Niosomes as Vesicular Carriers: From Formulation Strategies to Stimuli-Responsive Innovative Modulations for Targeted Drug Delivery

Niosomes (NIOs), a class of nanovesicular drug delivery system, have garnered significant attention due to their unique architecture, resulting from the self-assembly of non-ionic surfactants (with or without cholesterol) in aqueous media. This bilayered structure enables the encapsulation of both hydrophilic agents in the aqueous core and lipophilic compounds within the lipid bilayer, offering remarkable versatility in therapeutic applications. This article provides an overview of the key principles underlying niosomal formulations, including their composition, preparation methods, formulation conditions and the critical physicochemical parameters influencing vesicle formation and performance. Special emphasis is placed on recent innovations in surface and content modifications that have led to the development of stimuli-responsive niosomal systems, with precise and controlled drug release. These smart carriers are designed to respond to endogenous stimuli (such as pH variations, redox gradients, enzymatic activity, or local temperature changes in pathological sites), as well as to exogenous triggers (including light, ultrasound, magnetic or electric fields, and externally applied hyperthermia), thereby enhancing therapeutic precision. These surface and content modulation strategies effectively transform conventional NIOs into intelligent, stimuli-responsive platforms, reinforcing their innovative role in drug delivery and highlighting their significant potential in the development of smart nanomedicine.