Maleimide-acetylcholine headed bolaamphiphilic vesicles made from ricinoleic acid: Prospective active targeted drug delivery systems

[Display omitted] •Synthesis of asymmetric bolaamphiphiles with different head groups from ricinoleic acid.•Bola with ACh and MAL head groups can self-assemble into positively charged nano-size vesicles.•Vesicles are able to encapsulate water soluble compounds with good efficiency.•Monolayer membrane of the vesicles is symmetrical with antiparallel packing.•Bola with ACh and MAL head groups is a precursor of a plethora of asymmetric bolas via the thiol-ene reaction. Based on ricinoleic acid, two asymmetric bolaamphiphiles with unsymmetrical hydrophobic skeletons and two different hydrophilic head groups were designed and synthesized. The first bola compound had acetylcholine (ACh) and maleimide (MAL) head groups while the second was derived from the first bolaamphiphile by thiol-ene conjugation of its maleimide moiety with l-glutathione and possessed ACh and l-glutathione-MAL head groups. Both synthetic bolaamphiphiles were characterized by common spectroscopic methods. The asymmetric bola compound with ACh and MAL head groups was investigated for its ability to self-aggregate into nanoparticles and showed to form in aqueous media nano-sized vesicles that were stable, positively charged and had symmetrical monolayer membrane with antiparallel packing. These vesicles prepared with or without membrane stabilizers such as cholesterol (CHOL) and cholesteryl hemisuccinate (CHEMS) were able to encapsulate carboxyfluorescein (CF), a water soluble and self-quenching marker and particularly those without additives were more CF encapsulating. The synthesis of bolaamphiphile with ACh-l-glutathione-MAL head groups gives evidence that the bola with ACh and MAL head groups can be utilized as a precursor of a plethora of asymmetric bolas.