RESUMO
Lactose-derived catanionic vesicles offer unique opportunities to overcome cellular barriers. These potential nanovectors, very easy to formulate as drug delivery systems, are able to encapsulate drugs of various hydrophilicity. This article highlights versatile interaction mechanisms between these catanionic vesicles, labeled with hydrophilic and amphiphilic fluorescent probes, and a mammalian cell line, Chinese Hamster Ovary. Confocal microscopy and flow cytometry techniques show that these vesicles are internalized by cells through cellular energy dependent processes, as endocytosis, but are simultaneously able to spontaneously fuse with cell plasma membranes and release their hydrophilic content directly inside the cytosol. Such innovative and polyvalent nanovectors, able to deliver their content via different internalization pathways, would positively be a great progress for the coadministration of drugs of complementary efficiency.
Assuntos
Endocitose , Fusão de Membrana , Membranas Artificiais , Animais , Células CHO , Cátions , Linhagem Celular , Membrana Celular/metabolismo , Separação Celular , Cricetulus , Citosol , Sistemas de Liberação de Medicamentos , Citometria de Fluxo , Corantes Fluorescentes/química , Glicolipídeos/química , Cinética , Lactose/química , Microscopia Confocal , TensoativosRESUMO
Spontaneous receptor-free membrane fusion with pure lipid systems, used as a cell membrane model, is demonstrated with easy-to-handle lactose-derived catanionic vesicles. This fusion, mediated and controlled by phospholipids, emphasizes the great value of these nanovesicles for enhanced direct cytosolic drug delivery without the shortcomings linked with endocytic pathways.
Assuntos
Membrana Celular/química , Fusão de Membrana , Modelos Biológicos , Nanoestruturas/química , Lipossomas Unilamelares/química , Cátions , Estrutura Molecular , Tensoativos/química , Água/químicaRESUMO
Among drug delivery systems, catanionic vesicles now appear as powerful candidates for pharmaceutical applications because they are relatively cheap and easy to use, thus well corresponding to industrial requirements. Using labelled vesicles made of a tricatenar catanionic surfactant, the work reported here aims at exploring the mechanisms by which internalisation into a cell occurs. The study was performed on various cell types such as phagocytic as well as non-phagocytic cells using confocal laser scanning microscopy and flow cytometry. Using various inhibitors, endocytosis and also a passive process, as probably fusion, were highlighted as interaction phenomena between catanionic vesicles and cell membranes. Finally, the interaction modelled with giant liposomes as membrane models confirmed the hypothesis of the occurrence of a fusion phenomenon between the nanovectors and cell membranes. This process highlights the potential of catanionic vesicles for a future pharmaceutical application as a universal drug delivery system.