Targeting delivery of Radix Ophiopogonis polysaccharide to ischemic/reperfused rat myocardium by long-circulating macromolecular and liposomal carriers

Abstract

LiNa Wang,1,2,* ChunXia Yao,1,* Fei Wu,2 Xiao Lin,1,2 Lan Shen,1 Yi Feng2 1College of Chinese Materia Medica, 2Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Drug delivery to ischemic myocardium is an enormous challenge. This work aimed to characterize cardiac delivery behaviors of mono-polyethylene glycosylated (PEGylated) conjugates and long-circulating liposomes (L-Lps) with Radix Ophiopogonis polysaccharide (ROP) as drug. The results showed that compared to native ROP, 32-, 52-, and 45-fold increases in blood half-life were achieved by 20-kDa PEG mono-modified ROP (P20k-R), 40-kDa PEG mono-modified ROP (P40k-R), and ROP-loaded L-Lp, respectively. With comparable blood pharmacokinetics, ROP-loaded L-Lp showed both significantly higher targeting efficacy and drug exposure in infarcted myocardium than P40k-R. With regard to P20k-R, both its targeting efficacy and its level in infarcted myocardium at 3 hours postdose were comparable to P40k-R, but its level in blood and myocardium reduced obviously faster. As a whole, the results indicate that both loading in L-Lps and mono-PEGylation are effective in targeting drug to ischemic myocardium, but the former appears to induce stronger effects. Keywords: PEGylation, liposome, myocardial targeting, Radix Ophiopogonis polysaccharide, fluorescent imaging