The Research And Preparation Of Docetaxel Niosome

Docetaxel is a recent development of new generation taxane antitumor agents. Because of bad water-soluble, the current docetaxel injections are the concentrated liquid that Tween -80 was used as solvent and a 13% ethanol solvent was also equipped with. Tween-80 is hemolytic and sticky, so it is easy to produce allergic reactions, to cause inconvenience to the clinical use of docetaxel. Niosomes is one kind of vesicle drug carriers that use surfactants as membranes material with a closed vesicle structure. It can significantly improve the pharmacokinetics of drug characteristics and in vivo tissue distribution. The stability of niosomes is higher than it of liposomes. The materials those are used for niosomes are cheaper than those for liposomes. This research is about preparation of docetaxel niosomes. Span, Solutol such as surfactants were used as the membranes material. Docetaxel niosomes suspension was prepared by ethanol injection. Mannitol, trehalose were used as freeze-dried scaffold agents. The suspension was freeze-dried into a lyophilized.The determination of docetaxel was setted up by HPLC. The HPLC was for the determination of concentration, entrapment efficiency, release rate of docetaxel niosomes and a analytical method for in vivo process was established. Sephadex G-50 gel column chromatography, dialysis, ultracentrifugation, ultrafiltration centrifugal method were compared for determining the entrapment efficiency of docetaxel niosome. Sephadex G-50 gel column chromatography was used as an initial screening of entrapment efficiency. Ultrafiltration centrifugation was used to determine the entrapment efficiency of the final product. The positive phase dialysis and reversed-phase dialysis was compared for studying the in vitro release characteristics of the niosomes . Reversed-phase dialysis method was selected for testing the release properties of niosomes finally. The results show that in 1h, whether niosomes suspension or lyophilized niosomes their accumulation drug release was less than 40%. The accumulation drug release is fitting the first order equation. The preparation process of niosomes was optimized. The impacts of lyophilized in freeze-dried nisomes were inspected under entrapment efficiency for the target in combination with the effect of freeze-dried.The membranes and the volume of the main medicinal factors such as the impacts on the entrapmet efficiency were inspected. By orthogonal design and the effect of freeze-dried the best prescription was selected as Span40: Span60 = 3:1, Span: Solutol HS 15 = 2:1, Lipoidica: cholesterol = 20:1, Lipoidica: Docetaxel = 10:1. The niosomes suspension was prepared of this prescription with high entrapment efficiency. At the same time the lyophilized niosomes was prepareed with good appearance and re-dispersion. The particle size and size distribution was determined by laser light scattering and its influencing factors were studied. The results showed that high concentration of docetaxel has larger diameter. The low concentration of docetaxel has small particle size. The size and distribution were increase after lyophilized niosomes was re-dispersion by saline solution. At the same time, the entrapment efficiency was reduced at about 10%. The freeze-dried niosomes was under 4500XL , 40℃, with a relative humidity of 60% can stay stability exist within 60 days.The docetaxel niosomes in tissue distribution and pharmacokinetic were studies under docetaxel injection as control. The results show that: the docetaxel niosomes and docetaxel injection were given by rat tail vein injection. In rat organ distribution of all there is significant difference. Docetaxel nisomes gathered at the lungs. Concentration was significantly higher in lung than it was in other organizations, so it has a good target at lung. The drug concentration after administration of niosomes in blood has a much slower rate at elimination.In this issue the docetaxel niosomes was prepared by useing surfactants as membranes such as Span, Solutol. The technology was feasible, and the product meets the principles about vesicles by Pharmacopoeia. The docetaxel pharmacokinetics was significantly changed when the doctaxel was prepared as a niosomes. It provided a reference value for the preparation of a stealth niosomes or other targeted niosomes.