Stimuli-responsive smart nanocarriers for skin drug delivery

Nanomaterials have improved skin drug delivery by facilitating the creation of smart, stimuli-responsive nanocarriers with increased therapeutic effectiveness. Internal or external stimuli can activate these systems, enabling controlled drug release. Internal stimuli-responsive nanocarriers use pathological alterations in diseased skin, like variations in pH, oxidative stress, enzymatic activity, or glucose concentrations, to trigger drug release exactly at the target sites. Conversely, external stimuli-responsive systems depend on physical stimuli such as temperature, light, electric fields, ultrasound, or magnetic fields, facilitating controlled release at specific times and sites. Collectively, these methods increase localized therapeutic precision, reduce systemic adverse effects, and improve therapeutic outcomes in dermatology. This review explores stimuli-responsive nanocarriers, focusing specifically on their use in skin drug delivery, highlighting their therapeutic advantages and limitations, and summarizing several studies using single- and dual-stimuli responsive systems for skin delivery in the treatment of dermatological disorders. The review also provides a critical overview of the analytical methods used to evaluate these nanocarriers, including in vitro, ex vivo, and in vivo models; physiochemical characterization; and advanced microscopic imaging, it also outlines their advantages and limitations. Finally, the paper concludes by delineating the present status of the field and identifying key challenges for future research to enhance the therapeutic use of stimuli-responsive nanocarriers for skin drug delivery.