Prostaglandin E1 encapsulated into lipid nanoparticles improves its anti-inflammatory effect with low side-effect.

Prostaglandin E(1) (PGE1) shows various pharmacological activities including anti-inflammation. However, the rapid metabolization and inactivation of the intravenously administered PGE1 during the first passage through the lungs result in significant non-compliance in clinical trials which greatly limits its application. The aim of this work was to prepare the lipid nanoparticles loading PGE1 to improve its anti-inflammatory effect with low side-effect. The experimental results showed that PGE1 loaded lipid nanoparticles (PLNs) could be successfully prepared by high pressure homogenization with particle size 68.1+/-4.7 nm, zeta potential -3.32+/-0.37 mV and entrapment efficiency 92.1+/-1.3%. PLNs exhibited a sustained release with low burst drug release. PLNs could improve the inhibition effects of PGE1 on lipopolysaccharides (LPS)-induced TNF-alpha expression on macrophage RAW264.7 cells, and improve the inhibition of lymphocyte to endothelial cell adhesion and ICAM-1 adhesion molecule expression on HUVEC and MDA-MB-468 cell membrane. No allergenicity, vascular and muscle irritation were induced in animals by PLNs even at double of the highest drug concentration of clinical infusion. As a result, PLNs could be a more potential delivery system for PGE1 in the treatment of inflammation-related diseases. 2009 Elsevier B.V. All rights reserved.