Formulation and evaluation of tacrolimus-loaded galactosylated Poly(lactic-co-glycolic acid) nanoparticles for liver targeting.

OBJECTIVE: The aim of this investigation was to formulate liver targeted tacrolimus-loaded nanoparticles for reducing renal distribution and thereby decreasing nephrotoxicity. METHOD: Poly lactic-co-glycolic acid (PLGA) was galactosylated, and confirmation of galactosylation was performed by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. Tacrolimus-loaded PLGA nanoparticles (Tac-PLGA NP) and galactosylated PLGA nanoparticles (Tac-Gal-PLGA NPs) were prepared by ultrasonic emulsification solvent evaporation technique and characterized. KEY FINDINGS: The size of both the formulations was below 150 nm and negative zeta potential indicated the stability and reticuloendothelial system targeting efficiency. The in-vitro release and pharmacokinetics showed sustained release of tacrolimus from nanoparticles in comparison to plain drug solution. The biodistribution studies revealed the potential of both the nanoparticulate systems to target tacrolimus to the liver for prolonged periods of time compared with the plain drug solution. However, significantly higher liver and spleen targeting efficiency of Tac-Gal-PLGA NPs compared with Tac-PLGA NPs was evident indicating its active targeting. Significantly lower distribution in the kidney from nanoparticles indicated the possibility of reduced nephrotoxicity - the principal reason for patient non-compliance. Both nanoparticles showed stability at refrigerated condition (5°C ± 3°C) upon storage for 1 month. CONCLUSION: Galactosylated PLGA nanoparticles seem to be a promising carrier for liver targeting of tacrolimus.

Gemcitabine hydrochloride-loaded functionalised carbon nanotubes as potential carriers for tumour targeting.

The objective of the present work was to formulate gemcitabine hydrochloride loaded functionalised carbon nanotubes to achieve tumour targeted drug release and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000 was taken for loading of gemcitabine hydrochloride. The formulation was evaluated for different parameters. The results showed that maximum drug loading efficiency achieved was 41.59% with an average particle size of 188.7 nm and zeta potential of -10-1 mV. Scanning electron microscopy and transmission electron microscopy images confirmed the tubular structure of the formulation. The carbon nanotubes were able to release gemcitabine hydrochloride faster in acidic pH than at neutral pH indicating its potential for tumour targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern. Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride. Stability studies indicated that lyophilised samples of the formulation were more stable for 3 months under refrigerated condition than at room temperature. Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride.