Search Results (43)

This study presents the results of a study of the synthesis and properties of 2-hydroxy-β-cyclodextrin functionalized by silver nanoparticles and its loading with a bioactive component. As a reducing agent and stabilizer, 2-Hydroxy-β-cyclodextrin (2gβCD) was used in the production of silver nanoparticles. The use of 2gβCD-AgNPs in loading molecules of the plant alkaloid lupinine (Lup) and its acetyl derivative (Lac) with bactericidal properties were studied. The formation of Lup-2gβCD-AgNPs and Lac-2gβCD-AgNPs was confirmed by UV spectroscopy and X-ray diffraction spectroscopy (XRD). Transmission electron microscopy (TEM) showed that the synthesized AgNPs had a spherical shape. ¹H-, ¹³C-NMR nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy (FT-IR) confirmed the reduction and encapsulation of AgNPs by 2gβCD. Thermographic data show that the obtained Lup and its derivative inclusion complexes reduced energy barriers. This makes them promising components for thermosensitive functional materials. Encapsulated complexes of Lup and its acetate inclusion with silver nanoparticles demonstrated significantly (p < 0.05) higher antibacterial, cytotoxic, and moderately pronounced analgesic activity. Full article

The mineralocorticoid receptor (MR), traditionally associated with renal function, has also been identified in various extrarenal tissues, including the heart, brain, and dorsal root ganglion (DRG) neurons in rodents. Previous studies suggest a role for the MR in modulating peripheral nociception, with MR activation in rat DRG neurons by its endogenous ligand, aldosterone. This study aimed to determine whether MR, its protective enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), its endogenous ligand aldosterone, and the aldosterone-synthesizing enzyme CYP11B2 are expressed in human DRG neurons and whether they colocalize with key pain-associated signaling molecules as potential targets for genomic regulation. To this end, we performed mRNA transcript profiling and immunofluorescence confocal microscopy on human and rat DRG tissues. We detected mRNA transcripts for MR, 11β-HSD2, and CYP11B2 in human DRG, alongside transcripts for key thermosensitive and nociceptive markers such as TRPV1, the TTX-resistant sodium channel Nav1.8, and the neuropeptides CGRP and substance P (Tac1). Immunofluorescence analysis revealed substantial colocalization of MR with 11β-HSD2 and CGRP, a marker of unmyelinated C-fibers and thinly myelinated Aδ-fibers, in human DRG. MR immunoreactivity was primarily restricted to small- and medium-diameter neurons, with lower expression in large neurons (>70 µm). Similarly, aldosterone colocalized with CYP11B2 and MR with nociceptive markers including TRPV1, Nav1.8, and TrkA in human DRG. Importantly, functional studies demonstrated that prolonged intrathecal inhibition of aldosterone synthesis within rat DRG neurons, using an aldosterone synthase inhibitor significantly downregulated pain-associated molecules and led to sustained attenuation of inflammation-induced hyperalgesia. Together, these findings identify a conserved peripheral MR signaling axis in humans and highlight its potential as a novel target for pain modulation therapies. Full article

The intelligently thermosensitive 2-methacryloyloxyethyl phosphorylcholine (MPC) groups-conjugated methylcellulose (MC) hydrogel, abbreviated as MPC-g-MC, exhibits good potential for prevention of postoperative adhesions. However, its thermosensitive gelation mechanism and why the MPC-g-MC hydrogel shows a lower gelation temperature than that of MC hydrogel are still unclear. Molecular dynamics (MD) simulation was thus used to investigate these mechanisms in this work. After a fully atomistic MPC-g-MC molecular model was constructed, MD simulations during the thermal simulation process and at constant temperatures were performed using GROMACS 2022.3 software. The results indicated that the hydrophobic interactions between the MPC-g-MC molecular chains increased, the interactions between the MPC-g-MC molecular chains and H₂O molecules decreased with the rise in temperature, and the hydrogen bonding structures were changed during the thermal simulation process. As a result, the MPC-g-MC molecular chains began to aggregate at about 33 °C (close to the gelation temperature of 33 °C determined by the rheological measurement), bringing about the formation of the MPC-g-MC hydrogel in the macroscopic state. The mechanism of MPC-g-MC hydrogel formation showed that its lower gelation temperature than that of the MC hydrogel is attributed to the increase in the interactions (including hydrophobic interactions, hydrogen bonding interactions, Van der Waals and Coulomb forces) induced by the side MPC groups of MPC-g-MC molecules. The thermosensitive gelation mechanism revealed in this study provides an important reference for the development of novel thermosensitive MC-derived hydrogels with gelation temperatures close to human body temperature. Full article

