Preparation And Evaluation Of Paclitaxel Nano-liposomes Gels

Objective:To prepare the paclitaxel nano-liposomes gels, study the analgesic and anti-inflammatory effects? In order to provide the experimental basis for the development of new formulations of paclitaxel in the treatment of rheumatoid arthritis.Methods:1.To set up the HPLC chromatography method measuring paclitaxel, and establish the method of the entrapment efficiency of the paclitaxel nano-liposomes.2. Paclitaxel nano-liposomes were prepared using thin film evaporation high pressure microfluidization, freeze dried to powder, and the optimal method was determined by the orthogonal test. The shape, size, size distribution were detected by transmission electron microscope (TEM), nano-particle size analyzer, respectively.3.Viscosity, color, matrix spread and uniformity as observation indexes to determine the best matrix of paclitaxel nano-liposomes gels, and the optimal method was determined by the orthogonal test. Mixed carbomer to prepare the paclitaxel nano-liposomes gels and studied its stability. Adopting membrane diffusion method to study the release of nano-liposomes gels.Using Franz Diffusion Cell and rats to investigate transdermal diffusion characteristics of the modified nano-liposomes gels in vitro.Study on the drug distributes throughout the skin of mice.4. Observe the paclitaxel nano-liposomes gels’ skin irritation and its effect on mouse inflammatory model induced by Carrageenin and the pain model induced by formaldehyde.Result:1.To establish the HPLC chromatography method to determine the paclitaxel, which is simple, feasible and convenient to operation. The method for the determination of entrapment efficiency was confirmed.2. The optimal formulation and preparing conditions of paclitaxel nano-liposomes were as the following:the content of lecithin was 2%, drug:lecithin=1:30, lecithin:cholesterin= 10:1.The particle size of the liposome prepared was 81.8nm; The particle size distribution coefficient was 0.18. The average entrapment efficiency of the liposomes was up to 73.2%. The shape of nano-liposomes were circular or spherical, well dispersed, with obvious fingerprint shaped structure.3. The best matrix was carbomer.The optimal formulation and preparing conditions of paclitaxel nano-liposomes gels were as the following:carbomer 3%, glycerol5%, azone3%. The release amount of nano-liposomes gels was 79.04% at 72h and the cumulative penetration amount per unit area was 429.68μg.cm-2 at 48h.Compared with paclitaxel gels, paclitaxel nano-liposomes gels can significantly promote the paclitaxel through the skin (P<0.05).The content of paclitaxel in the stratum comeum and active skin layer is respectively 3.41 and 5.35μg.cm-2 at 4h.Compared with paclitaxel gels, paclitaxel nano-liposomes gels can significantly improve the retention of the drug in the skinAThe result of skin irritation experiment proved that the gels showed no irritancy on skin.In inflammatory experiment, compared with the model group, paclitaxel nano-liposomes gels produced significant inhibition on rat paw edema in a dose-dependent manner (P<0.05). In mouse formalin test, paclitaxel nano-liposomes gels reduced the number of writhing induced by acetic acid, significantly (P<0.05).Conclution:This preparation is prepared with simple technology. The particle sizes are smaller and uniform. Nano-liposomes gels featured a sustained release in vitro, the nano-liposomes could improve the retention of the drug in the skin and increase diffusion rate of paclitaxel through the skin of rats compared with paclitaxel gels. Paclitaxel nano-liposomes gels have significant analgesic and anti-inflammatory effects.