Surface modification of graphene oxide by functionalized dendritic polyesters based on phthalic acid and pentaerythritol as a novel nanoplatform for sustained drug delivery: Statistical optimization using response surface methodology and release kinetics modelling

Abstract

In this work, the third generation of polyester dendrimers was synthesized by conjugating phthalic acid and pentaerythritol on the graphene oxide surface. After the esterification reaction, 3, 5-dinitrobenzoyl chloride was grafted to the polyester dendrimer and used as a nanocarrier for the antibiotic-sustained delivery of the metronidazole. The success of the synthesis was confirmed by using various techniques. The batch sorption test was conducted according to the variables set by the central composite design under response surface methodology. The statistically optimized sorption efficiency (95.11%) was attained at pH= 5, 15 µg mL−1 concentration, and a contact time of 15 min. This data indicated that the pseudo-second-order kinetic and Langmuir isotherm models had greater correlation coefficients (R2) of 0.9980 and 0.9995, respectively than the other non-linear models. Based on the thermodynamic study such as ΔH°, ΔG°, and ΔS°, the adsorption efficiency of drug by nanoadsorbent was an endothermic (ΔH°= 16121.68 J mol−1), spontaneous process (ΔG° = −7.83 to 9.84 kJ mol−1), and entropy driven (ΔS° = 80.35 J mol−1K−1). Nearly 98.92% of the drug was released in simulated intestinal fluid, pH= 7.4, in 6 h and 34.96% in simulated gastric fluid, pH= 1.2, in 1 h. The nanocarrier had an encapsulation efficiency of 86.90% and a drug loading of 38.12%. The Korsmeyer-Peppas mathematical model adjusted well to the experimental drug release kinetic profile with non-Fickian diffusion (0.5 <n < 0.9 for all pH). The findings display that the synthesized nanocarrier could be a promising choice for the sustained delivery of metronidazole.