title: Formulation and evaluation of tacrolimus-loaded galactosylated Poly(lactic-co-glycolic acid) nanoparticles for liver targeting.
abstract: OBJECTIVE
  The aim of this investigation was to formulate liver targeted tacrolimus-loaded nanoparticles for reducing renal distribution and thereby decreasing nephrotoxicity.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Galactosylated PLGA nanoparticles seem to be a promising carrier for liver targeting of tacrolimus.
authors.affiliation: Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
authors.forename: Nishita P
authors.initials: NP
authors.lastname: Mistry
authors.affiliation: Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
authors.forename: Jagruti L
authors.initials: JL
authors.lastname: Desai
authors.affiliation: Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
authors.forename: Hetal P
authors.initials: HP
authors.lastname: Thakkar
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D005690:Galactose / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016559:Tacrolimus; D005690:Galactose
keywords: asialoglycoprotein receptors; conjugation; galactose; liver targeting; poly (lactide-co-glycolic acid)