Injectable hybrid hydrogels physically crosslinked based on carrageenan and green graphene for tissue repair.

Injectable and biocompatible novel hybrid hydrogels based on physically crosslinked natural biopolymers and green graphene for potential use in tissue engineering are reported. Kappa and iota carrageenan, locust bean gum and gelatin are used as biopolymeric matrix. The effect of green graphene content on the swelling behavior, mechanical properties and biocompatibility of the hybrid hydrogels is investigated. The hybrid hydrogels present a porous network with three-dimensionally interconnected microstructures, with lower pore size than that of the hydrogel without graphene. The addition of graphene into the biopolymeric network improves the stability and the mechanical properties of the hydrogels in phosphate buffer saline solution at 37 °C without noticeable change in the injectability. The mechanical properties of the hybrid hydrogels were enhanced by varying the dosage of graphene between 0.025 and 0.075 w/v%. In this range, the hybrid hydrogels preserve their integrity during mechanical test and recover the initial shape after removing the applied stress. Meanwhile, hybrid hydrogels with graphene content of up to 0.05 w/v% exhibit good biocompatibility for 3T3-L1 fibroblasts; the cells proliferate inside the gel structure and show higher spreading after 48 h. These injectable hybrid hydrogels with graphene have promising future as materials for tissue repair.

Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems, Part II: Long-Term Stability and Clinical Ocular Biopermanence.

BACKGROUND: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed. METHODS: Long-term stability at -20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters. RESULTS: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time. CONCLUSIONS: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at -20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.

Isosorbide plasticized corn starch filled with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microparticles: Properties and behavior under environmental factors.

In this work, new green and fully biodegradable composites, based on corn starch, plasticized with two different amounts of isosorbide and filled by poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microparticles, were obtained by melt processing. The analysis of their morphologies, crystallinity, structural interactions and dynamomechanical properties as well as the evaluation of their moisture resistance and biodegradability in soil, were performed in function of the plasticizer and/or microparticle amount. The analysis of morphology, crystallinity and structural interactions showed that the plasticization process was completed under the melting processing conditions used. The microparticles were homogeneously dispersed in the thermoplastic starch matrix without suffering any deformation or breaking during the processing. Biocomposites with adequate storage modulus values were obtained, especially the TPS plasticized with 35% of isosorbide and filled with 5 wt% of PHBV microparticles. The incorporation of PHBV microparticles leads to biocomposites with higher moisture resistance. All the biocomposites were completely biodegraded in soil in a short period of time. The performed study demonstrated that these biocomposites could be used for applications in the packaging industry.

Effect of Different Plasticizers on Thermal, Crystalline, and Permeability Properties of Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) Films.

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH) films were prepared using a cast film technique. Dioxane was chosen over other polymer solvents as it resulted in homogenous films with better morphology. Several plasticizers with different molecular weights and concentrations were added to the biopolymer solution prior to casting. Thermal, crystalline, and permeability properties were analyzed by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and both water vapor and oxygen transmission rate analysis. In general, the addition of plasticizers decreased the glass transition temperature (Tg), cold crystallization temperatures (Tcc), melting temperatures, as well as crystallinity degrees and increased the crystallite sizes and water vapor and oxygen transmission rates. The use of isosorbide and low-molecular-weight poly(ethylene glycol) (PEG) lowered the Tg around 30 °C at the highest used concentration, also being the most effective in increasing the crystallite size. When considering isosorbide and low-molecular-weight poly(ethylene glycol) (PEG) as very good plasticizers for PHBH, the question of which plasticizer to use strongly relies on the desired PHBH application.

Properties and behavior under environmental factors of isosorbide-plasticized starch reinforced with microcrystalline cellulose biocomposites.

Green biocomposites based on corn starch plasticized with isosorbide and glycerol and filled with microcrystalline cellulose (MCC) were processed. The structural interactions, dynamomechanical properties, water absorption, and soil biodegradability were investigated by different techniques considering the effect of the type and amount of plasticizer and the MCC addition. The changes along the time of the structural interactions and the dynamomechanical properties of these materials and the influence of the retrogradation phenomenon were also studied. The use of isosorbide as plasticizer instead of glycerol improved the stiffness, the water absorption and the biodegradation rate of thermoplastic starch (TPS). Moreover, no evidence of retrogradation for isosorbide was observed. An isosorbide content of 35% and the addition of MCC filler enhanced in a greater extent these properties with a complete biodegradability in 7 month. These green biocomposites can be an alternative for food packaging applications.

Corn starch plasticized with isosorbide and filled with microcrystalline cellulose: Processing and characterization.

