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

Abstract

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.

• Authors: Jiesheng Ye, Qun Wang, Xuefeng Zhou, Na Zhang
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 352 Issue 1-2 Pg. 273-9 (Mar 20 2008) ISSN: 0378-5173 [Print] Netherlands
• PMID: 18054182 (Publication Type: Journal Article)

Chemical References

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

Topics

• Animals
• Antirheumatic Agents (administration & dosage, chemistry, pharmacokinetics, 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, chemistry, pharmacokinetics, toxicity)
• Rabbits
• Solubility
• Spleen (metabolism)
• Technology, Pharmaceutical (methods)
• Tissue Distribution