Designing of fucosylated dendrimers as a biocompatible carrier for the targeted delivery of chrysin to human lung cancer cells

Dendrimers, a polymeric macromolecule, have been explored for improving the solubility of water-insoluble drugs, and PAMAM is the most explored dendrimer in nanomedicine. But amine-terminated PAMAM dendrimers confer toxicity to healthy cells. Chrysin (CRY) is a plant-derived phenolic component with anticancer properties and has emerged as a safer drug for the treatment of various cancers, including lung cancer. However, its limited aqueous solubility and poor in vivo stability are the major hurdles to its development as a potential anticancer molecule. In the present work, generation 4 PAMAM dendrimers were functionalized with fucose to overcome the toxicity of dendrimers, enhance the aqueous solubility of CRY, and improve drug targeting to cancer cells. The prepared CRY-loaded fucosylated PAMAM dendrimers (CRY-FUC-PAMAM) were found to have high aqueous solubility and sustained drug release. In the in-vitro studies, CRY-FUC-PAMAM showed improved cytotoxicity with a lower IC50 value at both 24 h and 48 h (1.8 μg/mL and 0.7 μg/mL, respectively), resulting from increased apoptosis and cellular uptake of FUC-PAMAM in A549 human lung cancer cells in comparison to free CRY, whereas FUC-PAMAM was found to be non-toxic. Overall, this biocompatible fucosylated dendrimer could be used as a nanocarrier for the delivery of CRY as a targeted nanomedicine for lung cancer. [Display omitted] •Chrysin loaded fucosylated dendrimers (CRY-FUC-PAMAM) formulation was prepared and characterized.•The physicochemical properties of chrysin were improved with fucosylated dendrimers.•Fucosylated PAMAM was biocompatible and targeted the glycan receptors overexpressed in lung cancer cells.•CRY-FUC-PAMAM caused induction of apoptosis, increased cytotoxicity, and inhibition of colony formation.