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.
Gao
Yu
Y
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Xu
Pengfei
P
Chen
Lingli
L
Li
Yaping
Y
D000527:Alprostadil / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D054709:Lecithins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D011817:Rabbits; D051381:Rats; D013025:Glycine max / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D054709:Lecithins; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000527:Alprostadil