Synthesis of resilient hybrid hydrogels using UiO-66 MOFs and alginate (hydroMOFs) and their effect on mechanical and matter transport properties.

Herein, we report the preparation of an organic-inorganic hybrid hydrogel architecture using vinyl alginate and UiO-66 MOFs (metal-organic frameworks) modified with acrylic acid (AA) UiO-66AA. UiO-66 MOFs with different crystal sizes (600, 1500, and 2500 nm) were synthesized and the effect on the mechanical and transport properties of the resulting materials, such as water absorption capacity and drug release, were evaluated. HydroMOF showed higher water absorption capacity than the pure hydrogel and enhanced mechanical properties, which depend on crystal size and the amount of UiO-66AA MOF used. The initial release rate of drug (burst release) from hydroMOFs was lower when small-sized crystals or a small amount of large-sized crystals were used; thus these are essential in changing half-life values of release rates. Finally, the cytotoxicity screening successfully showed that hydroMOFs are promising biocompatible compounds proven to have the advantages of minimized burst release and mechanical robustness.

MCM-41/chondroitin sulfate hybrid hydrogels with remarkable mechanical properties and superabsorption of methylene blue.

This paper describes the synthesis of hybrid hydrogels based on chondroitin sulfate (CS) and mesoporous silica (MCM-41). The combination of the CS network and surface-modified MCM-41 yields resilient hybrids with a high water absorption power and excellent capacity for the removal of methylene blue (MB). In this system, two types of solute transport mechanisms exist: absorption and adsorption. The effect of MCM-41 on the physical-chemical properties of the hydrogels was assessed over a wide pH scale, and the absorption kinetics and isotherms of MB were studied by theoretical models. The mechanical properties of the hydrogels, such as the modulus of elasticity, yield strength, modulus of resilience, and fracture toughness, were significantly improved. This hydrogel exhibited high performance for water absorption (4000 % beyond its initial weight) and removal of MB (3982 ± 123.6 mg g-1), while the pure hydrogel removed 2912 ± 163.8 mg g-1.

Bionanocomposites based on mesoporous silica and alginate for enhanced drug delivery.

This work reports the preparation, the characterization and the prednisolone release profile of biocompatible hydrogel nanocomposites containing mesoporous silica (SBA) and alginate as a biomaterial for enhanced drug delivery with reduced burst effect and improved mechanical properties. Such systems, which were prepared using specific SBA/alginate-crosslinking chemistry, exhibited interconnecting pore hybrid network owing to both mesoporous silica and hydrogel characteristics. Activated SBA was shown to be a determinant factor in inhibiting initial burst by nearly 90% and the drug was released with minimal burst kinetics. The nanoparticles reduced the movements of polymer chains, affecting macromolecular relaxation, and the distribution of mesoporous silica within the hydrogel made drug release into surrounding liquid less favorable. The proposed systems are biocompatible with human immortalized RWPE-1 prostatic epithelial cells. This report offers an approach of up-to-date interest for the development of advanced biomaterials for further physiological and pathological applications.

Chitosan-based hydrogels: From preparation to biomedical applications.

The advances in the field of biomaterials have led to several studies on alternative biocompatible devices and to their development focusing on their properties, benefits, limitations, and utilization of alternative resources. Due to their advantages like biocompatibility, biodegradability, and low cost, polysaccharides have been widely used in the development of hydrogels. Among the polysaccharides studied on hydrogels preparation, chitosan (pure or combined with natural/synthetic polymers) have been widely investigated for use in biomedical field. In view of potential applications of chitosan-based hydrogels, this review focuses on the most recent progress made with respect to preparation, properties, and their salient accomplishments for drug delivery and tissue engineering.

Synthesis of a microhydrogel composite from cellulose nanowhiskers and starch for drug delivery.

This work describes the preparation of a microhydrogel composite from cellulose nanowhiskers (CNW) and starch in an ultrasound assisted-emulsion. CNW, which showed rod-like morphology, was obtained by acid hydrolysis of cane-based cellulose. The introduction of vinyl bonds to both CNW and starch enabled us to create the microhydrogel composite in which CNW played a role as a covalent cross-linker. Furthermore, CNW may act as an emulsifying agent for emulsion, improving both sphericity and homogeneity of the microparticles. The drug release was regulated in response to changes in the CNW amounts. The modeling of the release kinetics indicated that the drug release is driven by an anomalous mechanism and that the addition of CNW to starch microparticles led to differences in that mechanism. The release rate became ca. 2.9 times slower when CNW is added. When combined with starch, CNW played a role as a retardant factor for drug release.