Innovative, green and fully biodegradable biocomposites, based on plasticized corn starch, were prepared by melt processing and filled with microcrystalline cellulose (MCC). Isosorbide and glycerol were used as plasticizers. The effect of the type and content of the plasticizer and the filler addition on processing, surface morphologies, crystallinity and thermal stability were investigated. Aged materials were analyzed too to study the retrogradation phenomena along the time. The processing using isosorbide required lower temperatures but greater shear and processing times leading to more homogeneous biocomposites. With isosorbide, higher crystallinity and no retrogradation signals were observed as clearly occurred with glycerol. The thermal stability of biocomposites was high too. These properties enhanced in a greater extent when the isosorbide content was 35% and with the MCC incorporation, the last due to a good adhesion of MCC to the matrix. These biocomposites could be a good option for packaging applications.

Effects of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) microparticles on morphological, mechanical, thermal, and barrier properties in thermoplastic potato starch films.

Biocomposites of potato starch/poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microparticles were prepared through the solvent casting method. Glycerol was used as a plasticizer. The effects of concentrations of PHBV microparticles as filler and glycerol on crystallinity behavior, surface morphology, dynamic mechanical properties, and thermal stability were studied. Humidity absorption and the water vapor transmission rate (WVTR) were investigated as well. Wide angle X-ray scattering (WAXS) patterns revealed that the plasticizing process occurred successfully. Scanning electron microscopy (SEM) micrographs exhibited good homogeneity of the surfaces for the biocomposites with a lower glycerol concentration. Dynamic mechanical analysis (DMA) results confirmed the reinforcing effect of PHBV microparticles inside the matrix. Thermogravimetric analysis (TGA) indicated that the presence of PHBV microparticles increased the thermal stability of the starch. Results of humidity absorption tests showed that the high hydrophilicity of the starch was reduced once the PHBV microparticles had been incorporated. Also, increasing PHBV microparticles reduced the water vapor transmission rate. However, samples with reduced glycerol content absorbed less humidity and showed a lower water vapor transmission rate.

Preparation of starch nanoparticles loaded with quercetin using nanoprecipitation technique.

Nanoparticles of starches from different botanical origin were prepared by nanoprecipitation using 0.1M hydrochloric acid as non-solvent. The morphology and the particle size were analyzed using field emission scanning electron microscopy and dynamic light scattering. The nanoparticles were spherical and their sizes vary depending on the origin and the concentration of the starch solution. Starch nanoparticles loaded with quercetin were prepared. In-vitro release studies of the quercetin from the starch nanoparticles were performed in 35% ethanol as a release medium. The starch origin affects the quercetin loading percentage, the release kinetics and the antioxidant activity of the produced nanoparticles. The starch-quercetin nanoparticles from cereal origin showed the lowest loading percentage and the lowest fraction released of quercetin in comparison with nanoparticles from tuber and legume origin. The release kinetics seem to be controlled mainly by Fickian diffusion which have been revealed fitting the release data to the Peppas-Sahlin model.

Starch films loaded with donut-shaped starch-quercetin microparticles: Characterization and release kinetics.

Starch films loaded with donut-shaped starch-quercetin microparticles were prepared from two different botanical origins. The quercetin release kinetics through the films were studied. The donut-shaped starch-quercetin microparticles were prepared by thermal aqueous-alcoholic treatment. The quercetin loading percentage and therefore the antioxidant activity were higher for the microparticles from legume than those of cereal origins. The starch-quercetin microparticles also showed higher thermal stability than the starch granules. The starch films were produced using the solution casting method. The films with more microparticles content showed higher thermal stability. In-vitro release studies of the quercetin through the films were performed in aqueous-ethanolic medium. The quercetin released reached the equilibrium in 1 to 4 days for the films of cereal starch and in more than a week for the films of legume origin. The release data were fitted to Peppas-Sahlin model that suggests the release kinetics were controlled mainly by fickian diffusion. The produced biofilms can be utilized mainly for active food packaging applications.

Effect of nanocellulose as a filler on biodegradable thermoplastic starch films from tuber, cereal and legume.

Starches from different vegetal sources (tuber, cereal and legume) were plasticized with an invariant glycerol content and reinforced with cellulose nanocrystals by solution casting method. The influence of both, starch nature and filler amount, in the crystallinity and the extension of plasticization have been analyzed by X-ray diffraction. Thermoplastic starches (TPS) morphologies were obtained by scanning electron microscopy. Mechanical properties and thermal stability were analyzed by dynamomechanical and thermogravimetric analysis. Water absorption evolution was studied as well. A major extension in plasticization (high amylopectin starches) led to matrices with large starch-rich domains, a good thermal stability and resistance to water absorption but low stiffness. The incorporation of cellulose nanoparticles favoured plasticization and increased the rigidity in TPS films, as well as the thermal stability and moisture resistance. The aim of this work was to obtain bio-based thermoplastic starch films for replacing petroleum-derived ones in packaging industry, especially for short-life applications.