Efficient heterogeneous synthesis of nucleophilic carboxymethyl hydrazides of polysaccharides.

Nucleophilic moieties in polysaccharides (PS) with distinct higher reactivity compared with the hydroxy group are interesting for sustainable applications in chemistry, medicine, and pharmacy. An efficient heterogeneous method for the formation of such nucleophilic PS is described. Employing alcohols as slurry medium, protonated carboxymethyl (CM) PS and hydrazine hydrate are allowed to react at elevated temperatures. The CM derivatives of starch and pullulan can be transformed almost quantitatively to the corresponding hydrazides. The reaction is less efficient for CM dextrans and CM xylans. As slurry media, 2-propanol and ethanol were probed, and the results are compared with a homogeneous procedure performed in water. Overall, the heterogeneous procedure is superior compared with the homogeneous route. 2-Propanol is the best slurry medium investigated yielding PS hydrazides with the highest nitrogen content.

Expression, Purification and Characterization of CAR/NCOA-1 Tethered Protein in E. coli Using Maltose-Binding Protein Fusion Tag and Gelatinized Corn Starch.

The constitutive active/androstane receptor (CAR) is a nuclear receptor that functions as a xenobiotic sensor, which regulates the expression of enzymes involved in drug metabolism and of efflux transporters. Evaluation of the binding properties between CAR and a drug was assumed to facilitate the prediction of drug-drug interaction, thereby contributing to drug discovery. The purpose of this study is to construct a system for the rapid evaluation of interactions between CAR and drugs. We prepared recombinant CAR protein using the Escherichia coli expression system. Since isolated CAR protein is known to be unstable, we designed a fusion protein with the CAR binding sequence of the nuclear receptor coactivator 1 (NCOA1), which was expressed as a fusion protein with maltose binding protein (MBP), and purified it by several chromatography steps. The thus-obtained CAR/NCOA1 tethered protein (CAR-NCOA1) was used to evaluate the interactions of CAR with agonists and inverse agonists by a thermal denaturation experiment using differential scanning fluorometry (DSF) in the presence and absence of drugs. An increase in the melting temperature was observed with the addition of the drugs, confirming the direct interaction between them and CAR. DSF is easy to set up and compatible with multiwell plate devices (such as 96-well plates). The use of DSF and the CAR-NCOA1 fusion protein together allows for the rapid evaluation of the interaction between a drug and CAR, and is thereby considered to be useful in drug discovery.

Bio-Based Thermoplastic Starch Composites Reinforced by Dialdehyde Lignocellulose.

In order to improve the mechanical properties and water resistance of thermoplastic starch (TPS), a novel reinforcement of dialdehyde lignocellulose (DLC) was prepared via the oxidation of lignocellulose (LC) using sodium periodate. Then, the DLC-reinforced TPS composites were prepared by an extrusion and injection process using glycerol as a plasticizer. The DLC and LC were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM), and the effects of DLC content on the properties of the DLC/TPS composites were investigated via the evaluation of SEM images, mechanical properties, thermal stability, and contact angles. XRD showed that the crystallinity of the DLC decreased due to oxidation damage to the LC. SEM showed good dispersion of the DLC in the continuous TPS phase at low amounts of DLC, which related to good mechanical properties. The tensile strength of the DLC/TPS composite reached a maximum at a DLC content of 3 wt.%, while the elongation at break of the DLC/TPS composites increased with increasing DLC content. The DLC/TPS composites had better thermal stability than the neat TPS. As the DLC content increased, the water resistance first increased, then decreased. The highest tensile strength and elongation at break reached 5.26 MPa and 111.25%, respectively, and the highest contact angle was about 90.7°.

Effect of processing methods on xylitol-starch base co-processed adjuvant for orally disintegrating tablet application.

Orally disintegrating tablet (ODT) is a friendly dosage form that requires no access to water and serves as a solution to non-compliance. There are many co-processed adjuvants available in the market. However, there is no single product possesses all the ideal characteristics such as good compressibility, fast disintegration and good palatability for ODT application. The aim of this research was to produce a xylitol-starch base co-processed adjuvant which is suitable for ODT application. Two processing methods namely wet granulation and freeze drying were used to compare the characteristics of co-processed adjuvant comprising of xylitol, starch and crospovidone XL-10 mixed at various ratios. The co-processed excipients were compressed into ODT and physically characterized for powder flow, particle size, hardness, thickness, weight, friability, in-vitro disintegration time and in-situ disintegration time, lubricant sensitivity, dilution potential, Fourier transform infrared spectroscopy, scanning electronic microscopy and x-ray diffraction analysis. Formulation F6 was selected as the optimum formulation due to the fastest in-vitro (135.33±11.52 s) and in-situ disintegration time (88.67±13.56s) among all the formulations (p<0.05). Increase in starch component decreases disintegration time of ODT. The powder flow fell under the category of fair flow. Generally, it was observed that freeze drying method produced smaller particle size granules compared to wet granulation method. ODT produced from freeze drying method had shorter disintegration time compared to ODT from wet granulation batch. In conclusion, a novel co-processed excipient comprised of xylitol, starch and crospovidone XL-10, produced using freeze drying method with fast disintegration time, good compressibility and palatability was developed and characterized. The co-processed excipient is suitable for ODT application.

