Pharmacokinetic Properties and Applications as Drug Carriers

Early reports showed that the anti-cancer drug, doxorubicin, could be incorporated into a PEG-polyaspartate block copolymer.29,30 PEG constituted the outer shell of the micelle that conferred a stealth property on the drug. After intravenous injection, doxorubicin incorporated in polymeric micelles was less avidly taken up by the reticuloendothelial system (RES) and could be retained in the circulation for a longer time compared with an intravenous injection of doxorubicin alone.29 The in vivo anti-tumor activity against Colon-26 solid tumors showed that there was critical suppression of tumor growth and a prolonged life span for doxorubicin incorporated in polymeric micelles when administered to mice.30

Another type of polymeric micelle composed poly(ethylene oxide-aspartate)block copolymer and doxorubicin conjugate also exhibited a sustained circulation in blood,31 reduced uptake by the RES, and more than 100 times higher accumulation in tumors in Colon-26 tumor-bearing mice.32 Another report described the tumor-targeting delivery of paclitaxel by block copolymers producing both anti-tumor activity and a reduction in a major side effect of paclitaxel, neurotoxicity.33

In a previous study, all-trans retinoic acid (ATRA) incorporated polymeric micelles produced a higher AUC and lower hepatic clearance than free ATRA, demonstrating escape from the RES.34 Polymeric micelles have also been used in an active targeting approach, using the fact that certain pathological processes are associated with local temperature increase and/or acidosis. The use of polymeric micelles prepared from thermo-35,36 or pH-sensitive37 block co-polymers allows the disintegration of micelles and release of the incorporated drugs specifically at the site of interest. Additionally, the micelles can be targeted by attaching to their surface a vector molecule such as an antibody, peptide, lectin, saccharide, hormone, or some low-molecular weight compounds if this vector molecule binds to ligands characteristic of the site of interest.

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