Limits...
Doxorubicin-poly (ethylene glycol)-alendronate self-assembled micelles for targeted therapy of bone metastatic cancer.

Ye WL, Zhao YP, Li HQ, Na R, Li F, Mei QB, Zhao MG, Zhou SY - Sci Rep (2015)

Bottom Line: In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS.Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX.In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.

ABSTRACT
In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

No MeSH data available.


Related in: MedlinePlus

Accumulative release characteristics of DOX from DOX loaded DOX-hyd-PEG-ALN micelle at different pH medium (A). Data are presented as the average ± standard deviation (n = 3). *P < 0.05 vs pH7.4; #P < 0.05 vs pH6.5. Binding kinetics of DOX, DOX loaded DOX-hyd-PEG micelle and DOX loaded DOX-hyd-PEG-ALN micelle with the HA (B). Data are presented as the average ± standard deviation (n = 3). *P < 0.05 vs DOX; #P < 0.05 vs DOX-loaded DOX-hyd-PEG micelles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4588583&req=5

f6: Accumulative release characteristics of DOX from DOX loaded DOX-hyd-PEG-ALN micelle at different pH medium (A). Data are presented as the average ± standard deviation (n = 3). *P < 0.05 vs pH7.4; #P < 0.05 vs pH6.5. Binding kinetics of DOX, DOX loaded DOX-hyd-PEG micelle and DOX loaded DOX-hyd-PEG-ALN micelle with the HA (B). Data are presented as the average ± standard deviation (n = 3). *P < 0.05 vs DOX; #P < 0.05 vs DOX-loaded DOX-hyd-PEG micelles.

Mentions: The drug release behavior of the DOX loaded DOX-hyd-PEG-ALN micelle was investigated under a simulated physiological condition (pH 7.4) and an acidic microenvironment (pH 6.5 and 5.0) at 37 °C. As showed in Fig. 6A, the speed and amount of DOX released from the DOX loaded DOX-hyd-PEG-ALN micelle was strongly dependent on pH value. DOX loaded DOX-hyd-PEG-ALN micelle released DOX faster at pH 5.0 and 6.5 than at pH 7.4. The faster release of DOX from the DOX loaded DOX-hyd-PEG-ALN micelle in acidic environment was due to the acid-cleavable characteristics of the hydrazone bond in micellar material. It was expected that the DOX loaded DOX-hyd-PEG-ALN micelle was stable in blood circulation and accumulated in tumor tissue through EPR effect. Once in endolysosome of tumor cells, the DOX was released out from DOX loaded DOX-hyd-PEG-ALN micelle because of the acidic microenvironment of endolysosome, and DOX subsequently diffused into the cytoplasma of tumor cells and trafficked to the nucleus55.


Doxorubicin-poly (ethylene glycol)-alendronate self-assembled micelles for targeted therapy of bone metastatic cancer.

Ye WL, Zhao YP, Li HQ, Na R, Li F, Mei QB, Zhao MG, Zhou SY - Sci Rep (2015)

Accumulative release characteristics of DOX from DOX loaded DOX-hyd-PEG-ALN micelle at different pH medium (A). Data are presented as the average ± standard deviation (n = 3). *P < 0.05 vs pH7.4; #P < 0.05 vs pH6.5. Binding kinetics of DOX, DOX loaded DOX-hyd-PEG micelle and DOX loaded DOX-hyd-PEG-ALN micelle with the HA (B). Data are presented as the average ± standard deviation (n = 3). *P < 0.05 vs DOX; #P < 0.05 vs DOX-loaded DOX-hyd-PEG micelles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588583&req=5

f6: Accumulative release characteristics of DOX from DOX loaded DOX-hyd-PEG-ALN micelle at different pH medium (A). Data are presented as the average ± standard deviation (n = 3). *P < 0.05 vs pH7.4; #P < 0.05 vs pH6.5. Binding kinetics of DOX, DOX loaded DOX-hyd-PEG micelle and DOX loaded DOX-hyd-PEG-ALN micelle with the HA (B). Data are presented as the average ± standard deviation (n = 3). *P < 0.05 vs DOX; #P < 0.05 vs DOX-loaded DOX-hyd-PEG micelles.
Mentions: The drug release behavior of the DOX loaded DOX-hyd-PEG-ALN micelle was investigated under a simulated physiological condition (pH 7.4) and an acidic microenvironment (pH 6.5 and 5.0) at 37 °C. As showed in Fig. 6A, the speed and amount of DOX released from the DOX loaded DOX-hyd-PEG-ALN micelle was strongly dependent on pH value. DOX loaded DOX-hyd-PEG-ALN micelle released DOX faster at pH 5.0 and 6.5 than at pH 7.4. The faster release of DOX from the DOX loaded DOX-hyd-PEG-ALN micelle in acidic environment was due to the acid-cleavable characteristics of the hydrazone bond in micellar material. It was expected that the DOX loaded DOX-hyd-PEG-ALN micelle was stable in blood circulation and accumulated in tumor tissue through EPR effect. Once in endolysosome of tumor cells, the DOX was released out from DOX loaded DOX-hyd-PEG-ALN micelle because of the acidic microenvironment of endolysosome, and DOX subsequently diffused into the cytoplasma of tumor cells and trafficked to the nucleus55.

Bottom Line: In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS.Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX.In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.

ABSTRACT
In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

No MeSH data available.


Related in: MedlinePlus