Search Results (264)

Natural products possess potent pharmacological activities and health benefits. However, drawbacks such as water insolubility, poor stability, and low bioavailability limit their practical applications. This research is dedicated to the development of suitable natural self-assembled nano-delivery systems to encapsulate natural molecule drugs, improving their dispersion and stability in aqueous solution. As a model drug, curcumin (Cur) was encapsulated in zinc–adenine nanoparticles (Zn–Adenine), based on the self-assembly of a coordination matrix material. Hyaluronic acid (HA) was further functionalized on the surface of Cur@(Zn–Adenine) to realize a tumor-targeted delivery system. The morphology was characterized through TEM and zeta potential analyses, while the encapsulation mechanism of the nanoparticles was researched via XRD and FTIR. The formed Cur@(Zn–Adenine)@HA nanoparticles exhibited good drug loading efficiency and drug loading rate. Moreover, compared to free Cur, Cur-loaded (Zn–Adenine)@HA showed enhanced pH stability and thermal stability. In particular, Cur@(Zn–Adenine)@HA demonstrated excellent biocompatibility and strong specificity for targeting CD44 protein on cancer cells. The above results indicate that (Zn–Adenine)@HA NPs can serve as an effective nano-delivery system for hydrophobic substances. Full article

The covalent conjugation of pharmaceutical compounds to polymeric carriers represents an effective strategy for enhancing drug properties, including improved bioavailability, targeted delivery, and sustained release, while reducing systemic toxicity and adverse effects. By exploiting the physicochemical characteristics of biopolymers—particularly molecular charge and weight—we engineered a polymeric platform for glucocorticoid delivery with precisely controlled parameters including particle size, surface charge, targeting capability, and release kinetics. This study reports a linker-free synthesis of hyaluronic acid-dexamethasone (HA-DEX) conjugates through Steglich esterification, catalyzed by 4-dimethylaminopyridine (DMAP), which facilitates the acylation of sterically hindered alcohols. The reaction specifically couples carboxyl groups of hyaluronic acid with the C21 hydroxyl group of dexamethasone. Incorporation of hydrophobic dexamethasone moieties induced self-assembly into nanoparticles featuring a hydrophobic core and negatively charged hydrophilic shell (−20 to −25 mV ζ-potential). In vitro characterization revealed pH-dependent release profiles, with 80–90% dexamethasone liberated in mildly acidic phosphate buffer (pH 5.2) versus 50–60% in phosphate-buffered saline (pH 7.4) over 35 days, demonstrating both sustained release and inflammation-responsive behavior. The conjugates exhibited potent anti-inflammatory activity in a human tumor necrosis factor-α (TNFα)-induced inflammation model. These findings position HA-DEX conjugates as promising candidates for targeted glucocorticoid delivery to specific anatomical sites including ocular, articular, and tympanic tissues, where their combination of CD44-targeting capability, enhanced permeability and retention effects, and stimulus-responsive release can optimize therapeutic outcomes while minimizing off-target effects. Full article

The synthesis of novel biodegradable polymers as non-viral vectors remains one of the challenging tasks in the field of gene delivery. In this study, the synthesis of the polysaccharide-g-polypeptide copolymers, namely, hyaluronic acid-g-polylysine (HA-g-PLys), using a copper-free strain-promoted azide-alkyne cycloaddition reaction was proposed. For this purpose, hyaluronic acid was modified with dibenzocyclooctyne moieties, and poly-L-lysine with a terminal azido group was obtained using ring-opening polymerization of N-carboxyanhydride of the corresponding protected amino acid, initiated with the amino group azido-PEG₃-amine. Two HA-g-PLys samples with different degrees of grafting were synthesized, and the structures of all modified and synthesized polymers were confirmed using ¹H NMR and FTIR spectroscopy. The HA-g-PLys samples obtained were able to form nanoparticles in aqueous media due to self-assembly driven by electrostatic interactions. The binding of DNA and model siRNA by copolymers to form polyplexes was analyzed using ethidium bromide, agarose gel electrophoresis, and SybrGreen I assays. The hydrodynamic diameter of polyplexes was ˂300 nm (polydispersity index, PDI ˂ 0.3). The release of a model fluorescently-labeled oligonucleotide in the complex biological medium was significantly higher in the case of HA-g-PLys as compared to that in the case of PLys-based polyplexes. In addition, the cytotoxicity in normal and cancer cells, as well as the ability of HA-g-PLys to facilitate intracellular delivery of anti-GFP siRNA to NIH-3T3/GFP+ cells, were evaluated. Full article