Drug release mechanisms of chemically cross-linked albumin microparticles: effect of the matrix erosion.

Albumin (BSA) microparticles were developed as a biotechnological alternative for drug delivery. Vitamin B12 (Vit-B12) was used as a model drug. The microparticles were obtained from maleic anhydride-functionalized BSA and N',N'-dimethylacrylamide (DMAAm) in a W/O emulsion without and with PVA. The microparticles produced at 15min of stirring without PVA showed the best results in terms of size, homogeneity, and sphericity. In such a case, BSA played a role as a surface active agent, replacing PVA. For longer stirring times, BSA was unable to act as an emulsifier. These microparticles showed an uncommon release profile, consisting of a two-step release mechanism, at the pH range studied. Considering that a two-step release mechanism is occurring, the experimental data were adjusted by applying modified power law and Weibull equations in order to describe release mechanism n and release rate constant k, respectively. Each one of the release stages was related to a specific value of n and k. The second stage was driven by a super case II transport mechanism, as a result of diffusion, macromolecular relaxation, and erosion. A third model, described by Hixson-Crowell, confirmed the erosion mechanism. Vit-B12 diffusion kinetics in aqueous solutions (i.e., without the microparticles) follows a one-step process, being k dependent on the pH, confirming that the two-step release mechanism is a characteristic profile of the developed microparticles. The microparticles released only 2.70% of their initial drug load at pH 2, and 58.53% at pH 10.

Covalent TiO(2)/pectin microspheres with Fe(3)O(4) nanoparticles for magnetic field-modulated drug delivery.

Covalent TiO(2)-co-pectin microspheres containing Fe(3)O(4) nanoparticles were developed through an ultrasound-induced crosslinking/polymerization reaction between the glycidyl methacrylate from vinyl groups in TiO(2) and in pectin. ζ-potentials became less negative in the nanostructured microspheres, caused by the presence of both inorganic particles in the negatively charged pectin. The nanostructured pectin microspheres showed an amoxicillin release rate slower than that of pure pectin microspheres. The proposed microspheres were found to be a sustained release system of amoxicillin in the acid medium. Furthermore, the antibiotic release may be modulated by exposition of the microspheres to a remote magnetic field. In practical terms, the nanostructured microspheres could deliver a larger proportion of their initial load to specific site of action. The cytotoxic concentrations for 50% of VERO cells (CC(50)), calculated as the concentration required to reduce cell viability by 50% after 72h of incubation, for pectin-only microspheres and nanostructured pectin microspheres were 217.7±6.5 and 121.5±4.9µgmL(-1), respectively. The obtained CC(50) values indicated acceptable cytotoxic levels for an incubation period of 72h, showing that the pectin microspheres have a great pharmacological potential for uses in biological environments, even after the introduction of both Fe(3)O(4) and TiO(2).

Covalent albumin microparticles as an adjuvant for production of mucosal vaccines against hepatitis B.

Covalently modified albumin (BSA) microparticles were developed for potential use as an adjuvant in mucosal vaccines against hepatitis B. To synthesize consistent protein particles, a covalent approach was proposed to modify BSA. Our strategy was to bond maleic anhydride (MA) molecules to BSA structure by nucleophilic reaction for further radical cross-linking/polymerization reaction with N',N'-dimethylacrylamide (DMAAm). The presence of poly(N',N'-dimethylacrylamide) in the protein network enables the microparticles to show well-defined, homogeneous forms. Cytotoxicity tests showed that the cytotoxic concentration for 50% of VERO cells (CC50) was 216.25 ± 5.30 µg mL(-1) in 72 h of incubation. The obtained CC50 value is relatively low for an incubation time of 72 h, suggesting an acceptable biocompatibility. Assay of total protein showed that the encapsulation efficiency of the microparticles with hepatitis B surface antigen (HBsAg) was 77.7 ± 0.2%. For the reference sample, which was incubated without HBsAg, the quantity of protein was below the limit of detection.

Synthesis of a thermosensitive surface by construction of a thin layer of poly (N-isopropylacrylamide) on maleimide-immobilized polypropylene.

