The therapeutic application of deoxypodophyllotoxin(DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers(m PEG-PDLLA) were co...The therapeutic application of deoxypodophyllotoxin(DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers(m PEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg m PEG-PDLLA, the weight ratio of 1 : 4(m PEG-PDLLA : DPT), 30 m L hydration volume and the hydration temperature at 40 oC. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles(DPT-PM) were about(20 ± 2.84)% and(98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10^(-7) mol·L^(-1), which showed significant difference from free DPT(P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.展开更多
基金supported by the Ministry of Science and Technology of China(No.2014ZX09507001006)the National Natural Science Foundation of China(No.81501579)+2 种基金the Natural Science Foundation of Jiangsu Province(No.BK20150702)the Science and Technology Development Fund of Nanjing Medical University(No.2016NJMU105)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘The therapeutic application of deoxypodophyllotoxin(DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers(m PEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg m PEG-PDLLA, the weight ratio of 1 : 4(m PEG-PDLLA : DPT), 30 m L hydration volume and the hydration temperature at 40 oC. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles(DPT-PM) were about(20 ± 2.84)% and(98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10^(-7) mol·L^(-1), which showed significant difference from free DPT(P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.