Global concerns about environmental pollution, poor waste management, and the rise in antimicrobial resistance due to uncontrolled antibiotic use have driven researchers to seek alternative, multifaceted solutions. Plants, animals, microorganisms, and their processing wastes serve as valuable sources of natural biopolymers and bioactive compounds. Through nanotechnology, these can be assembled into formulations with enhanced antimicrobial properties, high safety, and low toxicity. This review explores polysaccharides, including chitosan, alginate, starch, pectin, cellulose, hemicellulose, gums, carrageenan, dextran, pullulan, and hyaluronic acid, used in nanotechnology, highlighting their advantages and limitations as nanocarriers. Addressing the global urgency for alternative antimicrobials, we examined natural compounds derived from plants, microorganisms, and animals, such as phytochemicals, bacteriocins, animal antimicrobial peptides, and proteins. Focusing on their protection and retained activity, this review discusses polysaccharide-based nanoformulations with natural antimicrobials, including nanoparticles, nanoemulsions, nanocapsules, nanoplexes, and nanogels. Special emphasis is placed on strategies and formulations for the encapsulation, entrapment, and conjugation of natural compounds using polysaccharides as protective carriers and delivery systems, including a brief discussion on their future applications, prospects, and challenges in scaling up. Full article

Autoimmune diseases are driven by chronic inflammation and oxidative stress, thus requiring innovative therapeutic approaches. Polymeric nanotherapeutics incorporating antioxidant bioactive compounds offer a promising strategy for immune modulation and enhanced drug delivery. This review explores the application of polymer-based nanocarriers for improving the solubility, bioavailability, and targeted delivery of antioxidant compounds in autoimmune disease treatment. A comprehensive analysis of recent advancements in polymeric nanoformulations, including poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), chitosan, and hyaluronic acid, was conducted. The therapeutic efficacy of various antioxidant-loaded nanoparticles has been assessed in both preclinical and clinical studies. Phenolic antioxidants, such as resveratrol, curcumin, quercetin, and epigallocatechin-3-gallate, exhibit potent anti-inflammatory effects; however, their poor solubility limits their clinical application. Nanocarriers such as dendrosomes, tannic acid-based reactive oxygen species (ROS)-scavenging nanoparticles, and folic acid-functionalized systems enhance drug stability, controlled drug release, and macrophage targeting. Carotenoid and bilirubin nanoparticles further demonstrate immunomodulatory effects in multiple sclerosis, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Polymeric antioxidant nanotherapeutics provide targeted and sustained drug delivery, offering improved efficacy and reduced toxicity. Future research should focus on optimizing these nanocarriers for clinical translation and patient-centered therapeutic strategies. Full article

Acetazolamide (AZA) is a validated carbonic anhydrase inhibitor (CAI) that has the potential for use in various therapeutic applications. Herein, we report a novel AZA-loaded biodegradable nanodelivery system that was proven to enhance the antibacterial efficacy of the drug against Gram-negative bacteria, such as Escherichia coli. Carbonic anhydrases (CA, EC 4.2.1.1) in E. coli play a crucial role in bacterial metabolism and CO₂/HCO₃⁻ balance; therefore, they represent a suitable target for antimicrobial strategies. The nanoparticles were obtained using a green synthetic protocol that allowed conjugation of a natural fatty acid to hyaluronic acid (HA) under solvent-free conditions. Full characterization of the micellar aggregates was performed (diameter of the micelles, zeta potential, and drug release study). In vitro studies demonstrated that AZA loaded in HA-based nanoparticles significantly inhibited E. coli growth at concentrations as low as 0.5 µg/mL, whereas higher concentrations of free AZA were required, as previously reported. Additionally, encapsulated AZA disrupted glucose consumption in E. coli, indicating its profound impact on bacterial metabolism. These findings suggest that the HA–palmitate nanoparticle not only enhances the delivery and efficacy of AZA but also offers a strategy to affect bacterial metabolism. Full article

