Long-circulating delivery of bioactive polysaccharide from radix ophiopogonis by PEGylation.

Background: Radix ophiopogonis polysaccharide (ROP) has been found to be effective against myocardial ischemia. One of main problems with its use is its short in-vivo half-life, which makes the development of an effective delivery system necessary. To achieve better therapeutic effects and patient compliance by prolonging its retention in plasma and increasing its distribution in targets, ROP was PEGylated (PEG, polyethylene glycol) in this study.

Methods: Through a moderate coupling reaction between hydroxyl-activated ROP and amino-terminated methoxy-PEG (mPEG) (30 or 40 kDa), together with a greater than 1 molar ratio of ROP to mPEG in reaction, long-circulating and potentially bioactive PEGylated ROPs, with PEG grafting number of ~1.0, were prepared, characterized, and the pharmacokinetics evaluated.

Results: Relative to ROP, whose half-life was approximately 0.7 hours, the two conjugates prepared, following intravenous administration, showed markedly prolonged retention in systemic circulation with half-lives in blood of 78.4 and 88.3 hours, respectively. When given subcutaneously, their in-vivo mean residence times were further markedly prolonged by the slow absorption phase. They were found to be well absorbed after subcutaneous administration, with absolute bioavailability being 75.4% and 43.9%, respectively.

Conclusion: With apparent molecular masses not exceeding 43 kDa, the conjugates prepared have been and will be demonstrated to have prominent advantages for ROP delivery, such as: the good absorption following subcutaneous, intramuscular, or other ways of administration; the effective utilization of the enhanced permeability and retention effect caused by ischemia; and the rapid diffusion within target tissues.