Polysaccharides like hyaluronan (HA) and chondroitin sulfate (CS) are native of the brain's extracellular matrix crucial for myelination and brain maturation. Despite extensive research on HA and CS as drug delivery systems (DDS), their high water solubility limits their application as drug carriers. This study introduces an injectable DDS using aldehyde-modified hyaluronic acid (HAOX) hydrogel containing polyelectrolyte complexes (PEC) formed with calcium, gelatin, and either CS or aldehyde-modified CS (CSOX) to deliver minocycline for Multiple Sclerosis therapy. PECs with CSOX enable covalent crosslinking to HAOX, creating immobilized PECs (HAOX_PECOX), while those with CS remain unbound (HAOX_PECS). The in situ forming DDS can be administered via a 20 G needle, with rapid gelation preventing premature leakage. The system integrates into an implanted device for minocycline release through either Fickian or anomalous diffusion, depending on PEC immobilization. HAOX_PECOX reduced burst release by 88 %, with a duration of 127 h for 50 % release. The DDS exhibited an elastic modulus of 3800 Pa and a low swelling ratio (0-1 %), enabling precise control of minocycline release kinetics. Released minocycline reduced IL-6 secretion in the Whole Blood Monocytes Activation Test, suggesting that DDS formation may not alter the biological activity of the loaded drug.
- MeSH
- aldehydy chemie MeSH
- chondroitin sulfáty * chemie MeSH
- hydrogely * chemie farmakologie MeSH
- interleukin-6 metabolismus MeSH
- kyselina hyaluronová * chemie MeSH
- lidé MeSH
- minocyklin * chemie farmakologie aplikace a dávkování MeSH
- nosiče léků * chemie MeSH
- polyelektrolyty * chemie MeSH
- systémy cílené aplikace léků metody MeSH
- uvolňování léčiv MeSH
- želatina * chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Hyaluronan, a linear glycosaminoglycan comprising D-N-acetylglucosamine and D-glucuronic acid, is the main component of the extracellular matrix. Its influence on cell proliferation, migration, inflammation, signalling, and other functions, depends heavily on its molecular weight and chemical modification. Unsaturated HA oligosaccharides are available in defined length and purity. Their potential therapeutic utility can be further improved by chemical modification, e. g., reduction. No synthesis of such modified oligosaccharides, either stepwise or by hyaluronan cleavage, has been reported yet. Here we show a three-step synthesis (esterification, depolymerization and reduction) of unsaturated even numbered hyaluronan oligosaccharides with carboxylates and the reducing terminus reduced to an alcohol. Particular oligosaccharides were synthesised. The modified oligosaccharides are not cleaved by mammalian or bacterial hyaluronidase and do not affect the growth of mouse and human fibroblasts. Further, MTT and NRU viability tests showed that they inhibit the growth of human colon carcinoma cells HT-29 by 20-50 % in concentrations 500-1000 μg/mL. Interestingly, this effect takes place regardless of CD44 receptor expression and was not observed with unmodified HA oligosaccharides. These compounds could serve as enzymatically stable building blocks for biologically active substances.
- MeSH
- antigeny CD44 metabolismus MeSH
- buňky HT-29 MeSH
- cytostatické látky * farmakologie chemie chemická syntéza MeSH
- fibroblasty účinky léků MeSH
- hyaluronoglukosaminidasa * metabolismus antagonisté a inhibitory MeSH
- kyselina hyaluronová * chemie farmakologie MeSH
- lidé MeSH
- myši MeSH
- oligosacharidy * chemie farmakologie MeSH
- proliferace buněk * účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In the realm of surgical and dental applications, hyaluronic acid (HA) braided threads show significant therapeutic potential due to their incorporation of pharmaceutical active ingredients. This study primarily focuses on resolving the crucial challenge of devising a deposition method that can ensure both precision and uniformity in the content of the active ingredient Octenidine dihydrochloride (OCT) within each segment of the threads. Our objective in this study was to develop a continuous deposition method for OCT onto a braided thread composed of 24 hyaluronic acid-based fibers, aiming for a specific OCT content of 0.125 μg/mm, while maintaining a maximum allowable deviation of ±15% in OCT content. The motivation behind designing this novel method stemmed from the necessity of employing a volatile solvent for the active agent. Conventional wetting methods proved unsuitable due to fluctuations in the solution's concentration during deposition, and alternative methods known to us demanded intricate technical implementations. The newly introduced method offers distinct advantages, including its online processing speed, scalability potential, and cost-efficiency of the active agent solution. Additionally, it minimizes the impact on the natural polymer thread, preserving energy by obviating the need for complete thread saturation. Our research and precise apparatus development resulted in achieving the desired thread properties, with an OCT content of (1.51 ± 0.09) μg per 12 mm thread piece. These findings not only validate the suitability of this innovative method for depositing active agents but also extend its potential applicability beyond dental care.
