Study Of The Preparation And Characters Of Nanostructure Lipid Carriers Containing Paclitaxel

Nanoparticle drug carriers are delivery systems with the diameter from 1 to 1000 nm that composed of drug and excipients. They are well in improving the physical and chemical characters of drug, decreasing the side effect of drug, targeting to the diseased cell and controlling the releasing of drug. Following by the solid lipid nanoparticles (SLNs), the new nanostructure lipid carriers(NLCs) had been developed. NLCs are composed of a solid lipid matrix with a certain content of liquid lipid. The incorporation of liquid lipids to solid lipids leads to great imperfections in the crystal lattice of nanoparticles, as the result, NLCs have much more drug loading capacity and less drug expulsion during storage compared with SLNs. NLCs could be produced on large scale by high pressure homogenization as the preparation of NLCs was more simple. The products might be made into many forms like tablet, pill, capsule or powder for the clinical application.Objective:In present study, we developed a new carrier system of drug-nanostructure lipid particle to delivery paclitaxel for improving the solubility of paclitaxel, increasing the enveloping efficiency and enhancing drug loading capacity.Methods:TAX-NLC was prepared by high pressure homogenization-hot homogenization. The size and distribution was detected by Laser High Performance Particles Sizer. The morphology was observed by Scanning Electron Microscope. The enveloping efficiency and drug loading capacity were determined by HPLC with fluorescence tracer and radionuclide trace technique with ¹²⁵I-paclitaxel tracer. Laser confocal microscopy was used to observe and calculate the cell intaking of TAX-NLC labeled with fluorescence. In addition, the radionuclide trace technique with ¹²⁵I-paclitaxel was used to quantitate the cell intaking of TAX-NLC.Results:NLCs prepared by high pressure homogenization were under 100 nm size. The PDI arranges from 0.30 to 0.60. The best preparation procedure of TAX-NLC according to its characters was like this: paclitaxel, stearic acid, cholesterol, lecithin and corn oil were dissolved in a little organic solvent and stirred uniformly, keeping temperature at 70±5℃to evaporate the solvent and inject the oil state into the aqueous state of the same temperature containing tween-80 (1%) (w/v) under stirring (1200RPM), one hour later, cool to room temperature to obtain the primary emulsion of TAX-NLC. The primary emulsion was homogenized for six cycles under 60 psi and cooled to room temperature to form the aqueous dispersion of TAX-NLC. The average diameter of the TAX-NLC was 66±6 nm(n=3), the average PDI was 0.45±0.02(n=3), the average enveloping efficiency was 68.78% and 81.27%±0.03 (n=28), and the drug loading capacity was 1.44 %81.27%±0.0 (n=3). By the laser confocal microscopy, the endocelluar fluorescence intensity increased along with the time after adding TAX-NLC labeled with fluorescence, and reached highest level or saturation state in 2 hours. At the early stage, the TAX-NLC labeled with fluorescence was transported into the cells and distributed around the inner wall of cellular membrane, 2-3 hours later, it was assembled to be high bright block on the side of cell. This indicated that the transportation into cell of TAX-NLC might be an active process and the mechanism should be studied in future. The cell intaking rate of TAX-NLC had been calculated, at the saturated state, there were about 180,000,000 molecules of paclitaxel be transported into one cell, and the concentration of paclitaxel in cell was higher 29 times than the outside. This may qualify the need for chemotherapy of tumor cells.Conclusion: The TAX-NLC in present study was a perspective carrier system.