Development and characterization of hyaluronic acid-anchored PLGA nanoparticulate carriers of doxorubicin

摘要

A novel hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide)(HA-PEG-PLGA)copo-lymer was synthesized and characterized by infrared and nuclear magnetic resonance spectroscopy.The nanoparticles of doxorubicin(DOX)-loaded HA-PEG-PLGA were prepared and compared with monomethoxy(polyethylene glycol)(MPEG)-PLGA nanoparticles.Nanoparticles were prepared using drug-to-polymer ratios of 1:1 to 1:3.Drug-to-polymer ratio of 1:1 is considered the optimum formulation on the basis of low particle size and high entrapment efficiency.The optimized nanoparticles were characterized for morphology,particle size measurements,differential scanning calorimetry,x-ray diffractometer measurement,drug content,hemolytic toxicity,subacute toxicity,and in vitro DOX release.The in vitro DOX release study was performed at pH 7.4 using a dialysis membrane.HA-PEG-PLGA nanoparticles were able to sustain the release for up to 15 days.The tissue distribution studies were performed with DOX-loaded HA-PEG-PLGA and MPEG-PLGA nanoparticles after intravenous(TV)injection in Ehrlich ascites tumor-bearing mice.The tissue distribution studies showed a higher concentration of DOX in the tumor as compared with MPEG-PLGA nanoparticles.The in vivo tumor inhibition study was also performed after IV injection of DOX-loaded HA-PEG-PLGA nanoparticles up to 15 days.DOX-loaded HA-PEG-PLGA nanoparticles were able to deliver a higher amount of DOX as compared with MPEG-PLGA nanoparticles.The DOX-loaded HA-PEG-PLGA nanoparticles reduced tumor volume significantly as compared with MPEG-PLGA nanoparticles.