Nanostructured lipid carrier-incorporated hybrid hydrogels for enhanced betamethasone delivery in atopic dermatitis

Atopic dermatitis (AD) is a multifactorial and widespread skin condition characterized by extreme dryness, intense itching, and compromised skin barrier function due to inflammation. The variability among patients requires constant treatment search for this skin problem, which affects children (20 %) and adults (10 %) worldwide. In this work, the use of hybrid hydrogels prepared from a blend of biocompatible marine kappa−carrageenan polysaccharide and synthetic polyvinyl alcohol polymer was thought to provide a delivery platform for betamethasone to address the features of AD. As a strategy for the local delivery of betamethasone to solve skin inflammation within its layers, this drug was also incorporated into lipid nanoparticles, which were further embedded in the hydrogel matrices to enhance its local effect and avoid side effects. The designed NLC formulations were physicochemically characterized (ca. 200 nm, polydispersity below 0.2, and surface charge of ca. −35 mV), presenting high betamethasone content (>2 mg per NLC formulation, corresponding to ≥ 75 % entrapment efficiency), and the hydrogels showed pseudoplastic rheological behavior. Cellular biocompatibility was verified in fibroblasts and keratinocytes in a concentration-dependent manner (tested up to 100 mg mL −1 in hydrogel), with anti-inflammatory potential (downregulating IL-6, IL-8, and TNF-α secretion). Their effects on skin lipids and proteins were monitored through synchrotron-based Fourier-transform infrared microspectroscopy and full-thickness pig ear skin permeation. These hybrid formulations might represent a valuable nano-strategy and pave new treatment options for several manifestations and AD symptoms. • Composite hydrogels with high betamethasone content to treat atopic dermatitis. • Pseudoplastic rheological behaviour that can be applied directly in the skin. • Uncovered anti-inflammatory potential and skin barrier reestablishment. • Hydrates stratum corneum without affecting epidermal lipid organization and order. • Impacts on skin inflammatory disease research, material science and biophysics.