Objectives: This study aimed to develop and evaluate nanostructured lipid carriers (NLCs) loaded with meloxicam (Melox) and a therapeutic antibacterial and anti-inflammatory liquid lipid, clove oil (CO) for periodontitis treatment, a complex inflammatory condition necessitating advanced drug delivery systems. The NLC–Melox formulation was integrated into three hydrogels, hypromellose (HPMC), zinc hyaluronate (ZnHA), and sodium hyaluronate (NaHA), to conduct a comparative analysis focusing on enhanced localized drug delivery, improved mucoadhesion, prolonged retention, and significant therapeutic outcomes. Methods: NLC–Melox was prepared by homogenization and characterized by dynamic light scattering (DLS). Subsequently, NLC–Melox-loaded gels were subjected to transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Raman spectroscopy, and rheological analysis. In vitro drug release, anti-inflammatory activity (BSA denaturation assay), and antibacterial efficacy (MIC, MBC) were investigated to assess therapeutic potential. Results: DLS revealed a particle size of 183 nm with a polydispersity index of 0.26, indicating homogeneity. TEM confirmed consistent morphology and uniform nanoparticle distribution. DSC and XRD demonstrated the amorphous nature of Melox, enhancing solubility and stability. Spectroscopy confirmed no chemical interactions between components. Rheological studies identified ZnHA as the most mucoadhesive and structurally stable gel. In vitro release studies showed sustained drug release over 24 h. Melox and CO-loaded formulations demonstrated significant anti-inflammatory activity and notable antibacterial efficacy due to the antibacterial oil. Conclusions: The study highlighted the potential of NLC-based mucoadhesive hydrogels as an effective strategy for periodontitis treatment. The formulation offered improved drug solubility, therapeutic efficacy, mucoadhesivity, and prolonged delivery, making it a promising candidate for localized therapy. Full article

Background/Objectives: Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages promotes chronic inflammation, oxidative stress, delayed healing, and alveolar bone resorption. Resveratrol (RSV), a polyphenol with antioxidant, anti-inflammatory, and pro-osteogenic properties, holds potential to restore macrophage balance. However, its clinical application is limited by poor bioavailability and instability. This study aimed to develop and evaluate a novel RSV delivery system to overcome these limitations and promote periodontal tissue regeneration under diabetic conditions. Methods: A drug delivery system comprising RSV-loaded solid lipid nanoparticles embedded within a cross-linked hyaluronic acid hydrogel (RSV@CLgel) was formulated. The system was tested under hyperglycemic and inflammatory conditions for its effects on macrophage polarization, cytokine expression, oxidative stress, mitochondrial function, and osteoblast differentiation. Results: RSV@CLgel effectively suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while upregulating anti-inflammatory markers (IL-10, TGF-β). It significantly reduced oxidative stress by decreasing ROS and lipid peroxidation levels and improved mitochondrial function and antioxidant enzyme activity. Furthermore, RSV@CLgel enhanced osteoblast differentiation, as evidenced by increased ALP activity, calcium nodule formation, and upregulation of osteogenic genes (COL-I, RUNX2, OCN, OPN). It also inhibited RANKL-induced osteoclastogenesis, contributing to alveolar bone preservation. Conclusions: The RSV@CLgel delivery system presents a promising multifunctional strategy for the management of diabetic periodontitis. By modulating immune responses, reducing oxidative stress, and promoting periodontal tissue regeneration, RSV@CLgel addresses key pathological aspects of diabetes-associated periodontal disease. Full article

