Antiepileptic drug-loaded and multifunctional iron oxide@silica@gelatin nanoparticles for acid-triggered drug delivery.

The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g-1. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04 nm, which is in the desired size range facilitating entry through the blood-brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks.

Facile encapsulation of cyanoacrylate-based bioadhesive by electrospray method and investigation of the process parameters.

Polymer microcapsules containing cyanoacrylates have represented a promising option to develop self-healing biomaterials. This study aims to develop an electrospray method for the preparation of capsules using poly(methyl methacrylate) (PMMA) as the encapsulant and ethyl 2-cyanoacrylate (EC) as the encapsulate. It also aims to study the effect of the electrospray process parameters on the size and morphology of the capsules. The capsules were characterized using Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and field-emission scanning electron microscopy (FE-SEM). Moreover, the effects of electrospray process parameters on the size were investigated by Taguchi experimental design. FTIR and TGA approved the presence of both PMMA and EC without further reaction. FE-SEM micrograph demonstrated that an appropriate choice of solvents, utilizing an appropriate PMMA:EC ratio and sufficient PMMA concentration are critical factors to produce capsules dominantly with an intact and spherical morphology. Utilizing various flow rates (0.3-0.5 ml/h) and applied voltage (18-26 kV), capsules were obtained with a 600-1000 nm size range. At constantly applied voltages, the increase in flow rate increased the capsule size up to 40% (ANOVA, p ≤ 0.05), while at constant flow rates, the increase in applied voltage reduced the average capsule size by 3.4-26% (ANOVA, p ≤ 0.05). The results from the Taguchi design represented the significance of solution flow rate, applied voltage, and solution concentration. It was shown that the most effective parameter on the size of capsules is flow rate. This research demonstrated that electrospray can be utilized as a convenient method for the preparation of sub-micron PMMA capsules containing EC. Furthermore, the morphology of the capsules is dominated by solvents, PMMA concentration, and PMMA:EC ratio, while the average size of the capsules can be altered by adjusting the flow rate and applied voltage of the electrospray process.

Self-healing interpenetrating network hydrogel based on GelMA/alginate/nano-clay.

Today, tissue engineering strategies need the improvement of advanced hydrogels with biological and mechanical properties similar to natural cartilage for joint regeneration. In this study, an interpenetrating network (IPN) hydrogel composed of gelatin methacrylate (GelMA)/alginate (Algin)/nano-clay (NC) with self-healing ability was developed with particular consideration to balancing of the mechanical properties and biocompatibility of bioink material. Subsequently, the properties of the synthesized nanocomposite IPN, including the chemical structure, rheological behavior, physical properties (i.e. porosity and swelling), mechanical properties, biocompatibility, and self-healing performance were evaluated to investigate the potential application of the developed hydrogel for cartilage tissue engineering (CTE). The synthesized hydrogels showed highly porous structures with dissimilar pore sizes. The results revealed that the NC incorporation improved the properties of GelMA/Algin IPN, such as porosity, and mechanical strength (reached 170 ± 3.5 kPa), while the NC incorporation decreased the degradation (63.8 %) along with retaining biocompatibility. Therefore, the developed hydrogel showed a promising potential for the treatment of tissue defects in cartilage.

Nanofibrous Scaffolds with Biomimetic Composition for Skin Regeneration.

Treatments of skin injuries caused by trauma and diseases are among the most considerable medical problems. The use of scaffolds that can cover the wound area and support cellular ingrowth has shown great promise. However, mimicking the physicochemical properties of the native skin extracellular matrix (ECM) is essential for the successful integration of these scaffolds. Elastin has been known as the second main protein-based component of the native skin ECM. In this research, scaffolds containing gelatin, cellulose acetate, and elastin were fabricated using electrospinning. Subsequently, the effects of soluble elastin on the physical, mechanical, and biological properties of the prepared scaffolds were studied. The results confirmed that the presence of elastin in the composition changed the fiber morphology from straight to ribbon-like structure and decreased the swelling ratio and degradation rate of the scaffold. In vitro experiments showed that elastin-containing scaffolds supported the attachment and proliferation of fibroblast cells. Overall, the obtained results suggest the ternary blend of gelatin, cellulose acetate, and elastin as a good candidate for skin tissue engineering.

Adsorption of tetracycline from water using glutaraldehyde-crosslinked electrospun nanofibers of chitosan/poly(vinyl alcohol).

In this work, the preparation and characterization of glutaraldehyde-crosslinked electrospun nanofibers of chitosan/poly(vinyl alcohol) (GCCPN) as a new adsorbent for tetracycline (TC) is reported. Electrospun nanofibers of chitosan/poly(vinyl alcohol) (PVA) were prepared by employing a 75:25 volumetric ratio of chitosan:PVA, voltage of 30 kV, collection distance of 10 cm, and injection flow rate of 2 mL/h. Then, the nanofibers were crosslinked via applying the glutaraldehyde on them for 3 h at 40 °C. The nanofibers were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction. Uniform beadless nanofibers with minimum diameters of 3-11 and 6-18 nm were obtained before and after crosslinking, respectively. Then the applicability of the synthesized GCCPN for removal of TC from aqueous solutions was investigated. The response surface method was applied to evaluate the influence of pH (6-12), TC concentration (50-250 mg/L) and the adsorbent dose (0.05-0.25 g in 20 mL solution) on the adsorption characteristics of GCCPN. The maximum adsorption capacity was 102 mg/g. The adsorption kinetics was explained most effectively by the pseudo-second-order model. The adsorption data of TC on the GCCPN surface was explained well by the Langmuir isotherm model.