- Publikační typ
- časopisecké články MeSH
The negative impact of cigarette smoking on the skin includes accelerated aging, pigmentation disorders, and impaired wound healing, but its effect on the skin barrier is not completely understood. Here, we studied the changes in selected epidermal proteins and lipids between smokers (45-66 years, smoking > 10 years, > 10 cigarettes per day) and non-smokers. Volar forearm epidermal and stratum corneum samples, obtained by suction blister and tape stripping, respectively, showed increased thickness in smokers. In the epidermis of smokers, we observed a significant upregulation of filaggrin, loricrin, and a trend of increased involucrin but no differences were found in the case of transglutaminase 1 and kallikrein-related peptidase 7, on the gene and protein levels. No significant changes were observed in the major skin barrier lipids, except for increased cholesterol sulfate in smokers. Liquid chromatography coupled with mass spectrometry revealed shorter acyl chains in ceramides, and an increased proportion of sphingosine and 6-hydroxysphingosine ceramides (with C4 trans-double bond) over dihydrosphingosine and phytosphingosine ceramides in smokers, suggesting altered desaturase 1 activity. Smokers had more ordered lipid chains found by infrared spectroscopy. In conclusion, cigarette smoking perturbs the homeostasis of the barrier proteins and lipids even at a site not directly exposed to smoke.
New studies have shown the great potential of the combination of in situ enzymatically cross-linked hydrogels based on tyramine derivative of hyaluronic acid (HA-TA) with platelet-rich plasma (PRP) and platelet lysate in regenerative medicine. This study describes how the presence of PRP and platelet lysate affects the kinetics of gelation, viscoelastic properties, swelling ratio, and the network structure of HA-TA hydrogels and how the encapsulation of PRP in hydrogels affects the bioactivity of released PRP determined as the ability to induce cell proliferation. The properties of hydrogels were tuned by a degree of substitution and concentration of HA-TA derivatives. The addition of platelet derivatives to the reaction mixture slowed down the cross-linking reaction and reduced elastic modulus (G') and thus cross-linking efficiency. However, low-swellable hydrogels (7-190%) suitable for soft tissue engineering with G' 200-1800 Pa were prepared with a gelation time within 1 min. It was confirmed that tested cross-linking reaction conditions are suitable for PRP incorporation because the total bioactivity level of PRP released from HA-TA hydrogels was ≥87% and HA-TA content in the hydrogels and thus mesh size (285-482 nm) has no significant effect on the bioactivity level of released PRP.
Osteoarthritisis a highly prevalent musculoskeletal disorder characterized by degradation of cartilage and synovial fluid (SF). Platelet derivatives as platelet-rich plasma (PRP) and platelet lysate have great potential in the treatment of osteoarthritis because they contain biologically active substances including growth factors (GFs). Rapid release of GFs and their short biological half-life are factors that can limit the therapeutic impact of PRP therapy. Herein, the first work that describes hydrogels based on polyaldehyde derivative of hyaluronic acid (HA-OX) as carriers of platelet derivatives for in situ applications is presented, which can be a possible solution to the problem. HA-OX hydrogels containing 50% (w/w) of PRP or platelet lysate can be injected using a syringe due to low viscosity(<10 Pa s) and injection force (<20 N), and reach elastic modulus up to 2000 Pa. Insulin-like GF-1 and Platelet-derived GF-AB release from HA-OX hydrogels (mesh size 297-406 nm) by Fickian and non-Fickian diffusion respectively. The released PRP GFs maintain their ability to induce cell proliferation (87%-92%). Based on the obtained results, the unique concept of a new material that can restore viscoelastic properties of SF and at the same time gradually deliver GFs from platelet derivatives is designed.