The presence and function of the opioidergic system in sensory dorsal root ganglia (DRG) was demonstrated in various animal models of pain. To endorse recent functional and transcriptional evidence of opioid receptors in human DRG, this study compared morphological and transcriptional evidence in human and rat DRG using immunofluorescence confocal microscopy and mRNA transcript analysis. Specifically, it examined the neuronal expression of mu (MOR), delta (DOR), and kappa (KOR) opioid receptors, opioid peptide precursors (POMC, PENK, and PDYN), and key pain-signaling molecules. The results demonstrate abundant immunoreactivity in human DRG for key pain transduction receptors, including the thermosensitive ion channels TRPV1, TRPV4 and TRPA1, mechanosensitive PIEZO1 and PIEZO2, and the nociceptive-specific Nav1.8. They colocalized with calcitonin gene-related peptide (CGRP), a marker for peptidergic sensory neurons. Within this same subpopulation, we identified MOR, DOR, and KOR, while their ligand precursors were less abundant. Notably, the mRNA transcripts of MOR and PENK in human DRG were highest among the opioid-related genes; however, they were considerably lower than those of key pain-signaling molecules. These findings were corroborated by functional evidence in demonstrating the fentanyl-induced inhibition of voltage-gated calcium currents in rat DRG, which was antagonized by naloxone. The immunohistochemical and transcriptional demonstration of opioid receptors and their endogenous ligands in both human and rat DRG support recent electrophysiologic and in situ hybridization evidence in human DRG and confirms their potential as analgesic targets. This peripherally targeted approach has the advantage of mitigating central opioid-related side effects, endorsing the potential of future translational pain research from rodent models to humans. Full article

Thermosensitive biopolymer gelatin–alginate hydrogels are promising for use as dressings for wound healing and drug delivery. This work presents fluorescence arising from the internal fluorophores of alginate and gelatin biopolymers in thermosensitive hydrogels modified with calcium- and sodium-containing humic acids before and after their impregnation with the hemostatic drug aminocaproic acid. A new approach of using fluorescence emission spectra, along with the analysis of morphological features, optical properties, and the elemental composition of dried hydrogels, is used as a tool for monitoring the ability of these hydrogels for the thermosensitive delivery of a hemostatic drug. A comparative analysis made it possible to select the optimal composition of hydrogels suitable for the targeted delivery of aminocaproic acid through a gel–sol transition at physiological temperatures. Optimal concentrations of sodium-containing humic acids in gelatin–alginate hydrogels of 2.5 wt.% and 5 wt.% provided a gel–sol transition temperature of about 37 °C. The quantum yield of fluorescence of 8–10% upon introduction of 20 wt.% aminocaproic acid into these hydrogels indicates that this hemostatic drug does not destroy three-dimensional networks formed by molecules of gelatin, alginate, and humic acids, the gel–sol transition temperature for which is maintained at a physiological level without significant contracture of the wound dressing. Full article

Chitosan (CS), a versatile biopolymer obtained through the deacetylation of chitin, has gained significant interest in biomedical and pharmaceutical applications due to its biocompatibility, biodegradability, and unique gel-forming capabilities. This review comprehensively analyzes CS-based gel development, covering its extraction from various natural sources, gelation mechanisms, and biomedical applications. Different extraction methods, including chemical, biological, and green techniques, are discussed regarding efficiency and sustainability. The review explores the physicochemical properties of CS that influence its gelation behavior, highlighting various gelation mechanisms such as physical, ionic, and chemical cross-linking. Recent advances in gel formation, including Schiff base reactions, Diels–Alder click chemistry, and thermosensitive gelation, have expanded the applicability of CS hydrogels. Furthermore, CS-based gels have demonstrated potential in wound healing, tissue engineering, drug delivery, and antimicrobial applications, offering controlled drug release, enhanced biocompatibility, and tunable mechanical properties. The incorporation of nanomaterials, bioactive molecules, and functional cross-linkers has further improved hydrogel performance. The current review underscores the growing significance of CS-based gels as innovative biomaterials in regenerative medicine and pharmaceutical sciences. Full article

