Humic substances, which include humic acid and fulvic acid, are natural biopolymers formed from the decomposition of organic matter. There is growing interest in them because of their diverse potential in the biomedical field. Their complex structures, rich in various functional groups, provide antioxidant, anti-inflammatory, antimicrobial, antiviral, and immunomodulatory properties. Recent studies demonstrate that humic substances can scavenge reactive oxygen species, modulate cytokine production, inhibit viral fusion, promote wound healing, and enhance gut microbiota balance. Humic acid and fulvic acid also exhibit anticancer activity by inducing apoptosis in tumor cells, while protecting healthy tissues from oxidative stress. Furthermore, their chelating capacity underlies detoxifying activity and heavy metal binding effects. Despite promising research, variability in composition and potential cytotoxicity under certain conditions emphasize the need for standardized extraction methods and rigorous preclinical evaluation. This review offers a comprehensive overview of the biological effects of humic substances, exploring the mechanisms behind their actions and their potential biomedical applications. It highlights both the benefits and the limitations associated with their use in drug delivery systems.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the management of inflammatory disorders, pain, and fever due to their significant anti-inflammatory and antipyretic properties. However, their long-term use is often associated with multiple adverse effects, including gastric erosion, hemorrhage, and perforation, as well as cardiovascular, hepatic, and renal complications. Indomethacin is a potent NSAID commonly used in the treatment of pain and rheumatoid arthritis. Its poor water solubility, Biopharmaceutics Classification System (BCS) Class II, results in low aqueous solubility and high membrane permeability, and conventional dosage forms often fail to overcome pharmacokinetic limitations and gastrointestinal irritation. To address these drawbacks, alternative indomethacin-loaded drug delivery systems have been developed, which enable controlled release, enhanced solubility, and targeted delivery for improving therapeutic efficacy and safety profile. Nature provides a diverse reservoir of bioactive compounds with significant anti-inflammatory potential, making them promising alternatives or complementary agents to indomethacin. Representative examples include the alkaloids piperine and berberine; the flavonoids oleocanthal and apigenin; and the terpenoids thymoquinone, kahweol, and cafestol; as well as anthraquinones and iridoids. This review summarizes the current evidence on plant-derived anti-inflammatory compounds that may “replace” or act synergistically with indomethacin. In addition, we discuss the pharmacological properties of indomethacin and recent advances in drug delivery systems designed to improve its topical and systemic therapeutic applications.

Metal nanoparticles such as silver nanoparticles (AgNPs) have attracted considerable scientific interest due to their diverse properties, some of which are antimicrobial, anticancer, and wound healing. Plant-mediated green synthesis offers an alternative to conventional physical and chemical methods for the preparation of nanostructures. It uses phytochemicals such as flavonoids, phenols, and alkaloids as natural reducing and capping agents. However, stand-alone green AgNPs face significant limitations, including batch-to-batch variability, colloidal instability, and uncontrolled ion release. This review provides a comparative evaluation of plant-mediated green AgNPs and advanced biohybrid nanostructures—including polymer, lipid, and hydrogel systems. Preparation/synthesis conditions, particle size, zeta potential, and biological applications are summarized. The comparison shows that biohybrid systems significantly improve colloidal stability, enable sustained and tunable drug release, and improve biocompatibility compared to single nanoparticles. In addition, biohybrid systems offer greater formulation flexibility (films, hydrogels, liposomes, nanocomposites) for targeted drug delivery, antimicrobial therapy, and environmental remediation. These findings highlight the potential of green biohybrid AgNPs as next-generation platforms for applications in various fields of life. Along with this, the need for standardized synthesis protocols and comprehensive safety assessments before their clinical application is also highlighted.

This study investigates composition-microstructure-rheology-performance relationships in Carbopol-based emulgels and bigels containing different oils. Optical microscopy revealed polydisperse droplets in liquid paraffin, isopropyl myristate, and almond oil formulations, whereas cetyl alcohol systems exhibited larger, irregular birefringent particles with Maltese cross-like patterns. All formulations showed shear-thinning behavior and predominantly elastic responses (G′ > G″). Cetyl alcohol-based emulgels exhibited higher elastic moduli and viscosity than those containing other oils. Increasing Carbopol concentration from 0.5% to 1% enhanced elasticity and viscosity, while reducing viscosity losses during heating from 10 to 40 °C from 35 to 40% to 11–26%. Bigels containing 20% and 30% oleogel exhibited elastic moduli approximately 20% and 80% higher than the hydrogel, respectively, suggesting possible synergistic mechanical reinforcement. Correlation analysis revealed relationships between rheological parameters, drug release, and spreadability. Viscosities above approximately 150 Pa·s were associated with reduced drug release, while moderate viscosity favored a balance between structural integrity, spreadability, and release performance. The absence of visible changes after 12 months of storage was consistent with temperature-ramp rheology results, suggesting potential use as a preliminary screening tool for formulation stability. Overall, oil phase selection, phase structuring, and Carbopol concentration enable tailoring stable and functional emulgel and bigel formulations for pharmaceutical and cosmetic applications.

The development of effective topical drug delivery systems remains a key challenge in wound management, particularly for bioactive compounds with limited skin permeability. In this study, a nanostructured bigel system incorporating sodium humate-loaded ultra-deformable vesicles (UDVs) was developed and evaluated for wound healing applications. Sodium humate-loaded UDVs were prepared using a thin-layer hydration method, and the influence of key technological parameters (phospholipid/glycerol concentrations, sonication time) on vesicle size and encapsulation efficiency was investigated. An optimized UDV formulation characterized by small particle size, high stability, and high drug encapsulation efficiency was selected and incorporated into a bigel composed of hydroxypropyl methylcellulose hydrogel and andiroba oil oleogel. The developed bigels were characterized in terms of microstructure, physical stability, pH, spreadability, and rheological behavior, demonstrating suitable properties for dermal application. In vivo wound healing evaluation in rat wound models revealed that bigels containing sodium humate-loaded UDVs significantly enhanced wound closure and tissue regeneration compared to control and reference treatments. Histopathological analysis confirmed improved granulation tissue formation and complete epithelialization. Overall, the results demonstrate that the proposed UDV-loaded hybrid bigel represents a promising nanostructured platform for enhanced dermal delivery and wound healing therapy.