Effect of pH variation on cross-linking of water-soluble and acid-soluble chitosan with sodium tripolyphosphate and gallium-67

Background: Chitosan is a cationic biopolymer obtained from deacetylating chitin, a naturally compoundpresent in crustacean shell, fungi and exoskeleton of insects. Chitosan has various applications including drug and gene delivery systems, wound dressing and as scaffolds for tissue engineering, agriculture, textile, food and feed nanotechnology, waste water treatments. chitosan-TPP particle figure out as the most important and stable nanoparticle for chitosan application in various fields. Objective: At this study chitosan was chemically modified by sodium tripolyphosphate (TPP). Afterward, TPP-chitosan was radiolabeled with gallium-67 radionuclide. The effect of several factors on labeling yield such as chitosan solubility, acidity and concentration of TPP-chitosansolution, incubation time with gallium-67 were investigated. Methods: To prepare [67Ga] gallium-chitosan complex, chitosan (0.5 ml) was dissolved in 2.2 mCi of [67Ga] gallium chloride solution. The obtained solution was stirred for 5 min and then was kept for 30 min at room temperature. Radiochemical purity and radiolabeling yield was measured via radiochromatography that it was performed by using a radio thin-layer chromatography (TLC) scanner instrument. To investigate the effect of chitosan kind and concentration on the labeling yield, two kinds of chitosan (acid-soluble chitosan and water-soluble chitosan) with two different concentrations (1% and 0.5%) at different pH were used. In addition, labeling efficiency and stability of the 67Ga-TPP-chitosan complex (acidic/water soluble chitosan) at both concentrations (0.5 and 1%) at room temperature was assessed for 30, 45 and 60 min. Results: The incubation time has not significant effect on labeling yield. The acidic soluble chitosan, which has highest radiolabeling yield at pH=9.3-10.4, water soluble chitosan showed the highest radiolabeling yields at pH > 5. Also, the prepared complex was stable in the final solution at room temperature and can even be used 24 hours after preparation for further application. Conclusion: Taken together, the TPP modified water soluble chitosan at concentration 0.5 % depicted the highest radiochemical yield (>95 %) at the optimized condition (pH= 6.2–7.6). Therefore, TPP modified water soluble chitosan can be an effective carrier for therapeutic radionuclides for tumor treatment.

Utilization of Gelling Polymer to Formulate Nanoparticles Loaded with Epalrestat-Cyclodextrin Inclusion Complex: Formulation, Characterization, In-Silico Modelling and In-Vivo Toxicity Evaluation

Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (β-CD) and sulfobutyl ether₇ β-CD (SBE7 β-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE7 β-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5–348.4 nm, with polydispersity index (PDI) ranging from 0.302–0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75–88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits.

Meat Substitution with Oat Protein Can Improve Ground Beef Patty Characteristics

The consumer acceptance of alternative plant-focused ingredients within the meat industry is growing globally. Oat protein is insoluble and used to increase product yield and fat retention. Furthermore, inclusion of oat protein can provide manufacturers another option for extending beef supplies. As the consumer diet shifts for improvements in nutritional density, oat protein is an alternative ingredient that lacks information on inclusion in a ground beef formulation. Coarse ground beef was allocated to one of four treatments, mixed with oat protein (0%, 1.5%, 3.5% and 4.5%), water, salt, pepper, textured vegetable protein, soy protein concentrate, and sodium tripolyphosphate. Meat blocks (n = 3 batches) were finely ground and formed into patties (N = 65/treatment). Patties were placed onto an expanded polystyrene tray, overwrapped with polyvinyl chloride film and displayed for 7 days. Instrumental color (L*, a*, and b*) decreased throughout simulated display (p = 0.0001). Increased usage rates of oat protein in patties resulted in greater cook yields (p = 0.0001). Objective measures of Allo-Kramer shear force values increased as oat protein inclusion rates increased (p = 0.0001). Oat protein can be incorporated in ground beef patties with positive effects on cook yield, but inclusion rate may have a deleterious impact on color and instrumental tenderness.

