Developing and utilizing effective local antimicrobial agents can help treat periodontitis while minimizing the risks associated with systemic antibiotic use. Recent studies have shown that the mucosal adhesion properties of hydrogels can play a potential role in the treatment of periodontitis. The hydrogel can improve the contact and retention time of drugs in the periodontal pocket. Through the adhesion of mucosa, it interacts with the mucin coating surface of epithelium and teeth to form a specific interface force. The hydrogel exhibits strong mucosal adhesion (adhesion strength: 5-6 N/cm²) and prolonged retention in periodontal pockets (≥6 h), enabling sustained drug release through dynamic sol-gel transitions triggered by pH and reactive oxygen species (ROS). This design overcomes the limitations of poor mechanical stability in conventional formulations. The dynamic balance of oral microbiota plays an important role in maintaining oral health. Probiotics, by colonizing the oral cavity, transform the infected site from an environment rich in inflammatory cytokines to a more benign environment, inhibit harmful pathogenic microorganisms, and contribute to overall health. Microenvironment sensitive hydrogels can perform dynamic sol gel transformation in situ, and can accurately control drug release when exposed to various stimuli (such as temperature change, light, pH change, reactive oxygen species, etc.). Oral probiotics and anti-inflammatory drugs are encapsulated in hydrogels to inhibit the proliferation and adhesion of oral pathogens by planting in the mouth and producing metabolites, effectively preventing and treating oral diseases.

Background: Frostbite injury creates an ischemic, hypoxic, and acidic microenvironment that often triggers severe oxidative stress and inflammation. Current therapeutic approaches are limited by low drug delivery efficiency and an inability to adequately regulate multiple pathological pathways. Although oxyresveratrol (OR) exhibits excellent antioxidant and anti-inflammatory activities, its application is hampered by poor aqueous solubility and low stability. Methods: We constructed Oxyresveratrol@Zeolitic Imidazolate Framework-8 nanoparticles (OR@ZIF-8) and further embedded them in a sodium hyaluronate (HA) matrix to form an OR@ZIF-8@HA composite hydrogel. The physicochemical properties and pH-responsive drug release behavior of the system were characterized. Its antioxidant activity, ability to promote cell migration, and capacity to modulate macrophage polarization were evaluated in cellular assays. The therapeutic efficacy was further investigated using a mouse frostbite model, with wound repair analyzed via histological staining. Results: The OR@ZIF-8 nanoparticles achieved a cumulative release rate of 75.46 ± 3.68% under acidic conditions within 36 h. In vitro experiments demonstrated that the formulation significantly scavenged TNF-α and IL-6, by 161.85 ± 19.43% and 125.37 ± 12.65%, respectively, and increased the level of IL-10 by 44.97 ± 4.57%. In a scratch assay, it promoted wound healing, achieving a closure rate of 97.55 ± 2.77% after 36 h. In vivo studies revealed that the OR@ZIF-8@HA treatment group achieved a wound healing rate of 96.14 ± 4.12% on day 14. Conclusions: The OR@ZIF-8@HA composite hydrogel effectively overcomes the limitations of OR application via intelligent pH-responsive delivery. Through synergistic multi-mechanistic actions, it significantly accelerates frostbite wound healing, offering a novel and efficient therapeutic strategy for frostbite management.

A new derivatization high-performance liquid chromatography method with ultraviolet detection was developed and validated for the quantitative analysis of methanesulfonate genotoxic impurities in an innovative drug for the treatment of non-alcoholic fatty liver disease. In this study, sodium dibenzyldithiocarbamate was used as a derivatization reagent for the first time to enhance the sensitivity of the analysis, and NaOH aqueous solution was chosen as a pH regulator to avoid the interference of the drug matrix. Several key experimental parameters of the derivatization reaction were investigated and optimized. In addition, specificity, linearity, precision, stability, and accuracy were validated. The determined results of the samples were consistent with those obtained from the derivatization gas chromatography–mass spectrometry analysis. Thus, the proposed method is a reliable and practical protocol for the determination of trace methanesulfonate genotoxic impurities in drugs containing mesylate groups.

Methyl 7,7-dimethoxy-5-(morpholinomethyl)-[4,4-bibenzo[d][1,3] dioxole]-5-carboxylate methanesulfonate (IMM) is an innovative drug for the treatment of nonalcoholic fatty liver disease (NAFLD) owing to its high efficacy and low toxicity. In this study, five minor impurities (I, II, III, IV, and V) were identified and analyzed using spectroscopic evidence, chemical synthetic methods, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The impurities included hydrolysates and oxidation by-products extracted from both the drug in its final formulation and during synthesis. Toxicity prediction revealed potential carcinogenicity of impurity V containing an N-oxygen fragment. A reliable and selective HPLC method for the quantitative analysis of impurities IIV and a sensitive HPLC-MS/MS method for potential genotoxic impurity V were developed and optimized. The methods were validated based on the International Council for Harmonization guidelines. Satisfactory linearity was obtained for the analytes over the range of 0.12.0μg/mL for impurities IIV and 0.330.0ng/mL for impurity V, and in all cases, the fitting correlation coefficients exceeded 0.999. The obtained limits of detection values were 0.05ng/mL and 0.005μg/mL for impurity V and impurities IIV, respectively. The precision and repeatability of the methods were less than 1.08 and 8.72 for each impurity. The recovery percentages of all impurities were in the range of 91.18111.27, with the relative standard deviation of less than 3.69. The greenness assessment of the HPLC method and the HPLC-MS/MS method were evaluated by using AGREE software with a score value of 0.72 and 0.68, respectively. The recommended procedures that were accurate, specific, and ecofriendly were applied to the existing active pharmaceutical ingredients of IMM, and they generated satisfactory results.

This study aimed to develop extended–release tablets containing 25 mg IMM−H014, an original drug formulated by a direct powder pressing method based on pharmaceutical–grade hydrophilic matrix polymers, such as hydroxypropyl methylcellulose, to establish an in vitro−in vivo corre-lation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were de-termined in five dissolution media, in which the drug released from the hydrophilic tablets fol-lowed Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate buffer saline medium (pH 7.5) for further 24 h. Accelerated stability studies (40°C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmaco-kinetics study in beagle dogs showed that compared to the IMM−H014 immediate release prep-aration, the maximum plasma concentration of the extended release (ER) preparation was sig-nificantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on an area under curve, indicating that the optimal formulation has an obvious ER profile. And a good IVIVC was established, which could be used to predict in vivo pharmacokinetics from the formulation composition.

This study aimed to develop extended-release tablets containing 25 mg IMM-H014, an original drug formulated by a direct powder pressing method based on pharmaceutical-grade hydrophilic matrix polymers such as hydroxypropyl methylcellulose, to establish an in vitro–in vivo correlation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single-factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were determined in five dissolution media, in which the drug released from the hydrophilic tablets followed the Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate-buffered saline medium (pH 7.5) for a further 24 h. Accelerated stability studies (40 °C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmacokinetics study in beagle dogs showed that compared to the IMM-H014 immediate release preparation, the maximum plasma concentration of the extended-release (ER) preparation was significantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on the area under curve, indicating that the optimal formulation has an obvious ER profile, and a good IVIVC was established, which could be used to predict in vivo pharmacokinetics based on the formulation composition.