Thermosensitive surfaces were developed by the grafting of a thin layer of PNIPAAm through an UV-induced photopolymerization reaction of vinyl monomers with a free radical-activated polypropylene (PP) surface. PNIPAAm layer covering the PP surface corrected, to some extension, both depressions and fissures of the previously modified PP surfaces. The layered surfaces have morphological characteristic different from those of the non-layered surfaces, and their thickness was dependent on irradiation time. Water contact angles of the layered surfaces revealed a transition at approximately 33.5-36.5 °C as a result of a response to the variation of temperature. There was an increase in the values of the contact angles with an increase in temperature from 26 °C to 44 °C, revealing the nature both hydrophilic and hydrophobic of the surfaces due to a conformational rearrangement of PNIPAAm exposing its isopropyl groups to the liquid drop. This work offers a chemically stable thermosensitive surface (because it is covalently structured) with great potential for use as sensors and actuators.

Solid-state radical grafting reaction of glycidyl methacrylate and poly(4-methyl-1-pentene) in supercritical carbon dioxide: surface morphology and adhesion.

Solid-state radical grafting of glycidyl methacrylate (GMA) onto poly(4-methyl-1-pentene) (PMP) was performed using supercritical carbon dioxide (scCO(2)) impregnation technology. The polymer films were firstly impregnated in the scCO(2) phase with the GMA using benzoyl peroxide as thermal initiator. The grafting degree and surface morphology of the samples may be controlled by the following factors: time, temperature, and pressure of impregnation. A 2(3) factorial design to evaluate the main and interaction effects of such factors on the grafting of the PMP by GMA (grafting response) was elaborated from FTIR data. The superior and inferior limits of the levels were defined on basis of a P-x-y diagram for binary system CO(2)+GMA that provided the location of the transition curves of such a system. Better grafting response was obtained for pressure of 130 bar, temperature of 70°C and time of 7h. The PMP-g-GMA films exhibited a thermal profile similar to that of the unmodified polymer. Adhesion characteristics of polymer films are dependent on grafting degree of GMA.

Smart hollow microspheres of chondroitin sulfate conjugates and magnetite nanoparticles for magnetic vector.

Smart hollow microspheres composed of vinyled-chondroitin sulfate conjugates (CSπ) and magnetite nanoparticles were obtained by the intermediate of a multiple emulsion in absence of a surfactant, attributable to stabilizing properties of the CS. It was formed an oil-water multiple emulsion in which the CS played a role as an anionic stabilizer for magnetite nanoparticles via complexation. Iron oxides were bonded to the microspheres by the formation of a complex of Fe(3+) ions on the crystalline phase with oxygen atoms at the carboxyl groups without their magnetic properties being affected. The average crystal size of embedded magnetite nanoparticles was approximately 16.5nm, indicative of a good dispersion in microspheres. Furthermore, the introduction of iron oxides resulted in microspheres with a higher diameter and a narrower particle size distribution.

Reaction of glycidyl methacrylate at the hydroxyl and carboxylic groups of poly(vinyl alcohol) and poly(acrylic acid): is this reaction mechanism still unclear?

Transesterification and epoxide ring-opening reactions are two mechanism routes that explain chemical modifications of macromolecules by glycidyl methacrylate (GMA). Although the coupling reaction of the GMA with macromolecules has widely been investigated, there are still mechanisms that remain to be explained when GMA is processed in an aqueous solution at different pH conditions. To this end, reaction mechanisms of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAAc) by GMA in water in acidic and basic conditions were investigated thoroughly. The presence of hydroxyl groups in PVA and carboxyl groups in PAAc allowed for a better evaluation of the reaction mechanisms. The analysis of the (1)H and (13)C NMR spectra clearly demonstrated that the chemical reactions of GMA with carboxyl groups and alcohols of the macromolecules in an aqueous solution are dependent on pH conditions. At pH 3.5, the GMA reacts with both the carboxylic and the hydroxyl groups through an epoxide ring-opening mechanism. At pH 10.5, the GMA undergoes a hydrolysis process and reacts with hydroxyl groups by way of both the transesterification and the epoxide ring-opening mechanisms, whereas the ring-opening reaction is the preferential pathway.

Synthesis and water absorption transport mechanism of a pH-sensitive polymer network structured on vinyl-functionalized pectin.