Formulation and Characterization of Chitosan Based Dexibuprofen Nanoparticles Using Ionotropic Gelation Method

Dexibuprofen is a pharmacologically active enantiomer of racemic ibuprofen (NSAID), which is used to treat pain and inflammation. Like common NSAIDs, Dexibuprofen is an active enantiomer of ibuprofen that suppresses the prostanoid synthesis in the inflammatory cells via inhibition of the COX-2 isoform of the arachidonic acid COX. The therapeutic use of Dexibuprofen is limited by the rapidity of the onset of its action and its short biological half-life. Hence, our aim was to develop Dexibuprofen nanoparticles formulation to overcome these disadvantages using optimized concentration of polymers by appropriate methods for nanoparticle preparation. The drug and the nanoparticle formulation of Dexibuprofen F11 were comparatively assessed for FT IR spectrums by using FT-IR method. The DSC study was used as one of the tool to assess the compatibility between drug and the excipients. As per DSC thermograms, the drug as well as drug with mixture of excipients chitosan, sodium tripolyphosphate had shown no interactions with dexibuprofen. The ionotropic gelation method was used to prepare Dexibuprofen nanoparticles. The chitosan and sodium tripolyphosphate (TPP) of different concentrations were used as polymers to prepare Dexibuprofen nanoparticles. Total eleven different formulations were explored with different concentrations of drug : polymer ratios using ionotropic gelation method to identify optimal concentrations of polymer. Among different formulations, F11 formulation with optimized concentration of 5% chitosan and 1% Sodium tripolyphosphate polymers along with Dexibuprofen showed maximum drug release. The objective was to evaluate the developed Dexibuprofen nanoparticles. In-vitro drug release was evaluated in 0.05M phosphate buffer pH7.2 and found that the drug release of F11 formulation of Dexibuprofen nanoparticle had shown release till 24 hours more than that of other trials. Hence, F11 formulation was considered as the optimized nanoparticle formulation to control drug release till 24 hours. The entrapment efficacy of the formulated Nanoparticles was found to be in the range of 75.48%-91.22% respectively.

Development of Gelatin/Misoprostol Compounds for Use in Pregnancy Failures

Early abortion is one of the most common complications during pregnancy. However, the frequent handling of the genital region, more precisely the vagina, which causes discomfort to patients in this abortion process due to the frequency of drug insertion, as four pills are inserted every six hours, has led to the search for alternatives to alleviate the suffering caused by this practice in patients who are already in a shaken emotional state. Hence, this work aimed to develop composites of gelatin and misoprostol, using a conventional single-dose drug delivery system. These composites were prepared by freeze/lyophilization technique, by dissolving the gelatin in distilled water, with a concentration of 2.5% (w/v), and misoprostol was incorporated into the gelatin solution at the therapeutic concentration (800 mcg). They were subsequently molded, frozen and lyophilized. The samples of the composites were then crosslinked with sodium tripolyphosphate (TPP) 1% (v/v) with respect to the gelatin mass for 5 min. The characterization techniques used were: Optical Microscopy (OM), Fourier Transformed Infrared Spectroscopy (FTIR), Thermogravimetry (TG), Swelling, Biodegradation and Cytotoxicity. In OM it was observed that the addition of the drug improved the cylindrical appearance of the compounds, in comparison with the sample that was composed of only gelatin. There was a reduction in the degree of swelling with the addition of the drug and crosslinking. The cytotoxicity test indicated the biocompatibility of the material. Based on the results obtained in these tests, the composites have therapeutic potential for uterine emptying in pregnancy failures, especially in the first trimester.

Dietary calcium to phosphorus ratio affects postprandial phosphorus concentrations in feline plasma

The impact of dietary phosphorus on chronic renal disease in cats, humans and other species is receiving increasing attention. As calcium (Ca) and phosphorus (P) metabolism are linked, the ratio of Ca:P is an important factor for consideration when formulating diets for cats and other animals. Here, we describe a fully randomized crossover study including 24 healthy, neutered adult cats, investigating post-prandial responses in plasma P, ionised Ca (iCa) and parathyroid hormone (PTH) following one meal (50% of individual metabolic energy requirement) of each of six experimental diets. Diets were formulated to provide P at either 0.75 or 1.5 g/1000kcal (4184kJ) from the soluble phosphorus salt sodium tripolyphosphate (STPP, Na5P3O10), variable levels of organic Ca and P sources, and an intended total Ca:P of ∼1.0, 1.5 or 2.0. For each experimental diet, baseline fasted blood samples were collected prior to the meal, and serial blood samples collected hourly for 6 hours thereafter. For all diets, a significant increase from baseline was observed at 120mins in plasma PTH (p<0.001). The diet containing the highest STPP inclusion level and lowest Ca:P induced the highest peaks in post-prandial plasma P and PTH levels (1.8mmol/l and 27.2pg/ml, respectively) and the longest duration of concentrations raised above baseline were observed at 3 hours for P and 6 hours for PTH. Data indicate that Ca:P modulates postprandial plasma P and PTH. Therefore, when formulating diets containing soluble P salts for cats, increasing the Ca:P ratio should be considered.