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
In this study, three different molecules (cholesterol, phosphatidic acid, and polyethylene glycol) were used for the stabilization of liposomes during the nebulization process. The purpose of this article is to answer the question of whether the change in the composition of liposomes affected the parameters of generated aerosol and whether the nebulization process affected observed properties of liposomes. Firstly, liposomes with different composition were prepared and their properties were checked by dynamic and electrophoretic light scattering. The membrane properties were measured by fluorescence spectroscopy - especially generalized polarization (Laurdan) and anisotropy (Diphenylhexatriene). The same characteristic of liposomes was measured after the nebulization by vibrating mesh nebulizer. Cholesterol was capable of liposome stabilization because of increased membrane fluidity. The membrane properties of the outer and inner parts were not influenced by the nebulization process. Electrostatic stabilization was successful for the lowest concentration of phosphatidic acid, but after the nebulization process the hydration of the membrane outer part was changed. Higher amount of PEG needs to be added for successful steric stabilization. The nebulization process of the two lowest concentrations of PEG slightly influenced immobilized water and the rigidity of inner part of the membrane (especially around the phase transition temperature).
- MeSH
- aerosoly MeSH
- chirurgické síťky * MeSH
- liposomy * MeSH
- nebulizátory a vaporizátory MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
Controlled pulmonary drug delivery systems employing non-spherical particles as drug carriers attract considerable attention nowadays. Such anisotropic morphologies may travel deeper into the lung airways, thus enabling the efficient accumulation of therapeutic compounds at the point of interest and subsequently their sustained release. This study focuses on the fabrication of electrospun superparamagnetic polymer-based biodegradable microrods consisting of poly(l-lactide) (PLLA), polyethylene oxide (PEO) and oleic acid-coated magnetite nanoparticles (OA·Fe3O4). The production of magnetite-free (0% wt. OA·Fe3O4) and magnetite-loaded (50% and 70% wt. Fe3O4) microrods was realized upon subjecting the as-prepared electrospun fibers to UV irradiation, followed by sonication. Moreover, drug-loaded microrods were fabricated incorporating methyl 4-hydroxybenzoate (MHB) as a model pharmaceutical compound and the drug release profile from both, the drug-loaded membranes and the corresponding microrods was investigated in aqueous media. In addition, the magnetic properties of the produced materials were exploited for remote induction of hyperthermia under AC magnetic field, while the possibility to reduce transport losses and enhance the targeted delivery to lower airways by manipulation of the airborne microrods by DC magnetic field was also demonstrated.
