Nanoformulation of Paclitaxel: Exploring the Cyclodextrin / PLGA Nano Delivery Carrier to Slow Down Paclitaxel Release, Enhance Accumulation in Vivo

Abstract

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 .