Hyaluronic Acid Modified RG3-NLC Nanometer Medicine System Preliminary Study

This experiment on the physical and chemical properties of anti-cancer drugs Rg3 ginsenosides and pharmacological properties, launched from preparation to the study of nature, to pharmacokinetic and targeted research on a series of discussion. And obtained sufficient theoretical basis to support after hyaluronic acid modified Rg3-NLC has a certain tumor targeting property, and for the dosage form of follow-up study to lay the foundation.1.In oleic acid and glycerin monostearate these two injections are commonly used matrix with CTAB this cationic emulsifier, solvent by ultrasonic dispersion prepared Rg3-NLC after modification of hyaluronic acid ultimately the purpose of this experiment was made by the dosage form, namely the HA-Rg3-NLC. Measured grain size of 165±3.84 nm, zate potential-22.87±0.97 mv, in terms of glucan gel chromatography the average packet encapsulation efficiency and drug loadings were 65.33% and 8.37%, respectively, PDI was 0.227±0.001. Respectively, with 5% of the freeze effect best, sucrose and mannitol do finished product rendering white powder, good appearance, all the indexes meet the requirements after dissolved.2.The HA-Rg3-NLC nanoparticles avoiding cold and release characteristics of nanoparticles itself made a further study. Frozen one with the appearance of the roundness, particle size of under 200 nm, potential, coating rate and drug loadings and PDI are compared with the form, the basic no change, visible frozen one with nature is stable. In vitro study, with 30% of the PBS as a release of medium carrier and drug is stable, on this condition the release rule in Higuchi equation, and through the alignment with the solution set of the HA-Rg3-NLC nanoparticles have certain sustained-release effect.3.through rat in vivo pharmacokinetic study, this paper discusses the distribution process of nanoparticles in the body, comparing with the solution set, found drugs into nanoparticles significantly prolonged the after time in vivo, effectively avoid the ginseng saponin Rg3 this fat-soluble drugs, low bioavailability and retention period of weakness, so as to achieve the effect of long cycle.4.Through a tumor-burdened mice tissue distribution study and fluorescence in fact evidence of confocal microscope, proved with hyaluronic acid modified Rg3 ginsenosides has a certain tumor targeting property. Analysis of the causes may be due to the HA-Rg3-NLC in encountered in the circulation of the blood after high expression HA receptor of tumor cells, and the specificity of combination, and stays within the tumor tissues so as to achieve a certain target effect, also may be a tumor tissue itself is a rich blood supply of the organization, large amount of blood relationship to improve the chances of contact with the HA receptor, thus mediated targeted. In addition to the tumor tissue, liver and large volume of drugs, the reason is nanoparticles size after the formation of about 150 nm, which makes the body put it as a foreign body and macrophage, macrophages after being swallowed has lost its activity, and together with the pass to the metabolism of liver cells, which is lead to liver cells have become the biggest medicated important factors of the organization.Through a confocal microscope imaging system, we can clearly see the liver cells, as well as the dot nanoparticles. Due to the irregular arrangement of tumor cell, cell small and irregular, so it is very difficult for us to find in the perspective of the fixed magnification clear outline tumor cells and the spatial location of nanoparticles and tumor cells, so, in this experiment can be observed, nanoparticles in liver cells across the plasma membrane, to infer the HA-Rg3-NLC transshipment of nanoparticles in cancer cells. We can see clearly that punctiform nanoparticles by intercellular space in a few hours to the cell membrane in the process of operation, once arrived in liver cells, will soon be back decomposition, large particles small, small particles without, at last a single cells are present weak fluorescence, the contour is clear, this shows that the destruction of the drug and its carrier and degradation must be happened in a cell. Internal biochemical reactions and tumor cells, and also do such speculation.To sum up, this experiment study the successful preparation of HA-Rg3-NLC nanoparticles, and build on the nanoparticles drug delivery system. Preliminary explored in NLC coating as the carrier of fat soluble drugs and drug release regularity, studies have shown that the HA-Rg3-NLC nanoparticles to improve the bioavailability of the drugs, increased the drug in the body, retention time, and played a slow release effect, its mechanism may be due to the carrier frame protection, avoid the drugs and enzymes in biological samples such as contact and not be concerned by the catabolism of soon, in the process of release is through diffusion release of release and decomposition process, a little bit of exposure to drugs and to achieve long cycle and slow release. Targeted research has shown that the HA-Rg3-NLC nanoparticles can be targeted to the tumor and the liver, and can be a very good targeted to cells.