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Abstract
Due to an increase in incidences of multidrug-resistant bacteria and the formidable barrier of the stratum corneum, effective management of chronic, deep thermal pathologies is challenging. Inadequate bioavailability, quick metabolism of drugs, and insufficient penetration are frequently presented by preparations of conventional topical dosage forms (Guy, 2024). Stimuli-responsive supramolecular nanogels have been developed as an advanced category of hybrid platforms that combine a resilient three-dimensional framework of cross-linked polymeric network with the dynamic modularity of host-guest chemistry to overcome these limitations (Kesharwani et al., 2023). This research reviews the incorporation of macrocyclic hosts, specifically cyclodextrins, cucurbiturils, and pillararenes, into nanogel structures for drug delivery (Saji, 2022). Non-covalent and reversible interactions are applied in these systems to aid in significant loading of the drug and spatial-temporal release, which is induced by localized oxidative stress and infected wound environment with acidic pH, enhancing activities of enzymes such as matrix metalloproteinases and gelatinases (T. Das, Das, Sultana, & Swain, 2025; Dong et al., 2023). Furthermore, we evaluate the mechanism by which these supramolecular assemblies penetrate the dermis through lipid fluidization and hair follicle shunting, which is supported by evidence from ex vivo confocal Raman spectroscopy and Franz diffusion investigations (X. Wang, Ma, Li, & Yang, 2024). This review provides a critical examination of developments in biofilm eradication, cytocompatibility, and regulatory problems faced during the practical application of these smart nanotherapeutic device.