In situ formed aldehyde-modified hyaluronic acid hydrogel with polyelectrolyte complexes of aldehyde-modified chondroitin sulfate and gelatin: An approach for minocycline delivery.

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.

Enzymatically stable unsaturated hyaluronan-derived oligosaccharides with selective cytostatic properties.

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.

Trends in the Incorporation of Antiseptics into Natural Polymer-Based Nanofibrous Mats.

Nanofibrous materials represent a very promising form of advanced carrier systems that can be used industrially, especially in regenerative medicine as highly functional bandages, or advanced wound dressings. By incorporation of antimicrobial additives directly into the structure of the nanofiber carrier, the functionality of the layer is upgraded, depending on the final requirement-bactericidal, bacteriostatic, antiseptic, or a generally antimicrobial effect. Such highly functional nanofibrous layers can be prepared mostly by electrospinning technology from both synthetic and natural polymers. The presence of a natural polymer in the composition is very advantageous. Especially in medical applications where, due to the presence of the material close to the human body, the healing process is more efficient and without the occurrence of an unwanted inflammatory response. However, converting natural polymers into nanofibrous form, with a homogeneously distributed and stable additive, is a great challenge. Thus, a combination of natural and synthetic materials is often used. This review clearly summarizes the issue of the incorporation and effectiveness of different types of antimicrobial substances, such as nanoparticles, antibiotics, common antiseptics, or substances of natural origin, into electrospun nanofibrous layers made of mostly natural polymer materials. A section describing the problematic aspects of antimicrobial polymers is also included.