The Effect Of Physicochemical Property On The Transport Mechanism Of Solid Lipid Nanoparticles

Solid lipid nanoparticles have gained much attention because of its low toxicity and high stability in recent years.It is believed to be the most promising drug delivery system for clinical applications.By modifying the structure of the solid lipid nanoparticles,the absorption and the bioavailability of drugs can be improved.Therefore,it is helpful for us to design the proper carriers which have high transport efficiency by studying the relationship between the physicochemical properties of the solid lipid nanoparticles and the transport mechanism in cells.The research studied the relationship between the physicochemical properties of solid lipid nanoparticles and the transmembrane transport mechanism,and analyzed the advantage pathways which different nanoparticles depended on during the transportation.Glycerin monestearin,glycerol tristearate and glycerin monobehenate were used as the lipid materials to prepare the solid lipid nanoparticles by solvent diffusion method.Otcadecylamine-fluorescein isothiocyanate(ODA-FITC)were synthesized to be used as the fluorescence marker.The particle size and the surface charge of the three nanoparticles were detected to be similar.Transmission electron microscopy(TEM)was used to observe the nanoparticles directly.MDCK cells were used as the model cell to prove the safety of all the nanoparticles.By incubating the cell and the cell monolayer with low temperature and different cell inhibitors,the transport mechanism of the nanoparticles were studied.The stability of the solid lipid nanoparticles during the transportation was observed by FRET.The distribution of the nanoparticles in the different cell organelles were studied with the cell colocalization experiment.We have found that the amount of the intake of the glycerol tristearate nanoparticle was higher than the other two nanoparticles.After the inhibition of the active transport process,the amount of the internalization of the solid lipid nanoparticles with moderate oil-water partition coefficient was the highest among the three nanoparticles.After the uptake pathways suppressed with various inhibitors,we can observed that glycerol tristearate solid lipid nanoparticles were more dependent on the lipid raft/caveolae pathway while glycerin monobehenate were easier to be absorbed via clathrin-related pathway.The amount of the transcytosis of the three solid lipid nanoparticle was similar while the amount of glycerol tristearate nanoparticle across the cell monolayer was the highest in low temperature condition.The glycerol tristearate solid lipid nanoparticles were more depended on the endoplasmic reticulum to Golgi complex pathway.The nanoparticles remained steady during the uptake and the transportation process.The colocalization study showed that the glycerol tristearate nanoparticle entered the endoplasmic reticulum more readily.All the three nanoparticles had a large distribution in lysosome,endosome,endoplasmic reticulum and Golgi complex.Solid lipid nanoparticles were prepared by solvent diffusion method with glycerol tristearate and different amount of PEG2000-SA for hydrophilic modification.The difference between the amount of intake of the nanoparticle was performed by using low temperature and the advantage uptake pathways of the different nanoparticles were studied by using the cell inhibitors.The results showed that although the PEG modification could decrease the amount of the internalization of nanoparticles to a certain extent,the amount of the transportation of the nanoparticles across the cell monolayer could be increased.The mechanism research showed that the PEG modification would increase the amount of the nanoparticles in Golgi complex by avoiding the transport process into the endoplasmic reticulum,which resulted in the increment of the amount of transportation.Our research may be helpful to guide the prescription design and structural modification in order to construct the ideal carriers which have the ability to transport more efficiently.