Study On The Preparation Technology Of Docetaxel Nanoparticles Based On Two Shaped Polymers

Docetaxel(DTX)is a first-line taxane anti-cancer drug with broad-spectrum anti-tumor activity,but it has problems of low solubility,poor stability,poor tumor selectivity,high toxic and side effects.In this study,docetaxel nanoparticles were prepared in order to find a new drug delivery system for insoluble anti-tumor drugs based on the solution of DTX insoluble.DTX nanoparticles were prepared by anti-solvent precipitation combined with high pressure homogenization using two shapes hydrophilic polymers(G2 and PEG2000)and amphiphilic polymers(G2-C18 and PEG2000-C18)as carriers respectively.The particle size and morphology were investigated by dynamic light scattering and transmission electron microscopy.Drug release in vitro and hemolysis were studied.In addition,anti-tumor effects were examined by cytotoxicity,cell uptake,and in vivo efficacy experiments.In the first part,the results showed that the particle size of DTX/G2 nanoparticles was(356.8 ± 6.71)nm,the drug loading was(62.3 ± 1.9)%,and the particle size of DTX/PEG2000 nanoparticles was(602.5±21.6)nm,the drug loading was(59.9 ± 1.1)%,meanwhile,both nanoparticles were flaky by SEM.The two nanoparticles released slowly in vitro with a cumulative release rate of 80.4%and 88.6%at 192h,and the hemolytic rate was less than 5%.MTT results showed that DTX/G2 nanoparticles had higher cytotoxicity compared to DTX/PEG2000 nanoparticles(IC50,2.374 vs 4.385 ?g/mL).Cellular uptake results showed that DTX/G2 nanoparticles had a higher cellular uptake rate compared to DTX/PEG2000 nanoparticles(20.46 vs 19.67%).In vivo efficacy experiments,DTX/G2 nanoparticles have a higher tumor inhibition rate compared to DTX/PEG2000 nanoparticles(75.7 vs 67.7%).It can be seen that DTX/G2 nanoparticles exhibit stronger anti-tumor effects than DTX/PEG2000 nanoparticles.In the second part,the results showed that the particle size of DTX/G2-C8 nanoparticles was(322.3 ± 8.87)nm,the drug loading was(72.2±0.6)%,and the particle size of DTX/PEG2000-C18 nanoparticles was(390.0±16.2)nm,the drug loading was(67.7±1.7)%,meanwhile,both nanoparticles were spherical by TEM.The two nanoparticles released slowly in vitro with a cumulative release rate of 87.0%and 89.6%at 192h,and the hemolysis rate meets the needs of intravenous administration.MTT results showed that DTX/G2-C18 nanoparticles had higher cytotoxicity compared to DTX/PEG2000-C18 nanoparticles(IC50,1.716 vs 2.616 ?g/mL).Cellular uptake results showed that DTX/G2-C18 nanoparticles had a higher cellular uptake rate compared to DTX/PEG2000-C18 nanoparticles(28.99 vs 23.02%).In vivo efficacy experiments.DTX/G2-C18 nanoparticles have a higher tumor inhibition rate compared to DTX/PEG2000-C18 nanoparticles(83.2 vs 77.7%).It can be seen that DTX/G2-C18 nanoparticles exhibit stronger anti-tumor effects than DTX/PEG2000-C18 nanoparticles.In conclusion,the docetaxel nanoparticles prepared by dendritic polymers(G2-C18,G2)have a stronger anti-tumor effect than the chain polymers(PEG2000-C18,PEG2000),the docetaxel nanoparticles prepared by amphiphilic polymers have a stronger anti-tumor effect than the hydrophilic polymers,and the anti-tumor effect of DTX/G2-C18 nanoparticles is the strongest.It is indicated that the morphology of polymer plays a key role in affecting cellular uptake and anti-tumor activity.In the research of new nanoscale drug delivery system,the morphology of polymer should be considered to improve the curative effect of cancer therapy.