RESUMO
Bovine serum albumin (BSA) hydrogels are non-immunogenic, low-cost, biocompatible, and biodegradable. In order to avoid toxic cross-linking agents, gellan was oxidized with NaIO4 to obtain new functional groups like dialdehydes for protein-based hydrogel cross-linking. The formed dialdehyde groups were highlighted with FT-IR and NMR spectroscopy. This paper aims to investigate hydrogel films for biomedical applications obtained by cross-linking BSA with oxidized gellan (OxG) containing immobilized ß-cyclodextrin-curcumin inclusion complex (ß-CD-Curc) The ß-CD-Curc improved the bioavailability and solubility of Curc and was prepared at a molar ratio of 2:1. The film's structure and morphology were evaluated using FT-IR spectroscopy and SEM. The swelling degree (Q%) values of hydrogel films depend on hydrophilicity and pH, with higher values at pH = 7.4. Additionally, the conversion index of -NH2 groups into Schiff bases increases with an increase in OxG amount. The polymeric matrix provides protection for Curc, is non-cytotoxic, and enhances antioxidant activity. At pH = 5.5, the skin permeability and release efficiency of encapsulated curcumin were higher than at pH = 7.4 because of the interaction of free aldehyde and carboxylic groups from hydrogels with amine groups from proteins present in the skin membrane, resulting in a better film adhesion and more efficient curcumin release.
RESUMO
The sole effective treatment for most patients with heart valve disease is valve replacement by implantation of mechanical or biological prostheses. However, mechanical valves represent high risk of thromboembolism, and biological prostheses are prone to early degeneration. In this work, we aim to determine the potential of novel environmentally-friendly non-isocyanate polyurethanes (NIPUs) for manufacturing synthetic prosthetic heart valves. Polyhydroxyurethane (PHU) NIPUs are synthesized via an isocyanate-free route, tested in vitro, and used to produce aortic valves. PHU elastomers reinforced with a polyester mesh show mechanical properties similar to native valve leaflets. These NIPUs do not cause hemolysis. Interestingly, both platelet adhesion and contact activation-induced coagulation are strongly reduced on NIPU surfaces, indicating low thrombogenicity. Fibroblasts and endothelial cells maintain normal growth and shape after indirect contact with NIPUs. Fluid-structure interaction (FSI) allows modeling of the ideal valve design, with minimal shear stress on the leaflets. Injection-molded valves are tested in a pulse duplicator and show ISO-compliant hydrodynamic performance, comparable to clinically-used bioprostheses. Poly(tetrahydrofuran) (PTHF)-NIPU patches do not show any evidence of calcification over a period of 8 weeks. NIPUs are promising sustainable biomaterials for the manufacturing of improved prosthetic valves with low thrombogenicity.
Assuntos
Próteses Valvulares Cardíacas , Poliuretanos , Humanos , Poliuretanos/química , Isocianatos , Células Endoteliais , Valva Aórtica/cirurgiaRESUMO
Polyurethanes (PUs) have adjustable mechanical properties, making them suitable for a wide range of applications, including in the biomedical field. Historically, these PUs have been synthesized from isocyanates, which are toxic compounds to handle. This has encouraged the search for safer and more environmentally friendly synthetic routes, leading today to the production of nonisocyanate polyurethanes (NIPUs). Among these NIPUs, polyhydroxyurethanes (PHUs) bear additional hydroxyl groups, which are particularly attractive for derivatizing and adjusting their physicochemical properties. In this paper, polyether-based NIPU elastomers with variable stiffness are designed by functionalizing the hydroxyl groups of a poly(propylene glycol)-PHU by a cyclic carbonate carrying a pendant unsaturation, enabling them to be post-photo-cross-linked with polythiols (thiol-ene). Elastomers with remarkable mechanical properties whose stiffness can be adjusted are obtained. Thanks to the unique viscous properties of these PHU derivatives and their short gel times observed by rheology experiments, formulations for light-based three-dimensional (3D) printing have been developed. Objects were 3D-printed by digital light processing with a resolution down to the micrometer scale, demonstrating their ability to target various designs of prime importance for personalized medicine. In vitro biocompatibility tests have confirmed the noncytotoxicity of these materials for human fibroblasts. In vitro hemocompatibility tests have revealed that they do not induce hemolytic effects, they do not increase platelet adhesion, nor activate coagulation, demonstrating their potential for future applications in the cardiovascular field.
Assuntos
Elastômeros , Poliuretanos , Humanos , Poliuretanos/farmacologia , Poliuretanos/química , Elastômeros/química , Isocianatos/química , Próteses e Implantes , SupuraçãoRESUMO
Surface modification of lipid nanocapsules (LNC) is necessary to impart stealth properties to these drug carriers and enhance their accumulation into the tumor microenvironment. While pegylation is commonly used to prolong the circulation time of LNC, the increased presence of anti-PEG antibodies in the human population and the internalization issues associated to the PEG shell are strong incentives to search alternatives. This work describes the development of amphiphilic poly(N-vinyl amide)-based (co)polymers, including pH-responsive ones, and their use as LNC modifiers towards improved drug delivery systems. RAFT polymerization gave access to a series of LNC modifiers composed of poly(N-methyl-N-vinyl acetamide), poly(N-vinyl pyrrolidone) or pH-responsive vinylimidazole-based sequence bearing a variety of lipophilic end-groups, namely octadecyl, dioctadecyl or phospholipid groups, for anchoring to the LNC. Decoration of the LNC with these families of poly(N-vinyl amide) derivatives was achieved via both post-insertion and per-formulation methods. This offered valuable and non-toxic LNC protection from opsonization by complement activation, emphasized the benefit of dioctadecyl in the per-formulation approach and highlighted the great potential of poly(N-methyl-N-vinyl acetamide) as PEG alternative. Moreover, incorporation of imidazole moieties in the shell of the carrier imparted pH-responsiveness to the LNC likely to increase the cellular uptake in the acidic tumor microenvironment, opening up new possibilities in the field of active targeting.