Marked hypotensive and blood flow-increasing effects of a new lipo-PGE(1) (lipo-AS013) due to vascular wall targeting

Lipo-AS013 is being developed as an improved formulation of lipo-PGE,. whic h is widely used in clinical practice in Japan and some Asian countries. We have previously reported that lipo-AS013. which is a lipid microsphere (LM ) preparation of a chemically stable and lipophilic PGE, prodrug (AS013. Fi g. I). slowly releases small amounts of the active ingredient (AS013) in hu man plasma. In the present study. to estimate the vascular wall targeting a bility and efficacy of lipo-AS013. we determined the hypotensive and blood Row-increasing effects of lipo-AS013. lipo-PGE(1). PGE(1)CD. and AS013. Lip o-AS013 was found to have longer-lasting hypotensive and blood Row-increasi ng effects than the other agents. The two LM preparations, lipo-PGE(1) and lipo-AS013, had a markedly stronger effect than PGE(1)CD and AS013 alone. d emonstrating the benefit of drug delivery using LM. In spontaneously hypert ensive rats (SHR). lipo-AS013 also had a significant hypotensive effect. To confirm vascular wall targeting by lipo-AS013. the localization of Pt;E, i n the aorta and neovascular capillaries of rat was investigated by immunost aining. The results indicated that lipo-AS013 was more efficient at deliver ing the active ingredient (AS013) to the vessel wall. In conclusion, lipo-A S013 could supersede lipo-PGE, and PGE,CD in clinical use. (C) 2001 Elsevie r Science B.V. All rights reserved.