Phytocannabinoids (pCBs) from Cannabis sativa represent an important class of bioactive molecules, potentially useful for the treatment of a wide range of diseases. Their efficacy is due to their ability to interact with multiple targets of the endocannabinoid system, including the thermosensitive transient receptor potential (Thermo-TRPs), namely TRPV1-4, TRPA1, and TRPM8 channels. Previously, we demonstrated a shift in selectivity toward TRPA1 in the activity profile of the main pCBs, that is, CBD, ∆⁸-THC, CBG, CBC, and CBN, by swapping the pentyl chain with the α,α-dimethylheptyl (DMH) one. Using these derivatives as a starting point, here we investigate the effects on the thermo-TRPs activity profile of the integration of a quinone group into the resorcinol scaffold. We found that, while the activity on TRPA1 is substantially retained, an increase in potency/efficacy on the TRPV3 modulation is observed. Docking studies were used to elucidate the binding modes of the most active compounds toward this receptor, providing a rationale for this biological activity. In summary, we show that the quinone derivatives of DMH-pCBs are endowed with a TRPA1/TRPV3 desensitizing activity, potentially useful for the treatment of skin diseases sustained by inflammatory conditions. Full article

Background/Objectives: Chronic skin wounds (CSWs) are a worldwide healthcare problem with relevant impacts on both patients and healthcare systems. In this context, innovative treatments are needed to improve tissue repair and patient recovery and quality of life. Cord blood platelet lysate (CB-PL) holds great promise in CSW treatment thanks to its high growth factors and signal molecule content. In this work, thermo-sensitive hydrogels based on an amphiphilic poly(ether urethane) (PEU) were developed as CB-PL carriers for CSW treatment. Methods: A Poloxamer 407^®-based PEU was solubilized in aqueous medium (10 and 15% w/v) and added with CB-PL at a final concentration of 20% v/v. Hydrogels were characterized for their gelation potential, rheological properties, and swelling/dissolution behavior in a watery environment. CB-PL release was also tested, and the bioactivity of released CB-PL was evaluated through cell viability, proliferation, and migration assays. Results: PEU aqueous solutions with concentrations in the range 10–15% w/v exhibited quick (within a few minutes) sol-to-gel transition at around 30–37 °C and rheological properties modulated by the PEU concentration. Moreover, CB-PL loading within the gels did not affect the overall gel properties. Stability in aqueous media was dependent on the PEU concentration, and payload release was completed between 7 and 14 days depending on the polymer content. The CB-PL-loaded hydrogels also showed biocompatibility and released CB-PL induced keratinocyte migration and proliferation, with scratch wound recovery similar to the positive control (i.e., CB-PL alone). Conclusions: The developed hydrogels represent promising tools for CSW treatment, with tunable gelation properties and residence time and the ability to encapsulate and deliver active biomolecules with sustained and controlled kinetics. Full article

New clinical strategies for treating severe bone and cartilage injuries are required, especially for use in combination with implant procedures. For this purpose, p(VCL-co-HEMA) thermosensitive hydrogels have been activated with icariin-loaded nanoparticles to be used as bone-cell-harvesting platforms. Supercritical CO₂-SAS technology has been applied to encapsulate icariin, a small molecule that is involved in osteoblastic differentiation. Thus, physical-chemical analysis, including swelling and transmittance, showed the impact of HEMA groups in hydrogel composition. Moreover, icariin (ICA) release from p(VCL-co-HEMA) platforms, including pVCL@ICA nanoparticles, has been studied to evaluate their efficacy in relevant conditions. Finally, the thermosensitive hydrogels’ cell compatibility, transplant efficiency, and bone differentiation capacity were tested. This study identifies the optimal formulations for icariin-activated hydrogels for both control and HEMA formulations. Using this technique, osteoblastic sheets that were rich in collagen type I were successfully transplanted and recultivated, maintaining an optimal extracellular matrix (ECM) composition. These findings suggest a new cell-sheet-based therapy for bone regeneration purposes using customized and NP-activated pVCL-based cell platforms. Full article

