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Lentinan (LNT for short), extracted and purified from one kind of edible mushrooms, Lentinus edodes, is a high molecular weight glucan. As a kind of biological response modifiers, LNT has displayed various kinds of immune activities and played important role in prevention and treatment of various chronic diseases. However, LNT injection used clinically nowadays has the deficiency of short half-time, which limited its application. Liposomes have the potentiality of protecting their encapsulated drug from the external environment to act as sustained release depots, increasing efficacy and therapeutic index of drug, and altering the pharmacokinetic and pharmacodynamic property of drugs. For the reasons mentioned above, liposome was chosen as LNT carrier with a view to prolong the retention time in vivo and enhance the therapeutic effect.Based on preliminary study, the pharmacokinetics and tissue distribution of both LNT liposome and LNT injection were studied and compared to reveal the the dynamic process of LNT in vivo, access to pharmacokinetic parameters, clarify the characteristics of drug distribution, evaluate the of preparation quality, and provid information for pre-clinical research .Tachypleus Amebocyte Lysate (TAL for short) was used to detect LNT quantitatively and applied on the pharmacokinetics and tissue distribution study of LNT liposome in rats. After intraperitoneal injection of 0.2mg·kg-1 LNT injection and LNT liposome to rats respectively, serum and tissue (heart, liver, spleen, lung, and kidney) samples were collected and detected. The pharmacokinetic parameters were calculated by DAS software and the distribution character were evalued by targeting parameters. Compared with LNT solution, the LNT liposome did not significantly change the half-life, peak concentration, clearance and AUC while it increased the drug targeting to liver and lung.Since the result of pharmacokinetic study in rats is different from previous pharmacokinetic study in dogs, we selected intravenous drug delivery in mice to verify the experimental results in order to avoid the impact of administration mode. Mice were subjected to intravenous injection of 0.5mg·kg-1 LNT injection and LNT liposome respectively and sacrificed after certain time to collected samples for detection.The result showed that, compared with LNT injection, the LNT liposome had no significant difference on pharmacokinetics character; however, it changed the tissue distribution by increasing the drug concentration and prolonged the retention time in liver, spleen and lung.Through the verification of two animals and two delivery method, we concluded that LNT liposome did not alter the pharmacokinetics of drugs, but influenced the tissue distribution by modifying the targeting and sustained-release effect of LNT.
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