Chengqun Yu

Radix Paeoniae Alba (RPA) has been used extensively in Chinese traditional medicine to treat gastrointestinal disorders, immune-modulating diseases, cancers, and numerous other conditions. A few of its active components include paeoniflorin, albiflorin, lactiflorin, and catechin. However, their therapeutic effectiveness is compromised by poor pharmacokinetic profiles, low oral bioavailability, short half-lives, and poor aqueous solubility. In this study, hydroxyethyl cellulose-grafted-2-acrylamido-2-methylpropane sulfonic acid (HEC-g-AMPS) hydrogels were successfully prepared for the controlled release of Radix Paeonia Alba-solid dispersion (RPA-SD). A total of 43 compounds were identified in RPA-SD using UHPLC-Q-TOF-MS analysis. The hydrogel network formation was confirmed by FTIR, TGA, DSC, XRD, and SEM. Hydrogels’ swelling and drug release were slightly higher at pH 1.2 (43.31% swelling, 81.70% drug release) than at pH 7.4 (27.73% swelling, 72.46% drug release) after 48 h. The gel fraction, drug release time and mechanical strength of the hydrogels increased with increased polymer and monomer concentration. Furthermore, the hydrogels were porous (84.15% porosity) and biodegradable (8.9% weight loss per week). Moreover, the synthesized hydrogels exhibited excellent antimicrobial and antioxidative properties.

Oxidants play a crucial role in the development of oxidative stress, which is linked to disease progression. Ellagic acid is an effective antioxidant with applications in the treatment and prevention of several diseases, since it neutralizes free radicals and reduces oxidative stress. However, it has limited application due to its poor solubility and oral bioavailability. Since ellagic acid is hydrophobic, it is difficult to load it directly into hydrogels for controlled release applications. Therefore, the purpose of this study was to first prepare inclusion complexes of ellagic acid (EA) with hydroxypropyl-β-cyclodextrin and then load them into carbopol-934-grafted-2-acrylamido-2-methyl-1-propane sulfonic acid (CP-g-AMPS) hydrogels for orally controlled drug delivery. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) were used to validate ellagic acid inclusion complexes and hydrogels. There was slightly higher swelling and drug release at pH 1.2 (42.20% and 92.13%) than at pH 7.4 (31.61% and 77.28%), respectively. Hydrogels had high porosity (88.90%) and biodegradation (9.2% per week in phosphate-buffered saline). Hydrogels were tested for their antioxidant properties in vitro against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Additionally, the antibacterial activity of hydrogels was demonstrated against Gram-positive bacterial strains (Staphylococcus aureus and Escherichia coli) and Gram-negative bacterial strains (Pseudomonas aeruginosa).

Puerarin has been reported to have anti-inflammatory, antioxidant, immunity enhancement, neuroprotective, cardioprotective, antitumor, and antimicrobial effects. However, due to its poor pharmacokinetic profile (low oral bioavailability, rapid systemic clearance, and short half-life) and physicochemical properties (e.g., low aqueous solubility and poor stability) its therapeutic efficacy is limited. The hydrophobic nature of puerarin makes it difficult to load into hydrogels. Hence, hydroxypropyl-β-cyclodextrin (HP-βCD)-puerarin inclusion complexes (PIC) were first prepared to enhance solubility and stability; then, they were incorporated into sodium alginate-grafted 2-acrylamido-2-methyl-1-propane sulfonic acid (SA-g-AMPS) hydrogels for controlled drug release in order to increase bioavailability. The puerarin inclusion complexes and hydrogels were evaluated via FTIR, TGA, SEM, XRD, and DSC. Swelling ratio and drug release were both highest at pH 1.2 (36.38% swelling ratio and 86.17% drug release) versus pH 7.4 (27.50% swelling ratio and 73.25% drug release) after 48 h. The hydrogels exhibited high porosity (85%) and biodegradability (10% in 1 week in phosphate buffer saline). In addition, the in vitro antioxidative activity (DPPH (71%), ABTS (75%), and antibacterial activity (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) indicated the puerarin inclusion complex-loaded hydrogels had antioxidative and antibacterial capabilities. This study provides a basis for the successful encapsulation of hydrophobic drugs inside hydrogels for controlled drug release and other purposes.

Oxidants play a significant role in causing oxidative stress in the body, which contributes to the development of diseases. Rutin—a powerful antioxidant—may be useful in the prevention and treatment of various diseases by scavenging oxidants and reducing oxidative stress. However, low solubility and oral bioavailability have restricted its use. Due to the hydrophobic nature of rutin, it cannot be easily loaded inside hydrogels. Therefore, first rutin inclusion complexes (RIC) with hydroxypropyl-β-cyclodextrin (HP-βCD) were prepared to improve its solubility, followed by incorporation into xanthan gum-based (hydroxypropyl methylcellulose-grafted-2-acrylamido -2-methyl-1-propane sulfonic acid) hydrogels for controlled drug release in order to improve the bioavailability. Rutin inclusion complexes and hydrogels were validated by FTIR, XRD, SEM, TGA, and DSC. The highest swelling ratio and drug release occurred at pH 1.2 (28% swelling ratio and 70% drug release) versus pH 7.4 (22% swelling ratio, 65% drug release) after 48 h. Hydrogels showed high porosity (94%) and biodegradation (9% in 1 week in phosphate buffer saline). Moreover, in vitro antioxidative and antibacterial studies (Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli) confirmed the antioxidative and antibacterial potential of the developed hydrogels.