Grafting from Starch Nanoparticles with Synthetic Polymers via Nitroxide-Mediated Polymerization.

Nitroxide-mediated polymerization (NMP) is employed to graft synthetic polymers from polysaccharides. This work demonstrates the first successful polymer grafting from starch nanoparticles (SNPs) via NMP. To graft synthetic polymers from the SNPs' surface, the SNPs are first functionalized with 4-vinylbenzyl chloride prior to reaction with BlocBuilder MA yielding a macroinitiator. Methyl methacrylate with styrene, acrylic acid, or methyl acrylate are then grafted from the SNPs. The polymerizations exhibited linear reaction kinetics, indicating that they are well controlled. Thermal gravimetric analysis and spectroscopic techniques confirmed the synthesis of the precursors materials and the success of the grafting from polymerizations. The incorporation of hydrophobic synthetic polymers on hydrophilic SNPs yields new hybrid materials that could find use in several industrial applications including paper coatings, adhesives, and paints.

Bulk Freeze-Drying Milling: a Versatile Method of Developing Highly Porous Cushioning Excipients for Compacted Multiple-Unit Pellet Systems (MUPS).

The compaction of multiple-unit pellet system (MUPS) is a challenging process due to the ease of coat damage under high compression pressure, thereby altering drug release rates. To overcome this, cushioning excipients are added to the tablet formulation. Excipients can be processed into pellets/granules and freeze-dried to increase their porosity and cushioning performance. However, successful formation of pellets/granules has specific requirements that limit formulation flexibility. In this study, a novel top-down approach that harnessed bulk freeze-drying milling was explored to avoid the challenges of pelletization/granulation. Aqueous dispersions containing 20%, w/w hydroxypropyl methylcellulose (HPMC), partially pregelatinised starch or polyvinylpyrrolidone alone, and with lactose (Lac) in 1:1 ratio, were freeze-dried and then milled to obtain particulate excipients for characterization and evaluation of their cushioning performance. This study demonstrated that bulk freeze-drying milling is a versatile method for developing excipients that are porous and directly compressible. The freeze-drying process modified the materials in a unique manner which could impart cushioning properties. Compared to unprocessed excipients, the freeze-dried products generally exhibited better cushioning effects. The drug release profile of drug-loaded pellets compacted with freeze-dried Lac-HPMC excipients was similar to that of the uncompacted drug-loaded pellets (f 2 value = 51.7), indicating excellent cushioning effects. It was proposed that the specific balance of brittle and plastic nature of the freeze-dried Lac-HPMC composite conferred greater protective effect to the drug-loaded pellets, making it advantageous as a cushioning excipient.

Development and Optimization of a Starch-Based Co-processed Excipient for Direct Compression Using Mixture Design.

The development of novel excipients with enhanced functionality has been explored using particle engineering by co-processing. The aim of this study was to improve the functionality of tapioca starch (TS) for direct compression by co-processing with gelatin (GEL) and colloidal silicon dioxide (CSD) in optimized proportions. Design of Experiment (DoE) was employed to optimize the composition of the co-processed excipient using the desirability function and other supporting studies as a basis for selecting the optimized formulation. The co-processed excipient (SGS) was thereafter developed by the method of co-fusion. Flow and compaction studies of SGS were carried out in comparison to its parent component (TS) and physical mixture (SGS-PM). Tablets were prepared by direct compression (DC) containing ibuprofen (200 mg) as a model for poor compressibility using SGS, Prosolv®, and StarLac® as multifunctional excipients. The optimized composition of SGS corresponded to TS (90%), GEL (7.5%), and CSD (2.5%). The functionality of SGS was improved relative to SGS-PM in terms of flow and compression. Tablets produced with SGS were satisfactory and conformed to USP specifications for acceptable tablets. SGS performed better than Prosolv® in terms of disintegration and was superior to StarLac with respect to tensile strength and disintegration time. The application of DoE was successful in optimizing and developing a starch-based co-processed excipient that can be considered for direct compression tableting.

