Background:
Improving the aggregation and penetration in tumor sites increases the anti-tumor efficacy of nanomedicine. In the current study, we designed cyclodextrin modified PLGA nanoparticles loaded with paclitaxel to elevate the accumulation and prolong circulation of chemotherapy drugs
in vivo
.
Methods:
The PLGA nanoparticles loaded with paclitaxel (PTX PLGA NPs) and cyclodextrin (CD) modified PLGA nanoparticles loaded with paclitaxel (PTX PLGA/CD NPs) were prepared using the emulsification solvent evaporation method. The nanoparticles were characterized by particle size, zeta potential, encapsulation efficiency, infrared spectroscopy analysis and X-Ray diffraction (XRD). Then, drug release of the nanoparticles was evaluated via reverse dialysis method
in vitro
. Finally, the
in vivo
distribution fate and pharmacokinetic characteristics of the nanoparticles were assessed in mice and rats.
Results:
The average particle size, zeta potential, and encapsulation efficiency of PTX PLGA NPs were (163.57±2.07) nm, - (20.53±2.79) mV and (60.44±6.80)%. The average particle size, zeta potential, and encapsulation efficiency of PTX PLGA/CD NPs were (148.57±1.66) nm, - (11.42±0.84) mV and (85.70±2.06)%.
In vitro
release studies showed that PTX PLGA/CD NPs were released more slowly compared to PTX PLGA NPs under normal blood pH conditions, while PTX PLGA/CD NPs were released more completely under tumor site pH conditions. The modified PLGA nanocarrier (PLGA/CD NPs) increased drug residence time and accumulation than the plain PLGA nanocarrier (PLGA NPs)
in vivo
distribution. In addition, the elimination half-life, area under the drug-time curve, and maximum blood concentration of the nanoparticle group were higher than those of Taxol
®
, especially the PTX PLGA/CD NPs group, which was significantly different from Taxol
®
and plain nanoparticle groups (
p
<0.001).
Conclusions:
The 2-HP-β-CD modified PLGA nanoparticles prolonged circulation time and accumulation of the chemotherapy drug paclitaxel
in vivo
.