Stimuli-responsive azo-functionalized non-ionic amphiphiles for controlled drug delivery applications

[Display omitted] •Synthesized azo-functionalized amphiphiles using biocompatible building blocks.•Study of nano-sized aggregation of amphiphiles and encapsulation of dye/drug.•Studied stimuli responsive release of guest using UV–Vis light and enzyme.•Evaluated cytotoxicity of the selected amphiphiles using HeLa cell lines. A series of stimuli-responsive non-ionic amphiphiles have been synthesized consisting of n-alkyl/fluoroalkyl chain to impart lipophilicity, and lactose/polyethylene glycol units which confers hydrophilicity. To execute the release of encapsulated guest in a controlled manner, the azo and ester functionalities were incorporated in the synthesized amphiphiles. The ability of the azo unit to undergo trans–cis-trans spatiotemporal isomerization under UV irradiation with subsequent release of the encapsulated guest has been studied in the aqueous solution of amphiphiles at 365 and 254 nm. Furthermore, an immobilized enzyme Candida antarctica lipase (Novozym 435), a hydrolase, was observed to facilitate the cleavage of the ester moiety of the synthesized amphiphiles resulting in the gradual collapse of the nano-aggregates and subsequent release of encapsulated guest. The aggregation and guest encapsulation behaviour of synthesized azo-functionalized amphiphiles were studied by dynamic light scattering (DLS), critical micelle concentration (CMC), and transmission electron microscopy, fluorescence and UV–Vis spectroscopy. Entrapment of hydrophobic drug/dye i.e. curcumin/Nile red in the lipophilic core, their cellular uptake, and consequently the stimuli responsive release of payload demonstrated the potential of these nanostructures in controlled drug delivery applications.