Today a lot of attention is paid to the formation of thermosensitive systems for biomedical and industrial applications. The development of new methods for synthesis of such systems is a dynamically developing direction in chemistry and materials science. In this regard, this paper presents results of the studies of a new synthesized supramolecular polymer system based on polyethylene glycol and tetrafluoroethylene telomers. The films formed from the polymer substance have the property of switching wettability depending on temperature after heating activation. It has been established that the wettability changes at 60 °C. The contact angle of activated hydrophobic polymer film reaches 143°. Additionally, the system exhibits its properties regardless of the pH of the environment. Based on data obtained by the methods of infrared and x-ray photoelectron spectroscopy, differential thermal analysis and thermal analysis in conjunction with wettability and morphology, a model of the behavior of molecules in a polymer system was built that ensures switching of the hydrophilic/hydrophobic surface state. The resulting polymer system, as well as films based on it, can be used in targeted drug delivery, implantation surgery, as sensors, etc. Full article

It has been shown that there exist conditions under which thermosensitive copolymers of N-vinylpyrrolidone with methyl acrylate form hydrophobic–hydrophilic associations, which are unstable dynamic meshes, the bonds in which are continuously broken and created again, and the nature of the formation of such meshes depends significantly on the proportion of the hydrophobic component in the copolymer. It is shown that the interaction of the above copolymers with polyacrylic acid results in the formation of not only classical interpolymer complexes, but also hydrophilic interpolymer associates, which also represent unstable networks existing in a dynamic mode. In such meshes, the molecules of the above copolymers serve as a kind of cross-agent connecting the polyacid molecules. There are also conditions under which such meshes acquire a complex structure, since unstable bonds between macromolecular tangles of both the same and different types take part in their formation. It is shown that the transition from the formation of interpolymer complexes to the formation of hydrophilic interpolymer associates can occur, among other things, due to changes in the acidity or concentration of low-molecular salt in solution. Full article

The hard-healing chronic wounds of diabetics are still one of the most intractable problems in clinical skin injury repair. Wound microenvironments directly affect wound healing speed, but conventional dressings exhibit limited efficacy in regulating the wound microenvironment and facilitating healing. To address this serious issue, we designed a thermo-sensitive drug-controlled hydrogel with wound self-adjusting effects, consisting of a sodium alginate (SA), Antheraeapernyi silk gland protein (ASGP) and poly(N-isopropylacrylamide) (PNIPAM) for a self-adjusting microenvironment, resulting in an intelligent releasing drug which promotes skin regeneration. PNIPAM has a benign temperature-sensitive effect. The contraction, drugs and water molecules expulsion of hydrogel were generated upon surpassing lower critical solution temperatures, which made the hydrogel system have smart drug release properties. The addition of ASGP further improves the biocompatibility and endows the thermo-sensitive drug-controlled hydrogel with adhesion. Additionally, in vitro assays demonstrate that the thermo-sensitive drug-controlled hydrogels have good biocompatibility, including the ability to promote the adhesion and proliferation of human skin fibroblast cells. This work proposes an approach for smart drug-controlled hydrogels with a thermo response to promote wound healing by self-adjusting the wound microenvironment. Full article

As therapeutic agents that allow for minimally invasive administration, injectable biomaterials stand out as effective tools with tunable properties. Furthermore, hydrogels with responsive features present potential platforms for delivering therapeutics to desired sites in the body. Herein, temperature-responsive hydrogel scaffolds with embedded targeted nanoparticles were utilized to achieve controlled drug delivery via local drug administration. Poly(N-isopropylacrylamide) (pNIPAM) hydrogels, prepared with an ethylene-glycol-based cross-linker, demonstrated thermo-sensitive gelation ability upon injection into environments at body temperature. This hydrogel network was engineered to provide a slow and controlled drug release profile by being incorporated with curcumin-loaded nanoparticles bearing high encapsulation efficiency. A core (alginate)–shell (chitosan) nanoparticle design was preferred to ensure the stability of the drug molecules encapsulated in the core and to provide slower drug release. Nanoparticle-embedded hydrogels were shown to release curcumin at least four times slower compared to the free nanoparticle itself and to possess high water uptake capacity and more mechanically stable viscoelastic behavior. Moreover, this therapy has the potential to specifically address tumor tissues over-expressing folate receptors like ovaries, as the nanoparticles target the receptors by folic acid conjugation to the periphery. Together with its temperature-driven injectability, it can be concluded that this hydrogel scaffold with drug-loaded and embedded folate-targeting nanoparticles would provide effective therapy for tumor tissues accessible via minimally invasive routes and be beneficial for post-operative drug administration after tumor resection. Full article