Design and characterization of dexamethasone-loaded poly (glycerol sebacate)-poly caprolactone/gelatin scaffold by coaxial electro spinning for soft tissue engineering.

The aim of this research was to fabricate dexamethasone (Dex)-loaded poly (glycerol sebacate) (PGS)-poly (caprolactone) (PCL)/gelatin (Gt) (PGS-PCL/Gt-Dex) fibrous scaffolds in the form of core/shell structure which have potential application in soft tissues. In this regard, after synthesize and characterizations of PGS, PGS-PCL and gelatin fibrous scaffolds were separately developed in order to optimize the electrospinning parameters. In the next step, coaxial electrospun fibrous scaffold of PGS-PCL/Gt fibrous scaffold with PGS-PCL as core and Gt as shell was developed and its mechanical, physical and chemical properties were characterized. Moreover, degradability, hydrophilicity and biocompatibility of PGS-PCL/Gt fibrous scaffold were evaluated. In addition, Dex was encapsulated in PGS-PCL/Gt fibrous scaffold and drug release was assessed for tissue engineering application. Results demonstrated the formation of coaxial fibrous scaffold with average porosity of 79% and average fiber size of 294nm. Moreover, PGS-PCL/Gt fibrous scaffold revealed lower elastic modulus, ultimate tensile and ultimate elongation than those of PGS-PCL scaffold and more close to mechanical properties of natural tissue. Furthermore, lower contact angle of PGS-PCL/Gt than that of PGS-PCL demonstrated improved surface hydrophilicity of scaffold. DEX release was sustained over a period time of 30days from the scaffolds via three steps consisting of an initial burst release, secondary linear phase release pattern with slower rate over 20days followed by an apparent zero-order release phase. MTT observations demonstrated that there was no evidence of toxicity in the samples with and without Dex. Our findings indicated that core/shell PGS-PCL/Gt-Dex fibrous could be used as a carrier for the sustained release of drugs relevant for tissue engineering which makes it appropriate for soft tissue engineering.

Preparation and characterization of poly (hydroxy butyrate)/chitosan blend scaffolds for tissue engineering applications.

BACKGROUND: Poly (hydroxy butyrate) (PHB) is a biodegradable and biocompatible polymer with good mechanical properties. This polymer could be a promising material for scaffolds if some features improve. MATERIALS AND METHODS: In the present work, new PHB/chitosan blend scaffolds were prepared as a three-dimensional substrate in cartilage tissue engineering. Chitosan in different weight percent was added to PHB and solved in trifluoroacetic acid. Statistical Taguchi method was employed in the design of experiments. RESULTS: The Fourier-transform infrared spectroscopy test revealed that the crystallization of PHB in these blends is suppressed with increasing the amount of chitosan. Scanning electron microscopy images showed a thin and rough top layer with a nodular structure, supported with a porous sub-layer in the surface of the scaffolds. In vitro degradation rate of the scaffolds was higher than pure PHB scaffolds. Maximum degradation rate has been seen for the scaffold with 90% wt. NaCl and 40% wt. chitosan. CONCLUSIONS: The obtained results suggest that these newly developed PHB/chitosan blend scaffolds may serve as a three-dimensional substrate in cartilage tissue engineering.

Synthesis and Gelation Characteristics of Photo-Crosslinkable Star Poly(ethylene oxide-co-lactide-glycolide acrylate) Macromonomers.

Viability of encapsulated cells in situ crosslinkable macromonomers depends strongly on the minimum concentration of polymerization initiators and monomers required for gelation. Novel 4-arm poly(ethylene oxide-co-lactide-glycolide acrylate) (SPELGA) macromonomers were synthesized and characterized with respect to gelation, sol fraction, degradation, and swelling in aqueous solution. SPELGA macromonomers were crosslinked in the absence of N-vinyl-2-pyrrolidone (NVP) monomer to produce a hydrogel network with a shear modulus of 27±4 kPa. The shear modulus of the gels increased by 170-fold as the macromonomer concentration was increased from 10 to 25 wt%. Sol fraction ranged between 8-18%. Addition of only 0.4 mol% NVP to the polymerization mixture increased modulus by 2.2-fold from 27±4 (no NVP) to 60±10 kPa. The higher modulus was attributed to the dilution effect of polymer chains in the sol, by delaying the onset of diffusion-controlled reaction, and cross-propagation of the growing chains with network-bound SPELGA acrylates. Degradation of SPELGA gels depended on water content and density of hydrolytically degradable ester groups.