Enhanced topical delivery of dexamethasone by β-cyclodextrin decorated thermoresponsive nanogels

Abstract

Highly hydrophilic, responsive nanogels are attractive as potential systems for the topical delivery of bioactives encapsulated in their three-dimensional polymeric scaffold. Yet, these drug carrier systems suffer from drawbacks for efficient delivery of hydrophobic drugs. Addressing this, β-cyclodextrin (βCD) could be successfully introduced into the drug carrier systems by exploiting its unique affinity toward dexamethasone (DXM) as well as its role as topical penetration enhancer. The properties of βCD could be combined with those of thermoresponsive nanogels (tNGs) based on dendritic polyglycerol (dPG) as a crosslinker and linear thermoresponsive polyglycerol (tPG) inducing responsiveness to temperature changes. Electron paramagnetic resonance (EPR) studies localized the drug within the hydrophobic cavity of βCD by differences in its mobility and environmental polarity. In fact, the fabricated carriers combining a particulate delivery system with a conventional penetration enhancer, resulted in an efficient delivery of DXM to the epidermis and the dermis of human skin ex vivo (enhancement compared to commercial DXM cream: ∼2.5 fold in epidermis, ∼30 fold in dermis). Furthermore, DXM encapsulated in βCD tNGs applied to skin equivalents downregulated the expression of proinflammatory thymic stromal lymphopoietin (TSLP) and outperformed a commercially available DXM cream.

Reactive Precursor Particles as Synthetic Platform for the Generation of Functional Nanoparticles, Nanogels, and Microgels

“…SPAAC proved to be especially useful for the conjugation and incorporation of specific moieties on the surface of colloidal systems. One example was presented by Calderón and co‐workers who developed a nanogel precursor by thermonanoprecipitation . The precursor particles were prepared via crosslinking of azide modified linear thermoresponsive polyglycerol with dendritic dPG‐(1R,8S,9s)‐bicyclo[6.1.0]non‐4‐yn‐9‐ylmethyl (4‐nitrophenyl) carbonates (dPG‐BCN) that act as a crosslinker.…”

“…This strategy allowed the introduction of βCD moieties without changing the colloidal properties of the carrier. βCDs gained interest since they are characterized to have a hydrophobic pocket, giving the possibility for the encapsulation of hydrophobic drugs into a hydrophilic system . Even though reactive groups are available in the interior as well as on the surface of the nanogels, the authors describe a surface decoration only.…”

“…Synthesis route for the preparation of β‐CD grafted thermoresponsive nanogels. Reproduced with permission . Copyright 2018, Royal Society of Chemistry.…”

Hydroxypropyl-β-cyclodextrin-containing hydrogel enhances skin formononetin permeation/retention

“…The isoflavone‐aglycone, which has a polyphenolic structure, has low solubility in water. Studies have shown that in skin topical use, cyclodextrins have been reported as promoters of skin permeation of bioactive molecules with unique biocompatibility characteristics . Several mechanisms have been assigned to explain the skin permeation promoter effect observed with the use of cyclodextrins .…”

“…Studies have shown that in skin topical use, cyclodextrins have been reported as promoters of skin permeation of bioactive molecules with unique biocompatibility characteristics. [13] Several mechanisms have been assigned to explain the skin permeation promoter effect observed with the use of cyclodextrins. [14][15][16] Our previous report has been showed that the use of physical mixture of 3-O-methylquercetin : b-cyclodextrin instead the corresponding complex resulted in better permeation profile from HPMC hydrogel.…”