Application of iodinated starch powder using an atomizer spray gun - a new and effective tool to evaluate hypohidrosis.

BACKGROUND: Hypohidrosis is defined as diminished sweating in response to an appropriate thermal or sympathetic stimulus. When encountered in a clinical setting, it necessitates an accurate documentation of its pattern and extent to prognosticate the risk of associated heat-related illnesses. This can be achieved by thermoregulatory sweat testing which includes a starch-iodine sweat test that can be administered via various methods. OBJECTIVE: To describe and evaluate the effectiveness and safety of a novel method of using an atomizer spray gun in administering the starch-iodine test. METHODS: We describe the administration of the starch-iodine test via an atomizer spray gun (Series 700 Lab Model; Mitsuba Systems, Mumbai, India). The method was utilized for the evaluation of 30 individuals who presented with symptoms of hypohidrosis. RESULTS: Application of iodinated starch powder prepared in-house with the atomizer spray gun achieved a lightweight and homogeneous coat on our patients' skin which allowed for clear visualization of the sweating pattern in areas of anhidrosis. The sharp demarcation of the pathological regions enabled the precise calculation of the affected body surface area of impaired sweating. Unlike the starch-iodine tests using the Minor and Wada methods, neither staining of the skin nor irritation was detected in this method. CONCLUSION: We report a novel method of using an atomizer spray gun to perform the starch-iodine test in a rapid, reproducible, effective, and safe manner suitable for use in the clinical evaluation of hypohidrosis.

Crosslinked Porous Starch Particles--a Promising Carrier.

UNLABELLED: Background. Starch is one of the most potential natural polymers used for various bio applications. Literature reports a num- ber of modification strategies such as physical, chemical, enzymatic and genetic to enhance the positive attributes and iron out the undesired features of neat starch. OBJECTIVES: To synthesize a crosslinked porous starch (CPS) as an efficient cargo for the delivery of calcium carbonate in an efficiently controlled manner for the treatment of hyperphosphatemia. MATERIAL AND METHODS: The CPS carrier was synthesized using a natural crosslinker, malic acid. The drug delivery system was formulated, followed by the in situ loading of calcium carbonate during the preparation of the CPS. The developed system was characterized with respect to FTIR, DSC, SEM, moisture content, zeta potential, encapsulation efficiency, phosphate binding efficiency and dissolution studies. RESULTS: The developed formulation was observed to deliver calcium carbonate in an enterically controlled manner. The binding of calcium to phosphate was established to be pH dependent and efficient at pH 7. The moisture content of CPS was in the range of 0.2-0.8%. The zeta potential of the colloidal system was noted to be sufficiently high, indicating the stability. The encapsulation efficiency of CPS particles for calcium was found to be 88-96%. CONCLUSIONS: An efficient, cost-effective, facile and commercially-viable formulation was demonstrated to deliver calcium carbonate for the treatment of hyperphosphatemia.

Amphiphilic graft copolymers from end-functionalized starches: synthesis, characterization, thin film preparation, and small molecule loading.

End-functionalized macromolecular starch reagents, prepared by reductive amination, were grafted onto a urethane-linked polyester-based backbone using copper-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry to produce novel amphiphilic hybrid graft copolymers. These copolymers represent the first examples of materials where the pendant chains derived from starch biopolymers have been incorporated into a host polymer by a grafting-to approach. The graft copolymers were prepared in good yields (63-90%) with high grafting efficiencies (66-98%). Rigorous quantitative spectroscopic analyses of both the macromolecular building blocks and the final graft copolymers provide a comprehensive analytical toolbox for deciphering the reaction chemistry. Due to the modular nature of both the urethane-linked polyester synthesis and the postpolymerization modification, the starch content of these novel hybrid graft copolymers was easily tuned from 28-53% (w/w). The uptake of two low molecular weight guest molecules into the hybrid polymer thin films was also studied. It was found that binding of 1-naphthol and pterostilbene correlated linearly with amount of starch present in the hybrid polymer. The newly synthesized graft copolymers were highly processable and thermally stable, therefore, opening up significant opportunities in film and coating applications. These results represent a proof-of-concept system for not only the construction of starch-containing copolymers, but also the loading of these novel polymeric materials with active agents.

Preparation of calcium- and magnesium-fortified potato starches with altered pasting properties.

