| BackgroundIn recent year, liposome drug delivery system was much concerned because of its excellent biocompatibility. Liposomes have many advantages, such as targeted, controlled release, high biocompatibility and low toxicity etc. But liposomes is difficult to use in clinic and the controllability is poor.Take the paclitaxel liposome for example, which has lunched in many countries. The paclitaxel liposome is add to a bottle with 10ml 5% glucose solution.then shake the bottle with a dedicated oscillator (oscillation frequency of 20Hz, amplitude: X-axis direction 7cm, Y axis 7cm, Z axis 4cm) for 5 minutes, then further dilution.In our early research, docetaxel liposomes(DOT-LP) was prepared by the patent technology(Application No: 200910103135.X; Application No: PCT/CN2010/070342) that use the solid dispersion technology together with the effervescent technology. The size of the liposome is about 0.8μm ,with a negative charge.The docetaxel liposomes could solve the problems mentioned above.The experiments in vivo on rabbits showed that the 92% docetaxel was dlivered to lung,little to liver, kidney and other organs.We published two papers,one in Journal of Pharmaceutical and Biomedical Analysis(2009,49(2):989-996,IF:2.8)and the other in Journal of Drug Targeting,(2010, 4,PMID: 20429774). ObjectiveAim to solve the problems mentioned above, use DOT as a model drug in order to further improve the development of DOT-LP process and simplify the operation in clinic of liposome.Also provide theoretical basis for the clinical application of liposome delivery systems.Method1. The DBaumNC technology was used to prepare DOT-LP.First, the solid dispersion technology was used to prepare DOT-PLP, and then, DOT-LP were obtained from DOT-PLP by effervescent technology after solidify.2. The morphology of liposomes was observed by the light microscopy, the particle size and zeta-potential were determined by Malvern ZEN3600.3. Entrapment efficiency of DOT-LP were studied by protamine precipitation.HPLC analysis method was established for analysis of DOT-LP.4. The significant influence factors on preparation of DOT-LP were studied using single factor method with proliposome hydration time and morphology of liposome as index.5. The formulation and preparation of DOT-LP was optimized and initial determined using orthogonal designResult1. Formulation and preparation study: According to single factor , proliposome hydration time and morphology of liposome was much significant effected by reaction tenperature and time ,DOT consumption etc.2. The optimum formulation and preparation was obtained by orthogonal experiment which was based on the single factor. The resulted DOT-PLP were white powder. After the emulsion, it become homogeneous hydration. The resulted DOT-LP were round in shape and dispersed well.3. Quality study: The study of quality of samples prepared by the best formulation and preparation showed that the DOT-PLP had good flow property and were completely hydrated with 5% sodium bicarbonate solution for 3min. The pH value of the resulted DOT-LP ranged from 5.3 to 5.5. The liposomes were round and dispersed well. The particle size, zeta-potential and entrapment efficiency were 1.2μm, -15.3mv and 90.5%.Conclusion1. The preparation technology in this paper has many advantages,such as simple operation,easy to control the conditions, stable quality and so on.It has good industrial prospect.2. The docetaxel liposomes which was obtained by the ultimate prescription and prosess only need to add some effervescent agent and shake with hand before clinic use. The special devices is unnecessary.it has a good clinic use prospect. |
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