Preparation And Evaluation Of Albumin-Paclitaxel Tumor Targeted Nano-Micelle Formulation

Tumor targeted drug delivery system （TTDDS） is the hotspot of development of anti-tumor drug’s new formulation.Now FDA has approved a new formulation of paclitaxel: Abraxane, which contains the human serum albumin. Clinical studies have shown that the formulation is very effective and safe without allergic reactions and neurotoxicity and has tumor targeted property. However Abraxane’albumin dosage is large and the preparation process is complex so that the cost is extremely high. Our study is to develop a new tumor targeted formulation of paclitaxel while reducing the dosage of albumin and simplifying the preparation process which can result in cutting down the cost.Firstly, in this study, paclitaxel nano-micelle （PTX NM） was first developped. Albumin was added as modification material in the basis of this formulation, albumin paclitaxel nano-micelle （HSA-PTX NM） was then developped. Particle Size Analyzer was used to screen the preparation of which the particle size was about 100 nm diameters. Scanning electronic microscope showed the lyophilized powder dispersed homogeneously without agglomeration. The solution looked transparent after diluted by water. Transmission electronic microscopy revealed particles appeared spherical.Secondly,the anti-tumor effect in vitro of HSA-PTX NM was initially evaluated.MTT results showed that HSA-PTX NM’s inhibition rate on Hela cells’proliferation was higher than commercially available paclitaxel （PTX injection） and have significant difference at 20 mg·L^-1（P<0.05）. At the same time, MTT test showed HSA-PTX NM carrier has lower toxicity than PTX injection.Thirdly, the anti-tumor effect in vivo of HSA-PTX NM was evaluated by pharmacodynamics experiments. Traditional anti-tumor experiments showed that PTX NM’s tumor weight inhibiton rate was 47% while the PTX injection was 20%; HSA-PTX NM’s tumor volume inhibition rate was 67% while the PTX injection was only 15% （P<0.05）.In vivo imaging technology was also used to evaluate the anti-tumor effect. It showed HSA-PTX NM inhibition rate was 72.92%, higher than PTX NM （66.49%） and PTX injection （47.68%）（P<0.05）.The traditional caliper measurement method showed consistent results. The survival time test of bearing B16 melanoma cell C57 mice showed that HSA-PTX NM （24.86 d） can more effectively extend the average survival time of mice than PTX NM （21.42 d） and PTX injection （22.43 d） which had once again proven HSA- PTX NM’s safety and efficacy.Lastly, the distribution property was investigated to verify the reason that HSA-PTX NM was better than PTX NM due to tumor targeted effect of albumin. HPLC technology was used to determine the distribution of paclitaxel in different organ of mice. Results showed the distribution of paclitaxel in the heart, HSA-PTX NM was less than PTX injection at 1 hr（P<0.05）, the distribution of paclitaxel in the tumor, HSA-PTX NM was more than PTX injection at 4 hr and 8 hr（P<0.05）. The distribution property of pactaxel in mice was also measured by in vivo imaging technology. It verified the results that HSA-PTX NM had better tumor targeted property again.In conclusion, a new tumor targeted formulation of albumin-paclitaxel was developed successfully. It showed good anti-tumor effect ant tumor targeted property.