Hyaluronic acid (HA) is a linear, unbranched polysaccharide classified as a glycosaminoglycan. While HA is found in various tissues throughout the body, over half of its total proportion is found in the skin. The role of HA in the skin is complex and multifaceted. HA maintains proper hydration, elasticity, and skin firmness, serving as a key extracellular matrix (ECM) component. With age, HA production gradually decreases, leading to reduced water-binding capacity, drier and less elastic skin, and the formation of wrinkles. Additionally, HA plays an active role in the wound-healing process at every stage. This review summarizes the current background knowledge about the role of HA in skin aging and wound healing. We discuss the latest applications of HA in aging prevention, including anti-aging formulations, nutricosmetics, microneedles, nanoparticles, HA-based fillers, and skin biostimulators. Furthermore, we explore various HA-based dressings used in wound treatment, such as hydrogels, sponges, membranes, and films. Full article

The effectiveness of iron oxide nanoparticles in enhancing crop plant development depends on their stabilization. In this study, the effect of hyaluronic acid (HA), used both as a stabilizer for iron oxide nanoparticles (HA-MNP) and independently, was evaluated in maize seedlings. Different concentrations of HA-MNP (0.625–7.5 mg/L) were tested alongside a 0.01% HA solution. Growth parameters, antioxidant enzyme activities (peroxidase and polyphenol oxidase), photosynthetic pigments (chlorophyll and carotenoids), phenolic content, and genotoxicity were analyzed. While HA alone led to slight decreases in seedling length, pigment content, and polyphenol levels compared to the control, it increased peroxidase activity and mitotic index. Lower concentrations of HA-MNP (below 2.5 mg/L) enhanced seedling growth, likely due to improved iron uptake, whereas higher concentrations reduced pigment and phenolic content. All HA-MNP concentrations induced genotoxic effects, which was proven by an increased mitotic index and chromosomal aberrations, indicating both positive and defensive plant responses to oxidative stress. These findings suggest a complex interaction between HA, HA-MNP, and maize seedlings, where HA concentrations play a significant role in modulating growth and stress response, while higher concentrations may induce toxicity. Full article

Rare earth metal nanoparticles, some of which are already widely used in medicine, are of growing interest in the modern scientific community. One of the promising rare earth metals for biomedical applications is cerium, specifically its oxide form, which is characterized by a higher level of stability and safety. According to a number of studies, cerium dioxide has a wide range of biological effects (regenerative, antimicrobial, antioxidant, antitumor), which justifies the interest of its potential application in medicine. However, these effects and their intensity vary significantly across a number of studies. Since cerium dioxide was used in these studies, it can be assumed that not only is the chemical formula important, but also the physicochemical parameters of the nanoparticles obtained, and consequently the methods of their synthesis and modification with the use of excipients. In this review, we considered the possibilities of using a number of excipients (polyacrylate, polyvinylpyrrolidone, dextran, hyaluronic acid, chitosan, polycarboxylic acids, lecithin, phosphatidylcholine) in the context of preserving the biological effects of cerium dioxide and its physicochemical properties, as well as the degree of study of these combinations from the point of view of the prospect of creating drugs based on it for biomedical applications. Full article

The prevalence of bacterial infections in wounds is a significant challenge to successful wound healing. This study investigates the antibacterial effect of hyaluronic acid and alginate aerogel loaded with zinc oxide nanoparticles as a potential dressing for wound healing. The aerogel composite was synthesized via supercritical gel drying and characterized by scanning electron microscope, Fourier transform infrared spectroscopy, and nitrogen porosimetry. The absorptivity of the prepared aerogel was evaluated, as well as the antibacterial activity, which was evaluated against common wound pathogens, including Staphylococcus aureus and Escherichia coli, using the agar diffusion method. The results show the effective antibacterial properties of the prepared hydrogel and aerogel. Furthermore, the results show water absorption ability of 5791 and 1585% for loaded and unloaded aerogels, respectively. The ZnO released from the aerogel exhibited a rapid release followed by a slow and sustained release. These findings highlight the potential of aerogels based on hyaluronic acid and alginate and loaded with zinc oxide nanoparticles as an innovative antibacterial wound dressing material, which is expected to improve wound healing and reduce the risk of bacterial infections. Full article