Polysaccharide-structured copolymer hydrogel having excellent pH-sensitivity was developed from N,N-dimethylacrylamide (DMAc) and vinyl-functionalized Pectin (Pec). The Pec was vinyl-functionalized by way of chemical reaction with glycidyl metacrylate (GMA) in water under acidic and thermal stimuli. 13C NMR, 1H NMR, and FT-IR spectra revealed that the vinyl groups coming from the GMA were attached onto backbone of the polysaccharide. The hydrogels were obtained by polymerization of the Pec-vinyl with the DMAc. 13C-CP/MAS NMR and FTIR spectra confirmed that the gelling process occurred by way of the vinyl groups attached on Pec-vinyl backbone. The values of apparent swelling rate constant (k) decreased appreciably for pH greater than 6, demonstrating the swelling process of the hydrogel becomes slower at more alkaline conditions. There was an increase of diffusional exponent (n) with increasing pH of the surrounding liquid. This means the water absorption profile becomes more dependent on the polymer relaxation in basified swelling media. In this condition, a longer water absorption half-time (t1/2) was verified, suggesting the polymer relaxation mechanism of the hydrogel would have a considerable effect on the t1/2.

Synthesis of hollow-structured nano- and microspheres from pectin in a nanodroplet emulsion.

Hollow-structured nano- and microspheres with diameters ranging from 24 microm to 160 nm were successfully produced from chemically modified pectin (Ma-Pec) through a two-step synthesis. In a first step, the Pec was modified with glycidyl methacrylate (GMA) in a heterogeneous phase system, indeed consisting of water-soluble Pec and water-insoluble GMA, via an interfacial reaction at the interface of the GMA-water phase system after 12 h under continuous stirring of 1000 rpm at 60 degrees C. In a second step, the spheres were prepared in a water-in-benzyl alcohol nanodroplet emulsion at 12000 rpm under a bubbling stream of nitrogen in the presence of sodium persulfate, as initiator, and TEMED, as catalytic agent. FT-IR spectra revealed that the vinyl groups (CC) coming from the GMA were attached onto backbone of the polysaccharide. 13C-CP/MAS NMR spectra demonstrated that the spheres were formed via carbon-carbon pi-bonds on Ma-Pec in the water phase, for the duration of the dispersion stage. The dark center (an empty core) and edge of the hollow spheres could be easily identified by SEM micrographs. This type of polymer structure represents a class of unique material with particular importance in terms of state-of the-art applications in both nano- and microencapsulation of drugs, for example, protection shields of biologically active agents.

Nanometer- and submicrometer-sized hollow spheres of chondroitin sulfate as a potential formulation strategy for anti-inflammatory encapsulation.

PURPOSE: The synthesis of nanometer and submicrometer hollow particles could be a motivating way to imprint new therapeutic properties into a chondroitin sulfate-based hydrogel formulation. The use of hollowed polymer structures as a formulation strategy is expected to have an impact in the effective therapy in the treatment of rheumatoid arthritis. METHODS: Chemical modification of the chondroitin sulfate with glycidyl methacrylate (GMA) was performed in water under thermal and acid stimuli. The hydrogel spheres were formed upon cross-linking reaction of modified chondroitin sulfate (CSM) in a water-in-benzyl alcohol nano-droplet emulsion. RESULTS: 1H NMR and 13C NMR spectra showed that the carbon-carbon pi-bonds coming from the GMA were incorporated onto backbones of CS. 13C-CP/MAS NMR spectra revealed that the formation of the CSM hydrogel spheres during the dispersion stage occurred by way of carbon-carbon pi-bonds on the CSM structure. The spherical shapes of the particles with diameters in the range of 20 microm to 500 nm were very clearly verified by SEM images where the dark center and edge of the hollow spheres could be identified easily. CONCLUSIONS: Nanometer- and submicrometer-sized hydrogel spheres with hollow interior were produced from chondroitin sulfate by using a new strategy of hydrogel synthesis.

Mathematical model for the prediction of the overall profile of in vitro solute release from polymer networks.

The loading of solutes onto and their release from hydrogel-based devices can be better understood when they are treated as a partition phenomenon. Partition activity (alpha) is a parameter that determines the existence of partition phenomena. It expresses the physical chemical affinities of the solute between the solvent and hydrogel phases. When alpha=0, there is no release of the solute from the hydrogel; however, if alpha>0, there is partitioning of the solute between the solvent and the hydrogel phases, and release of the solute from the hydrogel can be observed. The mathematic model proposed here predicts the overall release profile of vitamin B(12), methylene blue (MB), and acid orange 7 (AO) from semi-interpenetrating network (semi-IPN) hydrogels composed of PNIPAAm and PAAm. Experimental release tests demonstrated that alterations on variables of the system change both the released fraction and the release rate of such solutes, confirmed by the changes on values of alpha (an equilibrium parameter) and k(R) (an kinetic parameter). The modeling of solute release describes the alpha effects on release of the solute from polymer networks. The solute release mechanism is viewed here as a diffusional transport process and as a partition phenomenon. The partitioning of the solutes occurs between the solvent phase and the hydrogel phase, and the possible physical chemical affinities of the solute between hydrogel and solvent are considered.

