Le, silver nanoparticles coated with poly(vinyl)pyrrolidone have been discovered to become efficient against unique HIV-strains [16]. Aptamer-conjugated gold nanoparticles were also exploited as productive inhibitors of viral enzymes [17]. We’ve got previously described the usefulness of carbohydratecoated gold nanoparticles (GNPs) as a carrier for unique structures related to HIV envelope [18]. GNPs coated with oligomannosides with the gp120 (manno-GNPs) were in a position to inhibit the DC-SIGN-mediated HIV-1 trans-infection of human T-cells [19] and gold glyconanoparticles coated with sulfated ligands showed to interfere with the adhesion/fusion of HIV throughout its entry [20]. Our methodology for preparing GNPs allows the construction of particles simultaneously containing carbohydrates, peptides and targeting molecules within a controled way [21]. The use of biocompatible gold glyconanoparticles as scaffolds for the antiviral drugs could bring some important benefits including the improvement with the solubility in water and biological media with the drugs and also the improvement of cellular uptake because of the presence of carbohydrates around the GNPs. In addition a nearby boost in the drug concentration on the gold surface could also strengthen their antiviral activity. We reasoned that the presence of various antiretroviral molecules on carbohydrate-coated gold nanoparticles could cause a drug-delivery technique and/or microbicides in a position to inhibit viral replication or to stop sexual infection. We’ve got previously demonstrated that glucose-coated gold nanoparticles are water-soluble and noncytotoxic to various cell lines in the tested concentrations [22]. Glucose-coated nanomaterials have already been proposed as good intracellular delivery tool plus the internalization and uptake of glucose-coated nanoparticles have already been described on unique cell lines [23-26]. Additionally glucose-coated gold nanoparticles didn’t elicit any immune response in animal models [27,28]. We therefore decided to make use of them as a scaffold to insert antiretroviral drugs to construct new multivalent anti-HIV systems. Here we describe the preparation of anti-HIV prodrug candidates and their assembly on three nm glucose-coated gold nanoparticles as a BCRP site potential drug-delivery system. As antiviral drugs, the nucleoside analog reverse transcriptase inhibitorsBeilstein J. Org. Chem. 2014, ten, 1339346.(NRTIs) abacavir (ABC) and lamivudine (3TC) were selected. NRTIs are drugs that compete inside the cytoplasm as triphosphates with endogenous nucleoside substrates acting as chain terminators inside the DNA polymerisation reaction catalyzed by HIV-1 RT [3]. Each drugs have been transformed in ester derivatives to prepare the GNPs. The pH-mediated GABA Receptor Compound release from the drugs from the GNPs surface was evaluated and cellular experiments demonstrated that abacavir and lamivudine ester derivatives tailored onto the gold gluconanoparticles have an antiviral activity equivalent to the cost-free drugs.Results and DiscussionPreparation of anti-HIV prodrug-GNPsAs a proof-of-principle to get a additional exploration of gold glyconanoparticles as drug-delivery system, we ready glucosecoated gold nanoparticles and functionalized them with in clinical use antiviral drugs abacavir (ABC) and lamivudine (3TC). The drugs have been functionalized in the primary hydroxy groups with 11-mercaptoundecanoic acid to obtain the prodrug candi-date with a simple hydrolysable ester group that allows the release in the drug in the GNPs by enzymatic or pH mediated hydrolysis. 11-Mercaptou.
