Design and preparation of a novel pullulan hard capsule formulation: A promising green candidate and study of crucial capsule features.

Plant-based hard capsules have gained considerable attention because of their great properties. Accordingly, designing and developing of these kinds of capsules will be a difficult task. Herein, an innovative pullulan-based hard capsule formulation was prepared for the first time. A series of characterization approaches, including Fourier transform infrared, field emission scanning electron microscope, and rheology analysis, were utilized to figure out the straightforward preparation of a designed hard capsule. Many tests and experiments were performed to achieve the optimum capsule formulation. Based on the obtained results, specifications such as uniform downfall and non-desirable adhesion, and other ideal characteristics of the capsule display the critical function. The gelling promoter of divalent cationic salts is more beneficial than its single-valent counterparts. With respect to the key role of gelling promoter, the presence of chosen MgSO4.7H2O salt and the source of selected carrageenan are important parameters to achieve optimal formulation. Moreover, field emission scanning electron microscope images illustrate that the weight ratio of 3.5 (gelling agent to salt) displays uniform surface morphology without any impurities or other foreign materials. Likewise, the outcomes of the rheology test also illustrated that the weight ratio of 3.5 is preferable. Considering the different weight ratios, the benefits of a weight ratio of 3.5 outweigh the other investigated ratios. Overall, the current research addresses substantial information about developing pullulan-based hard capsules for target usage.

Industrial Manufacture of Enteric Hard Capsules Using Novel Formulations Based on Hypromellose Phthalate/Gelatin and Investigation of Pantoprazole Release.

Capsules are popular oral dosage forms because of their ease of production. They are widespread pharmaceutical products. Hard capsules are preferred dosage forms for new medicines undergoing clinical tests because they do not require expansive formulation development. Functional capsules with built-in gastroresistance, aside from the traditional hard-gelatin or cellulose-based vegetarian capsules, would be beneficial. In this research, the effect of polyethylene glycol-4000 (PEG-4000) was investigated on the formulation of uncoated enteric hard capsules based on hypromellose phthalate (HPMCPh) and gelatin. Three different formulations based on HPMCPh, gelatin, and PEG-4000 were tested to achieve the optimal formulation for the industrial production of hard enteric capsules with desired physicochemical and enteric properties. The results reveal that the capsules containing HPMCPh, gelatin, and PEG-4000 (F1) are stable in the stomach environment (pH = 1.2) for 120 min, and during this time, no release happens. The outcomes also demonstrate that PEG-4000 blocks the pores and improves enteric hard capsule formulation. In this research, we present a specific procedure for manufacturing uncoated enteric hard capsules on an industrial scale that does not require an extra coating step for the first time. The industrial-scale validated process can considerably reduce the cost of manufacturing standard enteric-coated dosage forms.

Boosting bone cell growth using nanofibrous carboxymethylated cellulose and chitosan on titanium dioxide nanotube array with dual surface charges as a novel multifunctional bioimplant surface.

One of the most vital aspects of the orthopedic implant field has been the development of multifunctional coatings that improve bone-implant contact while simultaneously preventing bacterial infection. The present study investigates the fabrication and characterization of multifunctional polysaccharides, including carboxymethyl cellulose (CMCn) and carboxymethyl chitosan nanofibers (CMCHn), as a novel implant coating on titania nanotube arrays (T). Field emission scanning electron microscopy (FESEM) images revealed a nanofibrous morphology with a narrow diameter for CMCn and CMCHn, similar to extracellular matrix nanostructures. Compared to the T surface, the roughness of CMCn and CMCHn samples increased by over 250 %. An improved cell proliferation rate was observed on CMCHn nanofibers with a positively charged surface caused by the amino groups. Furthermore, in an antibacterial experiment, CMCn and CMCHn inhibited bacterial colony formation by 80 % and 73 %, respectively. According to the results, constructed modified CMCn and CMCHn increased osteoblast cell survival while inhibiting bacterial biofilm formation owing to their surface charge and bioinspired physicochemical properties.

Microfluidic assisted low-temperature and speedy synthesis of TiO2/ZnO/GOx with bio/photo active cites for amoxicillin degradation.

