Abstract
Though liposome-based drugs are in clinical use, the mechanism of cell internalization of liposomes is yet an object of controversy. The present experimental investigation, carried out on human glioblastoma cells, indicated different internalization routes for two diastereomeric liposomes. Molecular dynamics simulations of the lipid bilayers of the two formulations indicated that the different stereochemistry of a lipid component controls some parameters such as area per lipid molecule and fluidity of lipid membranes, surface potential and water organization at the lipid/water interface, all of which affect the interaction with biomolecules and cell components.
Highlights
The development of liposome technology has grown fast in the last 20–25 years, and a number of liposome-based drugs were approved for clinical use and more are in various phases of clinical trials.[1,2,3,4,5] the parameters that control the interaction of these lipid vesicles with biological molecules and their biological targets, the uptake of their payloads and, their efficacy, are not fully elucidated
Molecular dynamics simulations of the lipid bilayers of the two formulations indicated that the different stereochemistry of a lipid component controls some parameters such as area per lipid molecule and fluidity of lipid membranes, surface potential and water organization at the lipid/water interface, all of which affect the interaction with biomolecules and cell components
Multiple pathways of internalization have been described for liposomes such as fusion with the cell membrane, exchange of lipids with the plasma membrane and endocytosis,[6,13,14,15] all of which were affected by liposome physicochemical features
Summary
The development of liposome technology has grown fast in the last 20–25 years, and a number of liposome-based drugs were approved for clinical use and more are in various phases of clinical trials.[1,2,3,4,5] the parameters that control the interaction of these lipid vesicles with biological molecules and their biological targets, the uptake of their payloads and, their efficacy, are not fully elucidated. It was reported that the lipid composition, vesicle size, surface electrical features and fluidity/rigidity of lipid membranes control the interaction with cells and the pathway of internalization.[6,7] Once in the biological environment, liposomes interact with surrounding biomolecules, which adsorb on their surface and form a biomolecular corona that might affect targeting.[8] the water bound to the surface of biomembranes typically called “glassy” or “biological water” plays a critical role in the. We previously reported that liposomes composed of dimyristoyl-sn-glycero-phosphocholine, DMPC, and one of the two diastereomeric cationic gemini amphiphiles, 1a or 1b (Fig. 1), showed different efficacy in the delivery of the photosensitizer meta-tetrahydroxyphenylchlorin (m-THPC) to malignant glioma cells, DMPC/1b liposomes being more efficient than DMPC/1a liposomes.[12] it was found that the different stereochemistry of the gemini component controls the intracellular distribution of m-THPC.[12] These findings strongly suggest that the ‘diastereomeric’ liposomes might follow different pathways of internalization
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