Injectable actarit-loaded solid lipid nanoparticles as passive targeting therapeutic agents for rheumatoid arthritis

Int J Pharm. 2008 Mar 20;352(1-2):273-9. doi: 10.1016/j.ijpharm.2007.10.014. Epub 2007 Oct 22.


This work systematically studied the intravenous injection formulation of solid lipid nanoparticles (SLNs) loaded with actarit, a poor water soluble anti-rheumatic drug. The goal of this study was to design passive targeting nanoparticles which could improve therapeutic efficacy and reduce side-effects such as nephrotoxicity and gastrointestinal disorders commonly associated with oral formulations of actarit. Based on the optimized results of single-factor and orthogonal design, actarit-loaded SLNs were prepared by a modified solvent diffusion-evaporation method. The formulated SLNs were found to be relatively uniform in size (241+/-23 nm) with a negative zeta potential (-17.14+/-1.6 mV). The average drug entrapment efficiency and loading were (50.87+/-0.25)% and (8.48+/-0.14)%, respectively. The actarit-loaded SLNs exhibited a longer mean retention time in vivo (t(1/2(beta)), 9.373 h; MRT, 13.53 h) compared with the actarit 50% propylene glycol solution (t(1/2(ke)), 0.917 h; MRT, 1.323 h) after intravenous injection to New Zealand rabbits. The area under curve of plasma concentration-time (AUC) of actarit-loaded SLNs was 1.88 times greater than that of the actarit in 50% propylene glycol solution. The overall targeting efficiency (TE(C)) of the actarit-loaded SLNs was enhanced from 6.31% to 16.29% in spleen while the renal distribution of actarit was significantly reduced as compared to that of the actarit solution after intravenous administration to mice. These results indicated that injectable actarit-loaded solid lipid nanoparticles were promising passive targeting therapeutic agents for rheumatoid arthritis.

MeSH terms

  • Animals
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / chemistry
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / toxicity
  • Area Under Curve
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Drug Carriers*
  • Drug Compounding
  • Female
  • Injections, Intravenous
  • Kidney / metabolism
  • Lipids / chemistry*
  • Male
  • Mice
  • Nanoparticles*
  • Particle Size
  • Phenylacetates / administration & dosage*
  • Phenylacetates / chemistry
  • Phenylacetates / pharmacokinetics
  • Phenylacetates / toxicity
  • Rabbits
  • Solubility
  • Spleen / metabolism
  • Technology, Pharmaceutical / methods
  • Tissue Distribution


  • Antirheumatic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Lipids
  • Phenylacetates
  • 4-(acetylamino)benzeneacetic acid