Biocompatible Dendrimer for Anti Cancer Therapy Synthesis Characterization and Evaluation

Abstract

As estimated by World Health Organization (WHO), cancer is one of the fatal diseases worldwide. Certain nanotechnology-driven formulations provide efficacious and safe anticancer treatment using small molecule drugs. Dendrimers being a versatile polymer-based nanoplatform, biocompatible and biodegradable dendrimers can maximize the therapeutic value of already approved pharmaceuticals. Due to L-glutamic acid monomer unit, poly(L-glutamic acid) dendrimers appear to be biocompatible and biodegradable. Like amino acid based nanomaterials, biological lipid-based nanomaterials are preferred due to their capacity to enhance cell permeability of drugs. Hence, a hybrid dendritic lipopeptide nanocarrier was explored for drug delivery application of a model anticancer drug gefitinib in the present work. newlinePoly(L-glutamic acid) dendrimers were synthesized through simple and rapid solution phase synthesis using amide coupling agents. Three 2.5 generation peptide dendrimers were synthesized using L-glutamic acid as dendron forming monomer units with myristoyl group at the core. As the synthesized dendrimers differed in peripheral functional groups (benzyl, carboxyl and hydroxyl) their physicochemical properties were significantly different. Dendrimer with benzyl periphery demonstrated nanoparticle forming potential and was found to be biocompatible in in vitro cytocompatibility and in vivo acute toxicity studies. Hence, it was selected for further pharmaceutical evaluation over dendrimers with carboxyl and hydroxyl groups demonstrating surfactant like properties. newlineThe formulation potential of synthesized pharmaceutical excipient was tested with model anticancer tyrosine kinase inhibitor drug gefitinib. Using solvent evaporation-probe ultrasonication method, gefitinib was loaded in synthesized excipient matrix. The formulation was optimized by implementing Box-Behnken design of Design of Experiments.