Vesicle formation by cholesterol based hydrazone tethered amphiphiles: Stimuli responsive dissipation of self-assembly

Abstract

Stimuli are one of the key parameters to achieve a control over the association/dissociation of molecular tectons in self-assemblies. In this present article, we synthesized cholesterol based pH-sensitive hydrazone-tailored low molecular mass amphiphiles (CBH-1-3). The hydrazone residue was modified by varying the carbonyl moieties from aldehyde (benzaldehyde (CBH-1), p-dimethylaminobenzaldehyde (CBH-2)) to ketone (benzophenone (CBH-3)). Microscopic and spectroscopic characterizations were carried out to investigate the pattern of self-aggregation and its morphology. Among these amphiphiles, CBH-1 and CBH-2 were found to form vesicular aggregates through H-type aggregation in 1:3 v/v, DMSO-water having dimension of around 50-120 nm in the case of CBH-1 and ∼150-250 nm for CBH-2. Moreover, low angle X-ray diffraction (XRD) pattern of the self-aggregates confirmed the formation of bilayer vesicles through highly ordered lamellar like structure for the hydrazone-tailored amphiphiles. These vesicles are stable at pH 7.0 and above, however get disassembled at acidic pH (pH < 5.0). This dissipation of the vesicular self-aggregates because of the cleavage of the hydrazone bond under acidic environment was investigated by UV-visible, FTIR and mass spectrometric studies. Moreover, absence of any spherical aggregate in the transmission electron microscopic (TEM) images of the acid treated vesicles confirmed its disintegration in acidic medium. Furthermore, dye encapsulation and its pH-responsive release from the CBH-1 vesicles were tested using doxorubicin as drug.