Capacity of adsorption of Pb2+ and Ni2+ from aqueous solutions by chitosan produced from silkworm chrysalides in different degrees of deacetylation.

The binding capacities of chitin (CT) and chitosan (CS) produced from silkworm chrysalides were investigated aiming at their future application in the removal of Pb2+ and Ni2+ from wastewaters. CS with 75% deacetylation degree (DD) exhibited good binding performance for Pb(2+), but bad efficiency for Ni2+. The maximum binding capacity obtained from isotherms for CS-Pb was 141.10 mg g(-1) and 52.81 mg g(-1) for CS-Ni. The binding capacities for CT were 32.01 mg g(-1) for Pb2+ and 61.24 mg g(-1) for Ni2+. The authors attribute these behaviors to two main factors: (i) the large ionic size of Pb2+ and (ii) the steric hindrance due to CT acetyl groups. Metal binding onto CS was evaluated by the Freundlich and Langmuir isotherm models. The parameter values obtained from the isotherm analysis confirmed that Pb2+ and Ni2+ interact differently with CS and that various factors influence their adsorption. Thermogravimetric analysis (TGA) showed that the thermal behavior of CS with 75% deacetylation degree was in the same profile of standard CS; however, the binding of the metals onto its structure affects the curve profile.

Removal of methylene blue dye from an aqueous media using superabsorbent hydrogel supported on modified polysaccharide.

The removal of methylene blue (MB) in water with the superabsorbent hydrogel (SH) formed by modified gum arabic, polyacrylate, and polyacrylamide was investigated. The SH exhibited excellent performance in MB absorption. The maximum absorption capacity was 48 mg of the dye per g of SH, representing 98% of the MB removed. Experimental parameters were used as follows: pH 8, hydrogel mass 50 mg, and initial concentration of MB 50 mg L(-1). In a procedure with an individual solution of orange II, an opposite effect related to the MB was observed: the hydrogel only absorbed water, resulting in an orange II-richer solution. The orange II concentration in solution increased about 50 times (relative to the initial concentration). In another experiment using an aqueous mixture of orange II and MB, the SH absorbed the MB exclusively. Compared to the MB, the orange II is separated from water by SH selectivity-absorption through an inverse process. This effect was attributed to the formation of a ionic complex between the imine groups of MB and the ionized carboxylic groups of SH.

Novel adsorbent based on silkworm chrysalides for removal of heavy metals from wastewaters.

In this contribution, maximum capacity for adsorption of Pb(2+), Ni(2+), and Cu(2+) by silkworm chrysalides (SC) was determined. The raw silkworm chrysalides (SC(r)) and chrysalides after acidic washing (SC(w)) were used. Chitin (CT), extracted from SC, and chitosan (CS), with 85% deacetylation, were employed as reference samples. Adsorption tests showed that all the studied adsorbents exhibited excellent performance in removal of metals. The choice of a more appropriate adsorbent is related to its efficiency for removal of a specific metal. The studied materials presented different intensities for metal adsorption as follows: (i) Ni(2+)>Cu(2+)>Pb(2+) for SC(r); (ii) Pb(2+)>Cu(2+)>Ni(2+) for SC(w); (iii) Ni(2+)>Cu(2+)>Pb(2+) for CT; and (iv) Cu(2+)>Pb(2+)>Ni(2+) for CS. Metal adsorption onto SC(r) and CS was analyzed by Freundlich and Langmuir isotherm equations. Adsorption values for CS-Pb and SC(r)-Ni were provided by the Freundlich model, while the adsorption values for CS-Cu, CS-Ni, SC(r)-Pb, and SC(r)-Cu were provided by the Langmuir model. The studied adsorbents are suitable for use in treatment of wastewater. From the economic point of view, the use of SC(r) as an adsorbent of heavy metals (mainly Ni(2+)) on the large industrial scale would be more appropriate.