For the first time, a bio-photo-catalyst is synthesized in a microfluidic platform. The microchannel, which is wall-coated by in situ synthesized bio-photo-catalyst is used as an opto-fluidic reactor for amoxicillin degradation. Analyses including SEM, XRD, FTIR, Raman, UV-Vis spectra, and DLS have been used to characterize samples. The structure and morphology of TiO2 in microfluidic assisted synthesis are studied at 70-120 °C. The results show that both single-crystalline anatase sample and two-phase samples of anatase and rutile can be attained. According to SEM images, the smallest size and the narrowest particle size distribution (0.86 nm [Formula: see text]) is achieved by synthesis at 70 °C. Elemental mapping of Ti shows a uniform coating layer on inner walls. Raman signals besides the primary amines in FTIR results show the biological activity of the cross-linked Glucose oxidase (GOx), which is aimed for situ generation of H2O2. FTIR comparison of bulk and spiral microfluidic synthesized ZnO indicates identical bonds. SEM-coupled with performance experimentation reveal that by regulating the flowrate of spiral micromixer for ZnCl2 at 25 µl/min and NaOH at 50 µl/min, the narrowest size distribution and best the bio-photo-catalytic performance of ZnO nanoparticles is observed.

In-situ forming hydrogel based on thiolated chitosan/carboxymethyl cellulose (CMC) containing borate bioactive glass for wound healing.

Suitable wound dressings for accelerating wound healing are actively being designed and synthesised. In this study, thiolated chitosan (tCh)/oxidized carboxymethyl cellulose (OCMC) hydrogel containing Cu-doped borate bioglass (BG) was developed as a wound dressing to improve wound healing in a full-thickness skin defect of mouse animal model. Thiolation was used to incorporate thiol groups into chitosan (Ch) to enhance its water solubility and mucoadhesion characteristics. Here, the in situ forming hydrogel was successfully developed using the Schiff-based reaction, and its physio-chemical and antibacterial characteristics were examined. Borate BG was also incorporated in the generated hydrogel to promote angiogenesis and tissue regeneration at the wound site. Investigations of in vitro cytotoxicity assays demonstrated that the synthesised hydrogels showed good biocompatibility and promoted cell growth. These results inspired us to investigate the effectiveness of skin wound healing in a mouse model. On the backs of animals, two full-thickness wounds were created and treated utilising two different treatment conditions: (1) OCMC/tCh hydrogel, (2) OCMC/tCh/borate BG, and (3) control defect. The wound closure ratio, collagen deposition, and angiogenesis activity were measured after 14 days to determine the healing efficacy of the in situ hydrogels used as wound dressings. Overall, the hydrogel containing borate BG was maintained in the defect site, healing efficiency was replicable, and wound healing was apparent. In conclusion, we found consistent angiogenesis, remodelling, and accelerated wound healing, which we propose may have beneficial effects on the repair of skin defects.

Large-scale analysis of MicroRNA expression in motor neuron-like cells derived from human umbilical cord blood mesenchymal stem cells.

