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Delivery of baicalein and paclitaxel using self-assembled nanoparticles: synergistic antitumor effect in vitro and in vivo.

Wang W, Xi M, Duan X, Wang Y, Kong F - Int J Nanomedicine (2015)

Bottom Line: Combination anticancer therapy is promising to generate synergistic anticancer effects to maximize the treatment effect and overcome multidrug resistance.The PTX-BCL NPs displayed remarkably better antitumor activity over a wide range of drug concentrations, and showed an obvious synergism effect with CI50 values of 0.707 and 0.513, indicating that double-ligand modification and the co-delivery of PTX and BCL prodrugs with self-assembled NPs had remarkable superiority over other formulations.Enhanced synergistic anticancer effects were achieved by PTX-BCL NPs, and multidrug resistance of PTX was overcome by this promising targeted nanomedicine.

View Article: PubMed Central - PubMed

Affiliation: Department of Chinese Medicine Integrated Traditional Chinese Medicine and Western Medicine, General Hospital of Ji'nan Command, People's Liberation Army, Ji'nan, People's Republic of China.

ABSTRACT

Purpose: Combination anticancer therapy is promising to generate synergistic anticancer effects to maximize the treatment effect and overcome multidrug resistance. The aim of the study reported here was to develop multifunctional, dual-ligand, modified, self-assembled nanoparticles (NPs) for the combination delivery of baicalein (BCL) and paclitaxel (PTX) prodrugs.

Methods: Prodrug of PTX and prodrug of BCL, containing dual-targeted ligands of folate (FA) and hyaluronic acid (HA), were synthesized. Multifunctional self-assembled NPs for combination delivery of PTX prodrug and BCL prodrug (PTX-BCL) were prepared and the synergistic antitumor effect was evaluated in vitro and in vivo. The in vitro transfection efficiency of the novel modified vectors was evaluated in human lung cancer A549 cells and drug-resistant lung cancer A549/PTX cells. The in vivo antitumor efficiency and systemic toxicity of different formulations were further investigated in mice bearing A549/PTX drug-resistant human lung cancer xenografts.

Results: The size of the PTX-BCL NPs was approximately 90 nm, with a positive zeta potential of +3.3. The PTX-BCL NPs displayed remarkably better antitumor activity over a wide range of drug concentrations, and showed an obvious synergism effect with CI50 values of 0.707 and 0.513, indicating that double-ligand modification and the co-delivery of PTX and BCL prodrugs with self-assembled NPs had remarkable superiority over other formulations.

Conclusion: The prepared PTX-BCL NP drug-delivery system was proven efficient by its targeting of drug-resistant human lung cancer cells and delivering of BCL and PTX prodrugs. Enhanced synergistic anticancer effects were achieved by PTX-BCL NPs, and multidrug resistance of PTX was overcome by this promising targeted nanomedicine.

No MeSH data available.


Related in: MedlinePlus

Transmission electron microscopy imaging of (A) paclitaxel (PTX) nanoparticles (NPs), (B) baicalein (BCL) NPs, and (C) PTX-BCL NPs.
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f3-ijn-10-3737: Transmission electron microscopy imaging of (A) paclitaxel (PTX) nanoparticles (NPs), (B) baicalein (BCL) NPs, and (C) PTX-BCL NPs.

Mentions: PTX-BCL NPs were prepared by the nanoprecipitation method.51 The amphiphilic nature of FA-V-PTX and HA-L-BCL makes it possible for them to self-assemble into NPs with PTX and BCL as the inner core, FA and HA as the hydrophilic shell (Figure 3). Briefly, PLGA (50 mg)-acetone (3 mL) solution was prepared. FA-V-PTX and HA-L-BCL (1/5 and 1/2, wPTX/wBCL) were dissolved in acetone–water solution (50:50, w/w). Then, PLGA, FA-V-PTX, and HA-L-BCL solution were simultaneously and separately added dropwise into the 0.05% poloxamer 188 containing aqueous solution. The mixture was stirred at 600 rpm at RT until complete evaporation of the organic solvent occurred. The redundant stabilizers were removed by centrifugation at 1,000 × g and 4°C for 30 minutes. The pellet was vortexed and resuspended in Milli-Q® water, washed several times, filtered through a 0.45 μm membrane, and adjusted to pH 7.0±0.1 with sodium hydroxide. The obtained PTX-BCL NPs were stored at 2°C–8°C.


