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 (P_20k-R), 40-kDa PEG mono-modified ROP (P_40k-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 P_40k-R. With regard to P_20k-R, both its targeting efficacy and its level in infarcted myocardium at 3 hours postdose were comparable to P_40k-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