We have developed active targeting liposomes to deliver anticancer agents to ASGPR which will contribute to effective treatment of hepatocellular carcinoma. Active targeting is achieved through polymeric ligands on the liposome surface. The liposomes were prepared using reverse phase evaporation method and doxorubicin hydrocholoride, a model drug, was loaded using the ammonium sulphate gradient method. Liposomes loaded with DOX were found to have a particle size of 200nm with more than 90% entrapment efficiency. Systems were observed to release the drug in a sustained manner in acidic pH in vitro. Liposomes containing targeting ligands possessed greater and selective toxicity to ASGPR positive HepG2 cell lines due to specific ligand receptor interaction. Bio-distribution studies revealed that liposomes were concentrated in the liver even after 3h of administration, thus providing conclusive evidence of targeting potential for formulated nanosystems. Tumor regression studies indicated greater tumor suppression with targeted liposomes thereby establishing superiority of the liposomal system. In this work, we used a novel methodology to guide the determination of the optimal composition of the targeting liposomes: molecular dynamics (MD) simulation that aided our understanding of the behaviour of the ligand within the bilayer. This can be seen as a demonstration of the utility of this methodology as a rational design tool for active targeting liposome formulation.

Academy of the Sciences of the Czech Republic Prague Czech Republic; Centre for Drug Research Division of Pharmaceutical Bioscience Faculty of Pharmacy University of Helsinki FI 00014 Helsinki Finland

Bombay College of Pharmacy University of Mumbai Mumbai 400098 India

Center for Electron Microscopy of the Medical Faculty Friedrich Schiller University Jena Ziegelmühlenweg 1 D 07740 Jena Germany

Centre for Drug Research Division of Pharmaceutical Bioscience Faculty of Pharmacy University of Helsinki FI 00014 Helsinki Finland

Council of Scientific and Industrial Research Centre for Cellular and Molecular Biology Hyderabad 500007 India

Department of Pharmaceutical Technology Friedrich Schiller University Jena Lessing str 8 D 07743 Jena Germany

Department of Physics Tampere University of Technology PO Box 692 FI 33101 Tampere Finland

Small Animal Imaging Facility Kharghar Mumbai 410210 India

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