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However, poor incorporation of hydrophobic drugs into hydrophilic tNGs limits the therapeutic efficiency. To address this challenge, \u03b2\u2010cyclodextrins (\u03b2\u2010CD) are functionalized by hyperbranched polyglycerol serving as crosslinkers (hPG\u2010\u03b2CD) to fabricate \u03b2CD\u2010tNGs. This novel construct exhibits augmented encapsulation of hydrophobic drugs, shows the appropriate thermal response to dermal administration, and enhances the dermal penetration of payloads. The structural influences on the encapsulation capacity of \u03b2CD\u2010tNGs for hydrophobic drugs are analyzed, while concurrently retaining their efficacy as skin penetration enhancers. Various synthetic parameters are considered, encompassing the acrylation degree and molecular weight of hPG\u2010\u03b2CD, as well as the monomer composition of \u03b2CD\u2010tNGs. The outcome reveals that \u03b2CD\u2010tNGs substantially enhance the aqueous solubility of Nile Red elevating to 120\u00a0\u00b5g\u00a0mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    and augmenting its dermal penetration up to 3.33\u00a0\u00b5g\u00a0cm\n                    <jats:sup>\u22122<\/jats:sup>\n                    . Notably, the acrylation degree of hPG\u2010\u03b2CD plays a significant role in dermal drug penetration, primarily attributed to the impact on the rigidity and hydrophilicity of \u03b2CD\u2010tNGs. Taken together, the introduction of the functionalized \u03b2\u2010CD as the crosslinker in tNGs presents a novel avenue to enhance the efficacy of hydrophobic drugs in dermatological applications, thereby offering promising opportunities for boosted therapeutic outcomes.\n                  <\/jats:p>","DOI":"10.1002\/smll.202311166","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T22:39:42Z","timestamp":1714603182000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Polyglycerol\u2010Functionalized \u03b2\u2010Cyclodextrins as Crosslinkers in Thermoresponsive Nanogels for the Enhanced Dermal Penetration of Hydrophobic Drugs"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9108-223X","authenticated-orcid":false,"given":"Huiyi","family":"Wang","sequence":"first","affiliation":[{"name":"POLYMAT, Applied Chemistry Department Faculty of Chemistry 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