The synthesis of functionalized graphene oxide by polyester dendrimer as a pH-sensitive nanocarrier for targeted delivery of venlafaxine hydrochloride: Central composite design optimization

Abstract

In this study, a new type of polyester dendrimer was synthesized through direct esterification reaction between phloroglucinol (PG) and terephthalic acid (TPA) in the presence of a catalyst. Graphene oxide (GO) functionalized with polyester dendrimer, decorated with 3,4-dihydroxybenzoic acid (DHB), was used to sustain delivery of venlafaxine hydrochloride (VH) as an antidepressant drug. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Brunauer–Emmett–Teller (BET), and thermogravimetric analysis (TGA) confirmed the attachment of polyester dendrimer onto the GO. Different variables, including pH, contact time, and temperature were optimized to evaluate the adsorption of VH on the PAH-GO/PGTPA/DHB Dendr using a central composite design (CCD). The highest adsorption percentage was obtained at pH of 7, contact time of 20 min, and temperature of 30 °C. The sorption mechanism was determined via the Langmuir isotherm model (R2 = 0.9965), representing the monolayer adsorption with the adsorption capacity of 19.72 mg g−1. PAH-GO/PGTPA/DHB Dendr displayed a fast sorption rate, and the pseudo-second-order kinetic model confirmed the best correlation between experimental data with R2 = 0.9995. The release of the VH from nanocarrier in simulated intestinal fluid (SIF) and in simulated gastric fluid (SGF) was studied. The release mechanism was considered by applying various mathematical models to the in vitro release curves. Nearly 40% and 99% of VH were released in SIF (pH = 7.4) and SGF (pH = 1.2) at 6 h, respectively. The cytotoxicity of PAH-GO/PGTPA/DHB Dendr was investigated via 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and apoptosis methods using PC-12 cell lines.