Synthesis of a Smart Nanovehicle for Targeting Liver
A protocol for the synthesis of a smart drug delivery system based on gold nanoparticles has been described in this chapter. The synthesized drug delivery system has been shown to release the bioactive material in response to an intracellular stimulus (glutathione concentration gradient) and hence shown to behave in an intelligent manner. Gold nanoparticles have been employed as the core material with the surface functionalities of thiolated PEG. PEG owing to its non-immunogenicity and non-antigenicity would impart considerable stability and longer in vivo circulation time to the gold nanoparticles. The end groups of PEG chains have been derivatized with functional groups like aldehyde (–CHO) and amine (–NH2) which could behave as flexible arms for the attachment of “target specific ligands” and other bioactive substances. Lactose, a liver targeting ligand, has been employed as the target specific moiety. A Coumarin derivative has been synthesized and used as the model fluorescent tag as well as a linker to examine the glutathione-mediated release through fluorescence spectroscopy and for the conjugation of bioactive molecules, respectively. A check for the cytocompatibility of the synthesized nanovehicle on the cultured mammalian cell lines has also been carried out. Finally, in the latter parts of the chapter (mimicking the in vivo conditions), time-dependent in vitro release of the model fluorescent moiety has also been analyzed at different glutathione concentrations.
Key wordsSmart drug delivery system Targeting liver Gold nanoparticles Thiolated PEG Lactose Coumarin Glutathione Fluorescence spectroscopy
The authors thank the Department of Science and Technology (DST), New Delhi for the financial assistance in the form of Junior Research Fellowship and the University Science Instrumentation Centre, University of Delhi, for providing the characterization facilities. The authors also thank Dr. Y. Singh (Scientist “G”, IGIB, Delhi) for carrying out the cytotoxicity work in his lab.
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