How do the physicochemical properties of nanoliposomes affect their interactions with the hCMEC/D3 cellular model of the BBB?
Nanosized liposomes composed of 1,2-distearoyl-sn-glycerol-3-phosphatidylcholine (DSPC), cholesterol and polyethylene glycol-conjugated phospholipid (PEG), incorporating FITC-dextran (FITC) and in some cases also Rhodamine-conjugated phospholipid (RHO) (as labels) were constructed by the thin film hydration method, followed by extrusion; membranes with pore diameters from 50 to 400nm were used, while charged vesicles were produced by partially replacing DSPC with 1,2-distearoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DSPG). The uptake of liposomes by hCMED/D3 cells was evaluated by measuring FITC in cells, and their permeability across cell monolayers was evaluated, by measuring the FI of liposome associated-FITC and RHO in the receiving side of a monolayer-transwell system. Results prove that liposome size has a significant effect on their uptake and permeability (for both charged and non-charged vesicles). The effect of liposome charge on cell uptake was slight (but significant), however charge (in the range from -2 to -16mV) did not significantly affect vesicle permeability; a significant decrease was only demonstrated for the liposome with the highest charge.
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26504, Greece.
Konstantina
K
Papadia
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26504, Greece.
Eleni
E
Markoutsa
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26504, Greece; Institute of Chemical Engineering, FORTH/ICE-HT, Rio 26504, Greece. Electronic address: santimis@upatras.gr.
Sophia G
SG
Antimisiaris
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism*; D010316:Particle Size; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012235:Rhodamines / Q000737:chemistry; D013499:Surface Properties
D003911:Dextrans; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010743:Phospholipids; D012235:Rhodamines; D011092:Polyethylene Glycols; C084352:distearoyl phosphatidylglycerol; D002784:Cholesterol; C010942:1,2-distearoyllecithin; D016650:Fluorescein-5-isothiocyanate
BBB; Cell model; Charge; Liposomes; Nanoparticle; Permeability; Size; Uptake; hCMEC/D3