Calcium- and magnesium-fortified potato starches were prepared by immersion in various concentrations of CaCl2 and MgCl2 aqueous solutions, respectively. The pasting properties, i.e., peak viscosity and breakdown, of all the starches obtained above were analyzed using a Rapid Visco Analyzer. Furthermore, the gelatinization properties and in vitro digestibility of the representative calcium- and magnesium-fortified starches were tested. The maximum calcium content of the fortified potato starches was as high as 686 ppm with the addition of a high-concentration CaCl2 solution, while the calcium content of the control potato starch was 99 ppm. The magnesium content increased from 89 to 421 ppm by treatment of the potato starch with an MgCl2 solution. Markedly lower values of peak viscosity and breakdown were observed in calcium- and magnesium-fortified potato starches than in the control potato starch. However, the gelatinization temperature and enthalpy as well as resistant starch content of calcium- and magnesium-fortified potato starches were similar to those of the control potato starch. It is concluded that potato starches with altered pasting properties can be easily manufactured by the use of solutions containing high levels of calcium and magnesium.

Organic synthesis of maize starch-based polymer using Rhizopus oryzae lipase, scale up, and its characterization.

The industrial utilization of native starches is limited because of their inherit nature, with characteristics such as water insolubility and their tendency to form unstable pastes and gels. In this investigation, a lipase produced from Rhizopus oryzae was used for modification of maize starch with palmitic acid at a reaction temperature of 45°C for 18 hr in the presence of dimethyl sulfoxide (DMSO). The synthesis of maize starch palmitate was confirmed by Fourier-transform infrared (FT-IR) and (1)H-nuclear magnetic resonance (NMR) spectra with a higher degree of substitution (DS) of 1.68. Thermal gravimetric analysis (TGA) showed that the maize starch palmitate is more stable even up to 496°C as compared to unmodified maize starch (231.4°C). Maize starch palmitate possesses high degree of substitution and thermal properties and thus can be widely used in food and pharmaceutical industry.

Removal of transition metal ions from aqueous solution using dialdehyde phenylhydrazine starch as adsorbent.

Dialdehyde phenylhydrazine starch (DASPH) was synthesized by reacting dialdehyde starch (DAS) with phenylhydrazine (PH) and it was characterized by Brunauer-Emmett-Teller (BET), scanning electron microscope, Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) techniques. FT-IR of DASPH revealed the incorporation of the Schiff Base group (C = N) group and the disappearance of the C = O (carbonyl) group. The adsorption behaviors of transition metal ions (Cd(2+), Zn(2+), Pb(2+) and Cu(2+)) were investigated as a function of pH and adsorption time. The results indicated that pH 5.0 and 120 min were the optimal conditions. Experimental results revealed that the maximum adsorption capacity of DASPH for the four transition metal ions was as follows: Cd(2+) (4.9 mmol/g) > Zn(2+) (3.3 mmol/g) >Pb(2+) (1.7 mmol/g) >Cu(2+) (0.83 mmol/g). In addition, the regeneration method of DASPH was also studied.

Synthesis and cytotoxicity evaluation of novel acylated starch nanoparticles.

Starch nanoparticles (StNPs) were acylated under ambient conditions to obtain various nanosized derivatives formed stable suspension in water and soluble in organic solvents. The degree of substitution (DS) was determined using (1)H NMR technique. The cytotoxicity potential of the derivatised StNPs was evaluated in mouse embryonic fibroblast (3T3L1) cells and A549 tumor cell line using MTT cell viability assay. Other parameters that determine the oxidative stress viz., reactive oxygen species (ROS) generation, intracellular reduced glutathione (GSH), superoxide generation and acridine orange/ethidium bromide staining were also investigated. The present study led to the conclusion that cytotoxic activity of acylated starch nanoparticles was dependent on their dosage, DS and type of substitution. The non-toxic nature in non-cancerous cells reveals that the nanoparticles (NPs) can be used for cancer therapy and drug delivery. The nanoparticles also offered reasonable binding propensity with CT-DNA.

Preparation and adsorption properties of dialdehyde 8-aminoquinoline starch.

Dialdehyde 8-aminoquinoline starch (DASQA) was synthesized by the reaction of dialdehyde starch (DAS) and 8-aminoquinoline and was used to adsorb various ions from aqueous solution. DASQA was characterized by Fourier transform infrared (FT-IR) spectra, thermogravimetric analysis, X-ray diffraction analysis. The adsorption properties of the polymer for Pb(2+), Cu(2+), Cd(2+), Ni(2+), and Zn(2+) were investigated. The result of the experiment reveals that the adsorption for Cd(2+) and Zn(2+)were approximately 2.51 mmol/g, 2.17 mmol/g, followed by Pb(2+) 1.93 mmol/g, Ni(2+) 1.66 mmol/g, Cu(2+) 1.19 mmol/g. Furthermore, the kinetic experiments indicated that the adsorption of DASQA for the above metal ions achieved equilibrium within 2 h. Therefore, DASQA is an effective adsorbent for the removal of different heavy metal ions from industrial waste solutions.