Motor neuron diseases such as spinal cord injuries and amyotrophic lateral sclerosis are known as the most common disorders worldwide. Using stem cells (e.g., human umbilical cord blood mesenchymal stem cells) is currently a potent medical approach for modulating the impact of neural damages and regeneration of spinal cord injuries. MicroRNAs (miRNA) are taken into account as principal regulators during differentiation. The miRNAs play a significant role in stem cell self-renewal and fate determination. There are few studies on how miRNAs regulate neural differentiation in stem cells. The purpose of this study is to explore miRNA profiles of CB-MSCs during differentiation into motor neuron-like cells. Human CB-MSCs were isolated and characterized using flow cytometry. Cell differentiation has been induced by combining retinoic acid (RA) and sonic hedgehog (Shh) in a two-step protocol for 14 days. Then, cell differentiation was confirmed by immunocytochemistry and flow cytometry. The miRNA was analyzed using Illumina/Solexa sequencing platform. In this regard, three libraries were prepared to investigate the effect of these two biological morphogens on the miRNA profile of the differentiating cells. These libraries were Control (non-treated CB-MSCs), Test 1 (RA + /Shh +), and Test 2 (RA-/Shh-). Quantitative RT-PCR was employed to verify miRNA expression. CB-MSCs were spindle-shaped in morphology, and they did not express hematopoietic markers. After differentiation, the cells expressed motor neuron markers (i.e., Islet-1, SMI-32, and ChAT) at the protein level after 14 days. The analysis of miRNA sequencing demonstrated a significant up-regulation of miR-9-5p and miR-324-5p in Test 1 (RA + /Shh +). Also, there is a considerable down-regulation of mir-137 and let-7b in Test 2 (RA-/Shh-). These results have been obtained by comparing them with the Control library. Indeed, they were responsible for neuron and motor neuron differentiation and suppression of proliferation in neural progenitor cells. Furthermore, significant up-regulation was detected in some novel microRNAs involved in cholinergic, JAK-STAT, and Hedgehog and MAPK signaling pathways. CB-MSCs are potent to express motor neuron markers. This procedure has been performed by developing a two-week protocol and employing Shh and RA. The miRNA profile analysis showed a significant up-regulation in the expression of some miRs involved in neuron differentiation and motor neuron maturation. MiR-9-5p and miR-324-5p were up-regulated at the early stage of differentiation. Also, miR-137 and miR-let-7b were downregulated in the absence of RA and Shh. Furthermore, several novel miRNAs involved in cholinergic, Hedgehog, MAPK, and JAK-STAT signaling pathways have been detected. However, further studies are still necessary to validate their functions during motor neuron generation and maturation.

The latest achievements in plant cellulose-based biomaterials for tissue engineering focusing on skin repair.

The present work reviews recent developments in plant cellulose-based biomaterial design and applications, properties, characterizations, and synthesis for skin tissue engineering and wound healing. Cellulose-based biomaterials are promising materials for their remarkable adaptability with three-dimensional polymeric structure. They are capable of mimicking tissue properties, which plays a key role in tissue engineering. Besides, concerns for environmental issues have motivated scientists to move toward eco-friendly materials and natural polymer-based materials for applications in the tissue engineering field these days. Therefore, cellulose as an appropriate substitute for common polymers based on crude coal, animal, and human-derived biomolecules is greatly considered for various applications in biomedical fields. Generally, natural biomaterials lack good mechanical properties for skin tissue engineering. But using modified cellulose-based biopolymers tackles these restrictions and prevents immunogenic responses. Moreover, tissue engineering is a quick promoting field focusing on the generation of novel biomaterials with modified characteristics to improve scaffold function through physical, biochemical, and chemical tailoring. Also, nanocellulose with a broad range of applications, particularly in tissue engineering, advanced wound dressing, and as a material for coupling with drugs and sensorics, has been reviewed here. Moreover, the potential cytotoxicity and immunogenicity of cellulose-based biomaterials are addressed in this review.

Synthesis and characterization of bacterial cellulose-based composites for drug delivery.

Bacterial cellulose (BC) was produced via the static fermentation process using G. xylinus. Cellulose and diethylaminoethyl cellulose (DEAEC) were converted to carboxymethyl cellulose (CMC) and carboxymethylated diethylaminoethyl cellulose (CMDEAEC) while to prepare the composites, two different methods were used: by either direct addition of the materials to the fermentation medium or addition of the materials after the fermentation process. Structural characteristics of composites were determined using instrumental techniques. Potential application of BC, BC/CMC, and BC/CMDEAEC in drug delivery system was examined using methylene blue (MB) as a model drug where the loading capacity and swelling ratio for the samples were as follows: BC/CMC > BC/CMDEAEC > BC. The result of the in-vitro study was in favor of the release behavior of BC/CMDEAEC composite. The MB loading data were fitted using Langmuir and Freundlich equations and kinetic behavior of the release was described by Higuchi and Korsmeyer-Peppas models.

Removal of Acid Brown 354 from wastewater by aminized cellulose acetate nanofibers: experimental and theoretical study of the effect of different parameters on adsorption efficiency.

