Construction of thermoresponsive nanogels with various structures for dermal drug delivery.

Abstract

Thermoresponsive nanogels (tNG) are promising candidates for skin drug delivery since they can releasethe encapsulated therapeutics under the physiological skin temperature gradient trigger. This doctoralthesis aims to construct poly(N-isopropylacrylamide)-based tNGs with various structures for differentskin applications. Firstly, tNGs with hollow cavities, named nanocapsules, were fabricated to study theeffect of mechanical properties on dermal drug penetration. The skin penetration assay of BSA-FITCdemonstrated that the softer nanocapsules enable deeper BSA-FITC dermal penetration with a higherintensity. Secondly, ß-cyclodextrin incorporated tNGs were prepared for enhancing the dermal deliveryof hydrophobic drugs, using Nile red as the drug model. A quantitative study and fluorescencecharacterization demonstrated an improved Nile red dermal penetration. The acrylation degree of thecrosslinker was significant for Nile red dermal penetration. Lastly, hybrid yolk-shell tNGs were designedto achieve synergistic therapy. Upconverting nanoparticles were introduced as the cores to convert theNIR light to visible light as the trigger of the photosensitizers. The tNGs displayed effective generation ofreactive oxygen singlets for photodynamic therapy and BSA-FITC penetration for protein therapy.