Synthesis of the starch grafting of superabsorbent and high oil-absorbing resin.

The graft copolymerization of the starch and acrylic were used to prepare the superabsorbent, and the high oil-absorbing resin was also studied preliminarily. In addition, following the method of the emulsion polymerization, the cerium nitrate amine was regarded as the initiator, the acrylic amide and the methyl methacrylate functioned as the monomer. There are several significant parameters taken into consideration such as the factors that influence the performance of the superabsorbent and the high oil-absorbing resin, the dosage of the initiator amount, the ratio of the starch and the monomer and the dosage of crosslinking agent.

Starch-quercetin conjugate by radical grafting: synthesis and biological characterization.

A novel flavonoid-polysaccharide conjugate was synthesized by free radical grafting of quercetin on starch. The covalent insertion of quercetin in the polymeric chain was confirmed by FT-IR, DSC and fluorescence analyses, while an estimation of the amount of quercetin bound per g of polymer was obtained by the Folin-Ciocalteu assay. The conjugate shows improved UV stability and retains the antioxidant properties of free quercetin, such as scavenging activity towards free radicals (DPPH and peroxynitrite); inhibition of the free radical formation (peroxidation of linoleic acid) and total antioxidant activity. The conjugate also prevented drug degradation and shows potential health functionality in the treatment of Alzheimer disease, diabetes and as skin-whitening agent.

Synthesis, characteristics, and applications of modified starch nanoparticles: A review.

Nowadays, starch nanoparticles (SNPs) are drawing attention to the scientific community due to their versatility and wide range of applications. Although several works have extensively addressed the SNP production routes, not much is discussed about the SNPs modification techniques, as well as the use of modified SNPs in typical and unconventional applications. Here, we focused on the SNP modification strategies and characteristics and performance of the resulting products, as well as their practical applications, while pointing out the main limitations and recommendations. We aim to guide researchers by identifying the next steps in this emerging line of research. SNPs esterification and oxidation are preferred chemical modifications, which result in changes in the functional groups. Moreover, additional polymers are incorporated into the SNP surface through copolymer grafting. Physical modification of starch has demonstrated similar changes in the functional groups without the need for toxic chemicals. Modified SNPs rendered differentiated properties, such as size, shape, crystallinity, hydrophobicity, and Zeta-potential. For multiple applications, tailoring the aforementioned properties is key to the performance of nanoparticle-based systems. However, the number of studies focusing on emerging applications is fairly limited, while their applications as drug delivery systems lack in vivo studies. The main challenges and prospects were discussed.

Production of starch with antioxidative activity by baking starch with organic acids.

A starch ingredient with antioxidative activity, as measured by the DPPH method, was produced by baking corn starch with an organic acid; it has been named ANOX sugar (antioxidative sugar). The baking temperature and time were fixed at 170 °C and 60 min, and the organic acid used was selected from preliminary trials of various kinds of acid. The phytic acid ANOX sugar preparation showed the highest antioxidative activity, but the color of the preparation was almost black; we therefore selected L-tartaric acid which had the second highest antioxidative activity. The antioxidative activity of the L-tartaric acid ANOX sugar preparation was stable against temperature, light, and enzyme treatments (α-amylase and glucoamylase). However, the activity was not stable against variations in water content and pH value. The antioxidative activity of ANOX sugar was stabilized by treating with boiled water or nitrogen gas, or by pH adjustment.

Oxidation of phenol by hydrogen peroxide catalyzed by metal-containing poly(amidoxime) grafted starch.

Polyamidoxime chelating resin was obtained from polyacrylonitrile (PAN) grafted starch. The nitrile groups of the starch-grafted polyacrylonitrile (St-g-PAN) were converted into amidoximes by reaction with hydroxylamine under basic conditions. The synthesized graft copolymer and polyamidoxime were characterized by FTIR, TGA and elemental microanalysis. Metal chelation of the polyamidoxime resin with iron, copper and zinc has been studied. The produced metal-polyamidoxime polymer complexes were used as catalysts for the oxidation of phenol using H(2)O(2) as oxidizing agent. The oxidation of phenol depends on the central metal ion present in the polyamidoxime complex. Reuse of M-polyamidoxime catalyst/H(2)O(2) system showed a slight decrease in catalytic activities for all M-polyamidoxime catalysts.