Combretastatin derivatives is a promising class of antitumor agents, tubulin assembly inhibitors. However, due to poor solubility and insufficient selectivity to tumor cells, we believe, their therapeutic potential has not been fully realized yet. This paper describes polymeric micelles based on chitosan (a polycation that causes pH and thermosensitivity of micelles) and fatty acids (stearic, lipoic, oleic and mercaptoundecanoic), which were used as a carrier for a range of combretastatin derivatives and reference organic compounds, demonstrating otherwise impossible delivery to tumor cells, at the same time substantially reduced penetration into normal cells. Polymers containing sulfur atoms in hydrophobic tails form micelles with a zeta potential of about 30 mV, which increases to 40–45 mV when cytostatics are loaded. Polymers with tails of oleic and stearic acids form poorly charged micelles. The use of polymeric 400 nm micelles provides the dissolution of hydrophobic potential drug molecules. Micelles could significantly increase the selectivity of cytostatics against tumors, which has been shown using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, Fourier transform infrared (FTIR) spectroscopy, flow cytometry and fluorescence microscopy. Atomic force microscopy presented the difference between the unloaded micelles and those loaded with the drug: the size of the former was 30 nm on average, while the latter had a “disc-like” shape and a size of about 450 nm. The loading of drugs into the core of micelles was confirmed by UV and fluorescence spectroscopy methods; shifts of absorption and emission maxima into the long-wavelength region by tens of nm was observed. With FTIR spectroscopy, a high interaction efficiency of micelles with the drug on cells was demonstrated, but at the same time, selective absorption was observed: micellar cytostatics penetrate into A549 cancer cells 1.5–2 times better than the simple form of the drugs. Moreover, in normal HEK293T, the penetration of the drug is reduced. The proposed mechanism for reducing the accumulation of drugs in normal cells is the adsorption of micelles on the cell surface and the preservation of cytostatics to penetrate inside the cells. At the same time, in cancer cells, due to the structural features of the micelles, they penetrate inside, merging with the membrane and releasing the drug by pH- and glutathione-sensitive mechanisms. From a methodological point of view, we have proposed a powerful approach to the observation of micelles using a flow cytometer, which, in addition, allows us to quantify the cells that have absorbed/adsorbed cytostatic fluorophore and distinguish between specific and non-specific binding. Thus, we present polymeric micelles as drug delivery systems in tumors using the example of combretastatin derivatives and model fluorophore-cytostatic rhodamine 6G. Full article

Thermosensitive gels based on copolymers (PEG–chitosan, chitosan–polyethylenimine, chitosan–arginine and glycol–chitosan–spermine) are presented as promising polycations for the formation of DNA polyplexes and the potential for the development of drugs with prolonged release (up to 30 days). Being in liquid form at room temperature, such compounds can be injected into muscle tissue with rapid gel formation at human body temperature. An intramuscular depot is formed with a therapeutic agent that provides a gradual release of the drug, such as an antibacterial or cytostatic. The physico-chemical parameters of the formation of polyplexes between polycationic polymers of various compositions and molecular architecture and DNA were studied via FTIR, UV-vis and fluorescence spectroscopy using the dyes rhodamine 6G (R6G) and acridine orange (AO). The competitive displacement of AO from AO-DNA complexes showed that, with a ratio of N/P = 1, most of the DNA is bound to a polycation. During the formation of polyplexes, the DNA charge is neutralized by a polycation, which is reflected in electrophoretic immobility. The cationic polymers described in this work at a concentration of 1–4% are capable of forming gels, and the thermoreversible property is most characteristic of pegylated chitosan. BSA, as a model anionic molecule, is released by half in 5 days from the Chit5-PEG5 gel; full release is achieved in 18–20 days. At the same time, in 5 days, the gel is destroyed up to 30%, and in 20 days, by 90% (release of chitosan particles). For the first time, flow cytometry was used to study DNA polyplexes, which showed the existence of fluorescent particles in a much larger number in combination with free DNA. Thus, functional stimulus-sensitive polymers are potentially applicable for the creation of prolonged therapeutic formulations for gene delivery systems, which were obtained. The revealed regularities appear to be a platform for the design of polyplexes with controllable stability, in particular, fulfilling the requirements imposed for gene delivery vehicles. Full article