Nanofibrous materials are used in drug delivery as carriers of active ingredients. These can be incorporated into the materials with various electrospinning methods that differ mainly in the way spinning solutions are prepared. Each method affects primarily the encapsulation efficiency and distribution of active ingredients in the materials. This study focuses on the incorporation of octenidine dihydrochloride (OCT) and triclosan (TRI) into nanofibrous materials electrospun from native hyaluronic acid emulsions, dispersions, and blends. OCT had no substantial effect on fiber morphology, which is affected by the solvent system. All OCT encapsulation efficiencies were comparable (approximately 90%). TRI encapsulation efficiencies varied greatly depending on the method used. Merely 3% of TRI was encapsulated when it was spun from a dispersion. Encapsulation efficiency was higher, and TRI was incorporated in clusters when an emulsion was used. The best result was achieved with a blend, in which case 96% of TRI was encapsulated.
- MeSH
- antiinfekční látky lokální chemie MeSH
- emulze chemie MeSH
- kyselina hyaluronová chemie MeSH
- nanovlákna chemie MeSH
- Publikační typ
- časopisecké články MeSH
Photoaged skin exhibits signs of inflammation, DNA damage and changes in morphology that are visible at the macroscopic and microscopic levels. Photoaging also affects the extracellular matrix (ECM) including hyaluronan (HA), the main polysaccharide component thereof. HA is a structurally simple but biologically complex molecule that serves as a water-retaining component and provides both a scaffold for a number of the proteins of the ECM and the ligand for cellular receptors. The study provides an overview of the literature concerning the changes in HA amount, size and metabolism, and the potential role of HA in photoaging. We also suggest novel HA contributions to photoaging based on our knowledge of the role of HA in other pathological processes, including the senescence and inflammation-triggered ECM reorganization. Moreover, we discuss potential direct or indirect intervention to mitigate photoaging that targets the hyaluronan metabolism, as well as supplementation.
This work reveals the growing potential of novel electrochemical methods that are applicable for polysaccharides. It was shown for the first time that the molecules of hyaluronic acid (HA) exhibit electrochemical response using phase-sensitive alternating current (AC) voltammetry in phase-out mode. Adsorption and desorption processes of HA fragments at a charged interface of mercury electrode were observed in buffered HA solutions. Electrostatic and hydrophobic manners of interactions were distinguished for native hyaluronan fragments in a wide electric potential range. The AC voltammetry response depended on the temperature, concentration, and length of HA chains. Results of this work open possibilities for further structural characterization of widely used HA fragments and understanding manners of interactions with charged hydrophobic surfaces that could be useful in the future for understanding HA interactions at biological levels.
- Publikační typ
- časopisecké články MeSH
Nanofibrous materials produced from natural polymers have wide range of potential uses in regenerative medicine. This paper focuses on preparation of nanofibrous layers produced from intentionally hydrophobized derivatives of hyaluronan, which is known for its ability to promote wound healing. This structural modification of hyaluronan expands the range of potential uses of this promising material, which is otherwise limited due to the hydrophilic nature of hyaluronic acid. The aim of this research was preparation of nanofibrous material that would retain its fibrous structure and dimensional stability even after getting into contact with an aqueous medium, which is impossible to achieve with layers composed solely of native hyaluronan. As a result, such material would be able to retain its breathability and good mechanical properties when both dry and wet. Furthermore, all prepared materials were proved non-toxic for cells. This self-supporting nanofibrous matrix can be used as a scaffold, or porous wound dressing.
- Publikační typ
- časopisecké články MeSH