Delivery of baicalein and paclitaxel using self-assembled nanoparticles: synergistic antitumor effect in vitro and in vivo.

Wang W, Xi M, Duan X, Wang Y, Kong F - Int J Nanomedicine (2015)

Transmission electron microscopy imaging of (A) paclitaxel (PTX) nanoparticles (NPs), (B) baicalein (BCL) NPs, and (C) PTX-BCL NPs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4447173&req=5

f3-ijn-10-3737: Transmission electron microscopy imaging of (A) paclitaxel (PTX) nanoparticles (NPs), (B) baicalein (BCL) NPs, and (C) PTX-BCL NPs.
Mentions: PTX-BCL NPs were prepared by the nanoprecipitation method.51 The amphiphilic nature of FA-V-PTX and HA-L-BCL makes it possible for them to self-assemble into NPs with PTX and BCL as the inner core, FA and HA as the hydrophilic shell (Figure 3). Briefly, PLGA (50 mg)-acetone (3 mL) solution was prepared. FA-V-PTX and HA-L-BCL (1/5 and 1/2, wPTX/wBCL) were dissolved in acetone–water solution (50:50, w/w). Then, PLGA, FA-V-PTX, and HA-L-BCL solution were simultaneously and separately added dropwise into the 0.05% poloxamer 188 containing aqueous solution. The mixture was stirred at 600 rpm at RT until complete evaporation of the organic solvent occurred. The redundant stabilizers were removed by centrifugation at 1,000 × g and 4°C for 30 minutes. The pellet was vortexed and resuspended in Milli-Q® water, washed several times, filtered through a 0.45 μm membrane, and adjusted to pH 7.0±0.1 with sodium hydroxide. The obtained PTX-BCL NPs were stored at 2°C–8°C.

Bottom Line: Combination anticancer therapy is promising to generate synergistic anticancer effects to maximize the treatment effect and overcome multidrug resistance.The PTX-BCL NPs displayed remarkably better antitumor activity over a wide range of drug concentrations, and showed an obvious synergism effect with CI50 values of 0.707 and 0.513, indicating that double-ligand modification and the co-delivery of PTX and BCL prodrugs with self-assembled NPs had remarkable superiority over other formulations.Enhanced synergistic anticancer effects were achieved by PTX-BCL NPs, and multidrug resistance of PTX was overcome by this promising targeted nanomedicine.

View Article: PubMed Central - PubMed

Affiliation: Department of Chinese Medicine Integrated Traditional Chinese Medicine and Western Medicine, General Hospital of Ji'nan Command, People's Liberation Army, Ji'nan, People's Republic of China.

ABSTRACT

Purpose: Combination anticancer therapy is promising to generate synergistic anticancer effects to maximize the treatment effect and overcome multidrug resistance. The aim of the study reported here was to develop multifunctional, dual-ligand, modified, self-assembled nanoparticles (NPs) for the combination delivery of baicalein (BCL) and paclitaxel (PTX) prodrugs.

Methods: Prodrug of PTX and prodrug of BCL, containing dual-targeted ligands of folate (FA) and hyaluronic acid (HA), were synthesized. Multifunctional self-assembled NPs for combination delivery of PTX prodrug and BCL prodrug (PTX-BCL) were prepared and the synergistic antitumor effect was evaluated in vitro and in vivo. The in vitro transfection efficiency of the novel modified vectors was evaluated in human lung cancer A549 cells and drug-resistant lung cancer A549/PTX cells. The in vivo antitumor efficiency and systemic toxicity of different formulations were further investigated in mice bearing A549/PTX drug-resistant human lung cancer xenografts.

Results: The size of the PTX-BCL NPs was approximately 90 nm, with a positive zeta potential of +3.3. The PTX-BCL NPs displayed remarkably better antitumor activity over a wide range of drug concentrations, and showed an obvious synergism effect with CI50 values of 0.707 and 0.513, indicating that double-ligand modification and the co-delivery of PTX and BCL prodrugs with self-assembled NPs had remarkable superiority over other formulations.

Conclusion: The prepared PTX-BCL NP drug-delivery system was proven efficient by its targeting of drug-resistant human lung cancer cells and delivering of BCL and PTX prodrugs. Enhanced synergistic anticancer effects were achieved by PTX-BCL NPs, and multidrug resistance of PTX was overcome by this promising targeted nanomedicine.

No MeSH data available.


Related in: MedlinePlus