Synthesis of quercetin based self-assembling supramolecular amphiphiles for amphotericin B delivery

Self-assembling amphiphilic molecules have been the subject of greater scientific interest owing to their applications in drug delivery. The available amphiphilic molecules that have been in practice for drug delivery application face issues like high cost, stability, and compatibility, thus there is a need to synthesize efficient amphiphiles from renewable resources. This project was designed to synthesize amphiphiles with diverse lipophilicity from naturally occurring flavonoid. Quercetin was selected as a polar head of amphiphile and was successfully derivatized with dodecyl bromide where the alkyl chain regio-selectively attached with different positions of quercetin hydroxyl (OH) groups. These compounds were characterized by MALDI, H-1 NMR, C-13 NMR, HMBC, and FTIR. Thin film hydration method was used for the synthesis of vesicles having their diameter in nano-ranges (300-400 nm). Amphotericin B was used as a host drug and the amphiphiles were able to entrap more than 90% drug. The nanoformulation was further analyzed by FTIR, UV-visible spectroscopy, DLS, and AFM to assess their stability, homogeneity, surface charge, CMC, and morphology. This analysis suggested that the amphiphiles are efficient for encapsulating the drug with good stability of the suspension. The drug loaded self-assembled nanostructures were administrated orally in rabbits to check oral bioavailability of amphotericin B. Results confirmed that the drug loaded self-assembled novel amphiphile baased vesicles enhanced oral bioavailability of the hydrophobic drug. (C) 2021 Elsevier B.V. All rights reserved.