Structurally robust and biodegradable amide-linked dendritic amphiphiles for pH-responsive nanocarriers for enhanced hydrophobic drug delivery​

Chemical Biology Letters

Read More

Keywords: item categories 

The development of biocompatible and structurally robust amphiphilic nanocarriers is crucial for enhancing the solubility, stability, and targeted delivery of poorly water-soluble therapeutics. In this study, we report the design, synthesis, and physicochemical evaluation of four new non-ionic dendritic amphiphiles derived from glycerol-based dendrons incorporating biodegradable amide linkers as pH-sensitive moieties. These amphiphiles were synthesized through a modular approach, employing a polyglycerol core and hydrophobic alkyl chains of varying lengths introduced via amide bond formation. Structures were confirmed by using FTIR, ¹H NMR, and ¹³C NMR spectroscopy data. Owing to their amphiphilic nature, the molecules spontaneously self-assemble in aqueous media to form well-defined, stable micellar structures, as confirmed by surface tension analysis and dynamic light scattering (DLS). To evaluate their drug delivery potential, pyrene was used as a model hydrophobic guest molecule. Among the synthesised amphiphiles, the C12-G1 dendron demonstrated optimal encapsulation efficiency and was used for a release profile study. Drug release studies conducted under physiological (pH 7.0) and tumor-mimicking acidic (pH 5.3) conditions revealed a sustained release behaviour over 16–24 hours, with a significantly enhanced release under acidic conditions. Comparative analysis with previously developed ester-linked analogs revealed that amide-linked systems exhibit lower critical micelle concentrations (CMC), enhanced stability, and pH responsiveness. This work highlights the potential of amide linkers as a promising carrier for next-generation nanocarriers for hydrophobic drug delivery in biomedical applications.