All-Natural, Robust, and pH-Responsive Glycyrrhizic Acid-Based Double Network Hydrogels for Controlled Nutrient Release

Abstract

Supramolecular hydrogels self-assembled from naturally occurring small molecules (e.g., glycyrrhizic acid, GA) are promising materials for controlled bioactive delivery due to their facile fabrication processes, excellent biocompatibility, and versatile stimuli-responsive behaviors. However, most of these natural hydrogels suffer from poor mechanical strength and processability for practical applications. In this work, through adopting a multicomponent gel approach, we developed a novel mechanically robust GA-based hydrogel with an interpenetrating double network (DN) that is composed of a Ca2+-enhanced hydrogen-bond supramolecular GA nanofibril (GN) network and a Ca2+cross-linked natural polysaccharide sodium alginate (ALG) network. Compared to the single GN network (SN) hydrogel, the GN-ALG hybrid hydrogels (GN-ALG-DN) with the hierarchical double-network structure possess excellent mechanical properties and shaping adaptation, encouraging small and large amplitude oscillatory shear (SAOS and LAOS) rheological performances, better thermal stability, higher resistance to large compression deformations, and lower swelling behaviors. Furthermore, the GN-ALG-DN hydrogels exhibit a pH-responsive and sustained release behavior of nutrients (i.e., vitamin B12, VB12), showing a faster VB12 release rate with a higher swelling ratio in an alkaline condition (pH 7.5) than in an acidic condition (pH 2.5). This is ascribed to the fact that the higher dissociation degree of carboxylic groups in GA and ALG molecules in an alkaline environment induces the erosion and looseness of the self-assembled GN network and the ionic-cross-linked ALG network, which can lead to the decomposition of the hybrid hydrogels and thereby increases the release of nutrients. Cytotoxicity tests further demonstrate the excellent biocompatibility of the GN-ALG-DN hydrogels. This study highlights the design of robust shaped and structured supramolecular hydrogels from natural herb small molecules, which can serve as solid, edible, and stimuli-responsive active cargo delivery platforms for food, biomedical, and sustainable applications.

A quadruple-stimuli responsive supramolecular hydrogel constructed from a poly(acrylic acid) derivative and β-cyclodextrin dimer

“…Moreover, ferrocene (Fc), a common redox-responsive compound, can act as a hydrophobic guest for b-CD in its reduced state and undergo a reversible one-electron oxidation. [49][50][51][52][53][54] For example, an electroactive supramolecular gel has been fabricated through the host-guest interaction between b-CD and Fc, in which the reversible sol-gel phase transition can be triggered by various stimuli, such as chemical redox, applied voltage and temperature. 55 Notably, the redox and electro-responsive properties make Fc suitable in the application of control release.…”

A natural food-grade supramolecular self-assembly system for creation of hierarchically structured hydrogels

“…13 Considering the safe and green applications in functional food and biomedical fields, it is highly desirable to develop supramolecular hydrogels by the use of naturally occurring, edible ingredients as building blocks that have high bioactivity, biocompatibility, and biodegradability. [14][15][16] Glycyrrhizic acid (GA) is a naturally occurring compound extracted from licorice root that possesses various biological activities, including anti-inflammatory, hepatoprotective, anticancer, and antiviral activities. [17][18][19] From the point of view of chemical structure, GA is a chiral amphiphilic molecule consisting of a hydrophobic triterpenoid glycoside (18β-glycyrrhetinic acid) and a hydrophilic diglucuronic acid unit.…”