Injectable actarit-loaded solid lipid nanoparticles as passive targeting therapeutic agents for rheumatoid arthritis.
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.
The School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Ji'nan, Shandong Province, China.
Jiesheng
J
Ye
Qun
Q
Wang
Xuefeng
X
Zhou
Na
N
Zhang
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D010648:Phenylacetates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D011817:Rabbits; D012995:Solubility; D013154:Spleen / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution
D018501:Antirheumatic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D010648:Phenylacetates; C052562:4-(acetylamino)benzeneacetic acid