Wastewater effluents usually involve dyes that are dangerous for aquatic life and other environments. Many of these dyes are toxic, carcinogenic, and can cause skin and eye irritation. In this study, firstly aminized cellulose acetate was prepared from cellulose acetate and applied for the adsorption of Acid Brown 354 from aqueous solutions. The effects of different parameters including adsorbent dosage, pH, temperature, and initial concentration of dye on adsorption capacity were examined. Results showed that removal efficiency of dye declined by increasing values of all parameters. Finally, maximum removal of dye was achieved in the presence of 0.1 g adsorbent, pH of 2, and 10 mg/L of initial dye concentration at a temperature of 25 °C. Also, different adsorption isotherms were investigated including Langmuir, Temkin, and Freundlich models and results demonstrated that the adsorption isotherm of dye followed the Freundlich model with a correlation coefficient of 0.988 revealing that the bond between the dye and the adsorbent is strong. Finally, kinetic study indicated that the adsorption of dye is exactly governed by pseudo-second-order kinetics explaining that the adsorption process is chemical and the adsorbent can not be reused.

Development of a cellulose-based scaffold for sustained delivery of curcumin.

Due to the unique properties of cellulose-based materials, they are attractive to be developed in industrial pharmaceutics and biomedical fields. Carboxymethyl-diethyl amino ethyl cellulose scaffold (CM-DEAEC) has been synthesized in the current work as a smart novel derivative of cellulose with a great functionality in drug delivery systems. The scaffolds were well cross-linked with 2% (v/v) epichlorohydrin (ECH), loaded with curcumin (Cur), and then were analyzed by FT-IR, XRD, SEM, and mechanical strength. While developing the ideal delivery platform, curcumin (an important chemotherapeutic agent) was chosen due to its hydrophobicity and poor bioavailability. Thus, we developed a novel scaffold for efficient loading and controlled releasing of curcumin. The swelling ratio of 136%, high curcumin entrapment efficiency (up to 83.7%), sustained in vitro drug release profile, and appropriate degradability in three weeks confirmed significant properties of the CM-DEAEC scaffold. More than 99% antibacterial activity has been observed by the cross-linked curcumin loaded CM-DEAEC scaffolds. Cytotoxicity studies using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 4',6-diamidino-2-phenylindole (DAPI) staining showed that cross-inked curcumin loaded CM-DEAEC scaffolds did not show any toxicity using L929 cells. All experiments were compared with CMC scaffolds and better characteristics of the novel scaffold for drug delivery have been confirmed.

Ratiometric visual detection of tetracycline residues in milk by framework-enhanced fluorescence of gold and copper nanoclusters.

We reported a novel dual-emission fluorescence probe fabricated by encapsulating both gold (AuNCs) and copper nanoclusters (CuNCs) into zeolitic imidazolate framework-8 (ZIF-8). Obtained composite (AuCuNCs@MOF) was utilized for ratiometric determination of Tetracycline (Tcy) antibiotic. Under excitation at 400 nm, the AuCuNCs@MOF composite displayed two emission peaks at 520 and 650 nm which were originated from AuNCs and CuNCs, respectively. Upon the addition of Tcy, the red emission intensity of the nanoparticles at 615 nm was significantly decreased, while the green emission at 520 nm stayed almost constant which resulted in a clear fluorescence color change from red to green under a UV lamp. The logarithm of the fluorescence ratio against the concentration of Tcy exhibited a satisfactory linear relationship from 20 to 650 nM with a detection limit (LOD) of 4.8 nM. Current probe was applied for Tcy quantification in milk samples with superior results.

Fabrication and evaluation of carboxymethylated diethylaminoethyl cellulose microcarriers as support for cellular applications.

Cellulose based microcarriers can be used in biomedical science as supports for cell adhesion and proliferation. However, to facilitate cell attachment to their surface, they require appropriate functional surface charge. Cell function such as adhesion and growth is increased on the modified surfaces with cationic and anionic groups. In this research, diethylaminoethyl cellulose was carboxymethylated to produce soluble multifunctional cellulose with simultaneous presence of cationic and anionic functional groups. Then, carboxymethylated diethylaminoethyl cellulose (CM-DEAEC) were produced by ionic crosslinking. Various instrumental techniques were applied to characterize the microcarriers. Biological tests were also performed to determine cell seeding efficiency, proliferation and attachment on microcarriers. Fabricated CM-DEAEC microcarriers had 1500-1800 µm diameter, +26.0 surface potential, 376% swelling behavior and 233 °C glass transition temperature respectively. The findings showed that CM-DEAEC microcarriers support cellular attachment and proliferation very well and hence are promising materials for cell therapy and tissue engineering applications.