In this study, chitosan (CS) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS)-based hydrogels were formulated by the free radical polymerization technique for the controlled release of gallic acid. Fourier transform infrared spectroscopy (FTIR) confirmed the successful preparation and loading of gallic acid within the hydrogel network. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed the increased thermal stability of the hydrogels following the crosslinking and polymerization of chitosan and AMPS. In X-ray diffraction analysis (XRD), the crystallinity of the raw materials decreased, indicating strong crosslinking of the reagents and the formation of a new polymeric network of hydrogels. Scanning electron microscopy (SEM) revealed that the hydrogel had a rough, dense, and porous surface, which is consistent with the highly polymerized composition of the hydrogel. After 48 h, the hydrogels exhibited higher swelling at pH 1.2 (swelling ratio of 19.93%) than at pH 7.4 (swelling ratio of 15.65%). The drug release was analyzed using ultraviolet-visible (UV-Vis) spectrophotometer and demonstrated that after 48 h, gallic acid release was maximum at pH 1.2 (85.27%) compared to pH 7.4 (75.19%). The percent porosity (78.36%) and drug loading increased with the increasing concentration of chitosan and AMPS, while a decrease was observed with the increasing concentration of ethylene glycol dimethyl methacrylate (EGDMA). Crosslinking of the hydrogels increased with concentrations of chitosan and EGDMA but decreased with AMPS. In vitro studies demonstrated that the developed hydrogels were biodegradable (8.6% degradation/week) and had antimicrobial (zone of inhibition of 21 and 16 mm against Gram-positive bacteria Escherichia coli and Staphylococcus aureus as well as 13 mm against Gram-negative bacteria Pseudomonas aeruginosa, respectively) and antioxidant (73% DPPH and 70% ABTS) properties. Therefore, the prepared hydrogels could be used as an effective controlled drug delivery system.

Traditional wound dressings often cannot treat wounds caused by bacterial infections or other wound types that are insensitive to these wound treatments. Therefore, a biodegradable, bioactive hydrogel wound dressing could be an effective alternative option. The purpose of this study was to develop a hydrogel membrane comprised of sodium alginate, polyvinyl alcohol, acrylic acid, and gallic acid for treating skin wounds. The newly developed membranes were analyzed using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), sol-gel fraction, porosity, mechanical strength, swelling, drug release and data modelling, polymeric network parameters, biodegradation, and antioxidation (DPPH and ABTS) and antimicrobial activity against Gram-positive and negative bacteria. The results revealed that hydrogel membranes were crosslinked successfully and had excellent thermal stability, high drug loading, greater mechanical strength, and exhibited excellent biodegradation. Additionally, the swelling ability and the porosity of the surface facilitated a controlled release of the encapsulated drug (gallic acid), with 70.34% release observed at pH 1.2, 70.10% at pH 5.5 (normal skin pH), and 86.24% at pH 7.4 (wounds pH) in 48 h. The gallic acid-loaded hydrogel membranes showed a greater area of inhibition against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli bacteria as well as demonstrated excellent antioxidant properties. Based on Franz cell analyses, the permeation flux of the drug from optimized formulations through mice skin was 92 (pH 5.5) and 110 (pH 7.4) μg/cm²·h⁻¹. Moreover, hydrogel membranes retained significant amounts of drug in the skin for 24 h, such as 2371 (pH 5.5) and 3300 µg/cm² (pH 7.4). Acute dermal irritation tests in rats showed that hydrogel membranes were nonirritating. Hydrogel membranes containing gallic acid could be an effective option for improving wound healing and could result in faster wound healing.

Alzheimer’s disease is the most common neurodegenerative disease, characterized by memory loss and cognitive dysfunction. Raspberry fruits contain polyphenols which have antioxidant and anti-inflammatory properties. In this study, we used molecular imprinting technology to efficiently isolate phenolic components from the raspberry ethyl acetate extracts. Six phenolic components (ellagic acid, tiliroside, kaempferol-3-o-rutoside, gallic acid, ferulic acid and vanillic acid) were identified by UPLC-Q-TOF-MS analysis. Molecular docking was used to predict the anti-inflammatory effects and anti-Alzheimer’s potential of these isolated compounds, which showed a good binding ability to diseases and related proteins. However, the binding energy and docking fraction of ellagic acid, tiliroside, and kaempferol-3-o-rutoside were better than those of gallic acid, ferulic acid and vanillic acid. Additionally, by studying the effects of these six phenolic components on the LPS-induced secretion of inflammatory mediators in murine microglial (BV2) cells, it was further demonstrated that they were all capable of inhibiting the secretion of NO, IL-6, TNF-α, and IL-1β to a certain extent. However, ellagic acid, tiliroside, and kaempferol-3-o-rutoside have better inhibitory effects compared to others. The results obtained suggest that the phenolic components extracted from ethyl acetate extracts of raspberry by molecularly imprinted polymers have the potential to inhibit the progression of Alzheimer’s disease.