ABSTRACT
Vascular diseases are among the primary causes of death worldwide. In serious conditions, replacement of the damaged vessel is required. Autologous grafts are preferred, but their limited availability and difficulty of the harvesting procedures favour synthetic alternatives' use. However, as synthetic grafts may present significant drawbacks, tissue engineering-based solutions are proposed. Herein, tubular hydrogels of alginate combined with collagen type I and/or silk fibroin were prepared by ionotropic gelation using gelatin hydrogel sacrificial moulds loaded with calcium ions (Ca2+). The time of exposure of alginate solutions to Ca2+-loaded gelatin was used to control the wall thickness of the hydrogels (0.47 ± 0.10 mm-1.41 ± 0.21 mm). A second crosslinking step with barium chloride prevented their degradation for a 14 day period and improved mechanical properties by two-fold. Protein leaching tests showed that collagen type I, unlike silk fibroin, was strongly incorporated in the hydrogels. The presence of silk fibroin in the alginate matrix, containing or not collagen, did not significantly improve hydrogels' properties. Conversely, hydrogels enriched only with collagen were able to better support EA.hy926 and MRC-5 cells' growth and characteristic phenotype. These results suggest that a two-step crosslinking procedure combined with the use of collagen type I allow for producing freestanding vascular substitutes with tuneable properties in terms of size, shape and wall thickness.
Subject(s)
Fibroins , Hydrogels , Alginates , Collagen , Collagen Type I , GelatinABSTRACT
Solid inclusion complex between hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and minoxidil (MXD) was prepared by freeze-drying and characterized by yield, drug loading and dissolution rate. Moreover, the complex was formulated as alginate gel (GEL HP-ß-CD)/MXD 3.5% w/w). The efficacy of the novel GEL HP-ß-CD)/MXD 3.5% w/w and of MXD 3.5% w/w ethanolic/propylene-glycol solution (MXD solution) were evaluated by monitoring the hair growth of dorsal skin 1-4 weeks after depilation followed by histological analysis and gene expression in skin biopsies in male rat. Patch-clamp experiments and cell-dehydrogenase activity (CDA) were performed to evaluate the capability of the formulations to activate "in vitro" the ATP-sensitive K+-channels (KATP) and their effects on cell viability in skin fibroblasts. After 3 weeks, the MXD solution and MXD/HP-ß-CD GEL enhanced the hair growth, respectively, of 80.1⯱â¯2% and 84.3⯱â¯4% vs controls. After 4 weeks, the MXD/HP-ß-CD GEL significantly enhanced the hair length and bulb diameter vs others groups. The MXD/HP-ß-CD GEL significantly enhanced the mRNA levels of the SUR2 and Kir6.1 subunits of the KATP channels and AKT2 vs other groups. The AR gene was down-regulated vs controls following the treatment with either MXD formulations. Either MXD (10-4â¯M) formulations were effective in potentiating the KATP currents. The MXD solution and its vehicle after 9â¯h of incubation time, but not MXD/HP-ß-CD, reduced CDA in fibroblasts. In sum, the MXD/HP-ß-CD GEL shows a favorable profile following topical long-term use.
Subject(s)
2-Hydroxypropyl-beta-cyclodextrin/pharmacology , Alginates/pharmacology , Alopecia/drug therapy , Gels/pharmacology , Minoxidil/pharmacology , 2-Hydroxypropyl-beta-cyclodextrin/chemistry , Administration, Topical , Alginates/chemistry , Alopecia/metabolism , Animals , Chemistry, Pharmaceutical/methods , Drug Carriers/chemistry , Excipients/chemistry , Fibroblasts/drug effects , Gels/chemistry , Glucuronic Acid/chemistry , Glucuronic Acid/pharmacology , Hair/drug effects , Hair/metabolism , Hexuronic Acids/chemistry , Hexuronic Acids/pharmacology , KATP Channels/metabolism , Male , Minoxidil/chemistry , Rats , Rats, Wistar , Skin/metabolism , Skin Absorption/drug effects , Solubility/drug effects , Water/chemistryABSTRACT
In this paper, both maghemite (γ-Fe2O3) and titanium oxide (TiO2) nanoparticles were synthesized and mixed in various ratios and embedded in PVA and alginate beads. Batch sorption experiments were applied for removal of barium ions from aqueous solution under sunlight using the beads. The process has been investigated as a function of pH, contact time, temperature, initial barium ion concentration and TiO2:γ-Fe2O3 ratios (1:10, 1:60 and 1). The recycling attributes of these beads were also considered. Furthermore, the results revealed that 99% of the Ba(II) was eliminated in 150min at pH 8 under sunlight. Also, the maghemite and titania PVA-alginate beads can be readily isolated from the aqueous solution after the process and reused for at least 7 times without significant losses of their initial properties. The reduction of Ba(II) with maghemite and titania PVA-alginate beads fitted the pseudo first order and second order Langmuir-Hinshelwood (L-H) kinetic model.