RESUMO
A series of O-substituted alkylglyceryl chitosans with systematically varied alkyl chain length and degree of grafting has been employed for the formulation of aqueous nanoparticulate systems, which were in turn investigated for their effects on a modeled blood-brain-barrier system of mouse-brain endothelial cells. Barrier function measurements employing electric cell-substrate impedance sensing and analyses of tight junction-specific protein profiles have indicated that the alkylglyceryl-modified chitosan nanoparticles impact upon the integrity of the model blood-brain barrier, whereas confocal microscopy experiments have demonstrated the efficient cellular uptake and the perinuclear localization of these nanoparticles. The application of nanoparticles to the model blood-brain barrier effected an increase in its permeability, as demonstrated by following the transport of the tracer molecule fluorescein isothiocyanate.
Assuntos
Barreira Hematoencefálica/metabolismo , Quitosana/metabolismo , Sistemas de Liberação de Medicamentos , Células Endoteliais/metabolismo , Nanopartículas/química , Animais , Barreira Hematoencefálica/química , Encéfalo/irrigação sanguínea , Encéfalo/citologia , Sobrevivência Celular , Células Cultivadas , Quitosana/química , Células Endoteliais/química , Fluoresceína-5-Isotiocianato/química , Fluoresceína-5-Isotiocianato/metabolismo , Camundongos , Modelos Animais , Tamanho da Partícula , Permeabilidade , Propriedades de SuperfícieRESUMO
A series of O-substituted alkylglyceryl chitosans with systematically varied degrees of grafting was prepared through synthetic steps that involved the protection of amino moieties via phthaloylation and employed for the formulation of aqueous nanoparticulate systems that may be capable of delivering drugs to the brain. Dynamic light scattering studies have shown that nanoparticles with physiologically relevant aqueous stabilities may be prepared following the partial quaternization of these alkylglyceryl-modified chitosans. Preliminary in vitro tests using a mouse-brain endothelial cell model have indicated the efficient cellular uptake of these nanoparticles and identified butylglyceryl chitosan and butylglyceryl N,N,N-trimethyl chitosan as promising materials for the formulation of colloidal systems that could act as drug carriers into the brain.