Modification of Immobilized Titanium Dioxide Nanostructures by Argon Plasma for Photocatalytic Removal of Organic Dyes.

The aim of this study was to modify surface properties of immobilized rutile TiO2 using Argon cold plasma treatment and to evaluate the performance of the catalyst in photocatalytic elimination of synthetic dyes in UV/TiO2/H2O2 process. The surface-modified TiO2 was characterized by XRD, EDX, SEM, UV-DRS and XPS analyses. Response surface methodology was adopted to achieve high catalyst efficiency by evaluating the effect of two main independent cold plasma treatment parameters (exposure time and pressure) on surface modification of the catalyst. The increase of the plasma operation pressure led to higher decolorization percentage, while the increase of plasma exposure time decreased the decolorization efficiency. RSM methodology predicted optimum plasma treatment conditions to be 0.78 Torr and 21 min of exposure time, which resulted in decolorization of 10 mg/L solution of the malachite green solution by 94.94% in 30 min. The plasma treatment decreased the oxygen to titanium ratio and caused oxygen vacancy on the surface of the catalyst, resulting in the superior performance of the plasma-treated catalyst. Pseudo first-order kinetic rate constant for the plasma-treated catalyst was 4.28 and 2.03 times higher than the rate constant for the non-treated photocatalyst in decolorization of aqueous solutions of malachite green and crystal violet, respectively.

Evaluation of cellular attachment and proliferation on different surface charged functional cellulose electrospun nanofibers.

Fabrication and characterization of different surface charged cellulose electrospun scaffolds including cellulose acetate (CA), cellulose, carboxymethyl cellulose (CMC) and quaternary ammonium cationic cellulose (QACC) for biomedical applications have been reported in this research. Several instrumental techniques were employed to characterize the nanofibers. MTT assay and cell attachment studies were also carried out to determine the cytocompatibility, viability and proliferation of the scaffolds. Fabricated CA, cellulose, CMC and QACC nanofibers had 100-600 nm diameter, -9, -1.75, -12.8, + 22 mV surface potential, 2.5, 4.2, 7.2, 7 MPa tensile strength, 122, 320, 515, 482 MPa Young modules, 430, 530, 670 and 642% water uptake and 92°, 58°, 45°, 47° contact angle respectively. The findings showed that cell adhesion and proliferation is strongly enhanced on the modified surfaces with quaternary ammonium and carboxymethyl groups. We believe the use of cationic and anionic surface modified cellulose electrospun nanofibers presents promising materials for biomedical applications.

Ultrasonic mediated production of carboxymethyl cellulose: Optimization of conditions using response surface methodology.

In the present research the optimization of ultrasound-mediated production of carboxymethyl cellulose under microwave irradiation, towards achieving reduction of chemicals, time of reaction and energy was carried out. Cellulose was extracted and treated by environmentally friendly chlorine free bleaching method using hydrogen peroxide. Produced alpha-cellulose was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric/differential thermal analysis (TG/DTA). Response Surface Methodology (RSM) was used to optimize the preparation of carboxymethyl cellulose (CMC). Highest degree of substitution 0.74 was obtained at 240 W ultrasonic power for 37 min followed by etherification at 490 W microwave power for 12 min. Results show that the preparation of CMC from cotton linter using ultrasound and microwave energy can reduce the processing time, chemicals and energy consumption. Additionally, X-ray analysis shows that the ultrasonic energy is able to break cellulose crystals into smaller parts compared to other methods. SEM photographs showed that this treatment is able to remove impurities from raw material.

Use of enzymatic bio-Fenton as a new approach in decolorization of malachite green.

An enzymatic reaction using glucose oxidase was applied for in situ production of hydrogen peroxide for use in simultaneously Fenton's reaction in decolorization of malachite green. It was found that decolorization rate increased by increasing of glucose concentration from 0.2 g/L to 1.5 g/L. Decolorization rate showed different behaviors versus temperature changes. Initial rate of decolorization process was increased by increasing of temperature; after 30 minutes, especially at temperatures above 30 °C, the decolorization rate was gradually reduced. The pH value in the reaction media was decreased from natural to about pH = 3 which had synergic effect on the Fenton process by stabilizing of Fe(2+) ions.