Synthesis and biocompatibility of self-assembling multi-tailed resorcinarene-based supramolecular amphiphile

Abstract

Nano-vesicles of multi-tailed macrocycle molecules have demonstrated a great ability to enhance the bioavailability of hydrophobic drugs. In this study, amphiphilic multi-tailed resorcinarene (MTR) derivative was synthesised in two steps reaction by O-alkylation of 4-hydroxybenzaldehyde and then condensation with resorcinol. The synthesised amphiphilic macrocycle was characterized by 1H-NMR, FT-IR and mass spectrometry. Self-assembly and aggregation behaviour of amphiphilic macrocycle was studied in aqueous medium and vesicles were characterised for morphology, critical micelle concentration (CMC), size and surface potential and cellular biocompatibility. The self-assembling ability of MTR was used for one-step loading of hydrophobic drug, i.e. clarithromycin. MTR presented a low CMC value, i.e. 0.055 mM and formed niosomal vesicles with a mean diameter of 210 ± 2 nm, narrow size distribution and 65.12 ± 3.31% drug entrapment efficiency. MTR vesicles showed sustained in vitro drug release while maximum drug release was achieved at 8 h. Biocompatibility of MTR was investigated with blood haemolysis and cytotoxicity assays. The results indicated suitability of MRT as amphiphilic macromolecular surfactant.