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.
- MeSH
- asialoglykoproteinový receptor metabolismus MeSH
- buňky Hep G2 MeSH
- cholesterol chemie MeSH
- doxorubicin aplikace a dávkování chemie metabolismus MeSH
- farmaceutická chemie metody MeSH
- galaktany chemie MeSH
- hepatocelulární karcinom farmakoterapie metabolismus MeSH
- játra účinky léků metabolismus MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- liposomy chemie MeSH
- nádorové buněčné linie MeSH
- nádory jater farmakoterapie metabolismus MeSH
- polyethylenglykoly chemie MeSH
- protinádorové látky aplikace a dávkování chemie metabolismus MeSH
- tkáňová distribuce MeSH
- velikost částic MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