Lidocaine plays a significant role in postoperative analgesia by effectively reducing pain. However, due to its short half-life, it is challenging for lidocaine to achieve the desired duration of analgesia in clinical settings. Drug delivery systems can regulate the release rate over time, making them one of the most effective strategies for achieving sustained release. In this work, a multi-level drug delivery system was designed using hyaluronic acid-modified zeolitic imidazolate framework-8 (HA/ZIF-8) nanoparticles and injectable hydrogels composed of modified natural polymers. Lidocaine was incorporating into the modified ZIF-8 and uniformly dispersed within the hydrogel network. The dynamic light scattering (DLS) and Fourier transform infrared spectrometer (FTIR) results indicate the successful loading of lidocaine into ZIF-8, while the X-ray diffractometer (XRD) results confirm that the loading of lidocaine did not disrupt the crystal structure of ZIF-8. The coating of hyaluronic acid on ZIF-8 enhanced cell biocompatibility, with cell viability increasing by 89% at the same concentration. This multi-level drug delivery system can be injected through a 27-guage needle. In vitro release studies demonstrated a sustained release of lidocaine for more than 4 days and kinetic simulations aligned with the Bshakar model, indicating its potential for use in long-acting analgesic preparations. Full article

Hyaluronic acid (HA)-based hydrogels offer a promising approach for soft tissue application due to their biocompatibility, tunable mechanical properties, ability to mimic the extracellular matrix, and capacity to support cell adhesion and proliferation. In this work, bioadhesive composite hydrogels were developed by integrating graphite derivatives (EG) into a dopamine-modified HA matrix (HA-Cat), which enhances tissue adhesion through catechol groups that mimic mussel-inspired adhesion mechanisms. The EG was functionalized via 1,3-dipolar cycloaddition reaction (f-EG), that allowed the anchoring of silver nanoparticles (f-EG-Ag) and grafting of hydrocaffeic acid (f-EG-Cat) on the functionalized EG surfaces. The hydrogels were produced by oxidative crosslinking of HA-Cat under mild basic pH conditions using sodium periodate. Indirect in vitro assays using L929 fibroblast cells showed high biocompatibility and enhanced cell proliferation at optimized composite hydrogel concentrations. These findings suggest that composite hydrogels could find an application as bioactive, adhesive scaffolds for the regeneration of soft tissues, where they can facilitate localized agent delivery and integration with the host tissue. Full article

Background/Objectives: Fungal infections caused by Candida species remain a significant clinical challenge, exacerbated by limitations in current antifungal therapies, including toxicity and poor bioavailability. This study aimed to develop and evaluate voriconazole-loaded zein–pectin–hyaluronic acid nanoparticles (ZPHA-VRC NPs) as a novel drug delivery system to enhance efficacy and reduce toxicity. Alternative in vitro and in vivo models were utilized to assess the safety and therapeutic potential of the nanoparticles. Methods: ZPHA-VRC NPs were prepared using a nanoprecipitation method and characterized for particle size, polydispersity index, zeta potential, and encapsulation efficiency. Antifungal activity was assessed via MIC assays against Candida albicans, C. krusei, and C. parapsilosis. Cytotoxicity was evaluated on Vero cells, while in vivo toxicity and efficacy were assessed using Galleria mellonella and Caenorhabditis elegans models. The therapeutic efficacy was further evaluated in an infected Caenorhabditis elegans model using survival and health scores. Results: ZPHA-VRC nanoparticles exhibited favorable physicochemical properties, including a particle size of approximately 192 nm, a polydispersity index of 0.079, a zeta potential of −24 mV, and an encapsulation efficiency of 34%. The nanoparticles retained antifungal activity comparable to free voriconazole while significantly reducing cytotoxicity. In vivo studies using G. mellonella and C. elegans demonstrated that ZPHA-VRC NPs markedly improved survival rates, reduced fungal burden, and enhanced health scores in infected models, outperforming the free drug. Additionally, the nanoparticles exhibited a superior safety profile, minimizing systemic toxicity while maintaining therapeutic efficacy. Conclusions: ZPHA-VRC NPs offer a safer and more effective delivery system for VRC, addressing the limitations of conventional formulations. The integration of alternative efficacy and safety models highlights their value in preclinical research. Full article