according to reaction times (RT) and clinical parameters (lower Unified Parkinson's Disease Rating Scale [UPDRS] score improvement after DBS and worse performance in memory tests), decreased global connectivity in the 1-8 Hz frequency range and regional node strength in frontal areas were detected. The important role of the supplementary motor area for the optimal DBS response was demonstrated by the increased node strength and eigenvector centrality in good responders. This response was missing in the suboptimal responders. Cortical topologic architecture is modified by the response to STN-DBS leading to a dysfunction of the large-scale networks in suboptimal responders.
- MeSH
- elektroencefalografie MeSH
- hluboká mozková stimulace * MeSH
- hodnocení výsledků zdravotní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozková kůra patofyziologie MeSH
- nervová síť patofyziologie MeSH
- nucleus subthalamicus patofyziologie MeSH
- Parkinsonova nemoc patofyziologie terapie MeSH
- psychomotorický výkon fyziologie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
