- PURPOSE: The in vitro inhibitory effect of Docetaxel (DTX) and Everolimus (EVR) alone and together in
poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) nanocarriers on angiogenic
processes and acute toxicity in mice was evaluated.
METHODS: PEG-b-PLA DTX and/or EVR nanocarriers were characterized for size, drug loading, stability,
and drug release. Cell proliferation, tubule formation, and migration studies were performed in
Human Umbilical Vein Endothelial Cells (HUVEC) and Maximum Tolerated Doses (MTD)
studies were in mice.
RESULTS: DTX and EVR loading was 1.93 and 2.00 mg/mL respectively with similar solubilities for dual-drug
micelles. All micelles were below 30 nm with diffusion controlled drug release. The IC[subscript 50s]
for DTX, EVR micelles were, 6.80 ± 0.67, 18.57 ± 2.86 and 0.65 ± 0.11 nM respectively with a
synergistic inhibitory effect for dual-drug nanocarriers. Significant inhibition of tube formation
occurred upon treatment with dual-drug nanocarriers as compared to individual micelles. EVR
presence in dual-drug nanocarriers was able to significantly increase the inhibition of the
migration of HUVEC by DTX. The MTDs for EVR, DTX and dual-drug micelles were 50, 30
and 20 mg/kg for each respectively.
CONCLUSIONS: DTX-EVR dual-drug nanocarriers have antiangiogenic effects in vitro mediated through cellular
angiogenic process and possess clinically relevant MTD.
- Mishra, G. P., Doddapaneni, B. S., Nguyen, D., & Alani, A. W. (2014). Antiangiogenic Effect of Docetaxel and Everolimus as Individual and Dual-Drug-Loaded Micellar Nanocarriers. Pharmaceutical Research, 31(3), 660-669. doi:10.1007/s11095-013-1188-z
|Funding Statement (additional comments about funding)
- This study was supported by the grant from AACP New Pharmacy Faculty Research Award
Program, Medical Research Foundation of Oregon New Investigator Grant and Oregon State