Maxitarg-A Novel Targeting Approach For Hepatic Cancer

摘要

"MAXITARG" is a novel drug delivery approach to maximize drug accumulation in hepatocellular carcinoma cells. Maxitarg relies on a novel targeting agent (NTA) with high affinity for asialoglycoprotein receptors, which are over expressed in the liver carcinoma cells. The present study reports application of Maxitarg in the design of a targeted nanoparticulate drug delivery system (DDS) of doxorubicin with the specific objective of enhancing liver uptake and decreasing dose related cardiotoxicity of the drug. Alginic acid - sodium alginate nanoparticles (NP) loaded with doxorubicin and NTA were prepared by controlled gelation method using novel stabilizing agent Eudragit E100. Encapsulation efficiency (EE) of > 95% reflected minimum drug loss during processing. Average particle size of optimized nanoparticles (NP) ranged between 200-550 nm. NP's showed sustained in vitro drug release over a period of 60 hrs in pH 7.4 buffer at 37℃. Biodistribution study of NP revealed rapid and maximal uptake in the liver with significant drug accumulation up to 24 hrs, moreover low concentration of doxorubicin was evident in kidney, spleen and lung while negligible drug concentration was detected in heart up to 24 hrs. Plain doxorubicin however revealed high drug concentration in the heart at 1 hr detectable up to 24 hrs, moreover uptake by the liver was very low. Other tissues like lung, kidney, and spleen also showed presence of drug.