Greater Storage Stability Research Articles

Supersaturating drug delivery systems containing fixed-dose combination of two antihypertensive drugs: Formulation, in vitro evaluation and molecular metadynamics simulations

The purpose of this study was to associate the poorly water-soluble antihypertensive drugs candesartan cilexetil (CC) and hydrochlorothiazide (HCTZ) as fixed-dose combination, in the form of ternary Amorphous Solid Dispersions (ASD), using hydroxypropylmethylcellulose acetate succinate (HPMCAS) type M as polymeric carrier. The potential of the system to generate and to maintain supersaturation of both drugs was also evaluated. The ASDs were prepared by ball milling technique and solid-state characterization was performed by differential scanning calorimetry (DSC), Fourier transformed infrared spectroscopy (FTIR) and X-ray powder diffraction (XRPD). Interaction between drugs and polymer in solid-state was evaluated by molecular metadynamics simulations. In vitro supersaturation profiles were determined in biorelevant medium. Physicochemical stability of ASDs was also evaluated under different storage conditions. Amorphization of both drugs was confirmed by solid-state characterization techniques. Molecular metadynamics simulations indicated that CC has stronger interaction with HMPCAS than HCTZ. In vitro supersaturation studies have shown that ternary ASDs could generate and maintain supersaturation of both drugs in biorelevant medium. The polymer reduced the desupersaturation of both drugs. Ternary ASDs also showed physicochemical stability over a period of 90 days, demonstrating the potential of the polymer in reducing the drugs recrystallization over the time. Ternary ASDs of CC, HCTZ and HPMCAS can be considered a promising system to associate the drugs as fixed-dose combinations. Also, these systems generate and maintain supersaturation of both drugs in biorelevant medium, with great storage stability. HPMCAS M was a good carrier for reducing the desupersaturation of associated HCTZ and CC.

Folic acid-functionalized niosomal nanoparticles for selective dual-drug delivery into breast cancer cells: An in-vitro investigation

In this study, a folic acid-functionalized niosome was formulated and loaded with letrozole and curcumin as a promising drug carrier system for chemotherapy of the breast cancer cells. The formulation process was optimized by varying the type of Span 80 and total lipid to drug ratio, where Span 80 and lipid to drug molar ratio of 10 resulted in the niosomes with maximum encapsulation of both drugs but minimum size. The developed niosomal formulation showed a great storage stability up to one month with the small changes in drug encapsulation efficiency and size during the storage. In addition, they showed a pH-dependent release behaviour with slow drug release at physiological pH (7.4) while considerable drug release in acidic conditions (pH = 3), making it a promising candidate for breast cancer treatment. The cytotoxicity study shows the niosomal formulation has high biocompatibility with HEK-293 healthy cells, while having remarkable inhibitory effects on MCF-7 and MDA-MB-231 breast cancer cells due to the presence of folic acid in formulation, and in turn, selective internalization of the as-developed nanocarrier through folate receptor-mediated endocytosis. The double drug-loaded niosomes affect the gene expression by studied breast cancer cell lines; down-regulates the expression of Bcl2, cyclin D, and cyclin E genes while they up-regulate the expression of p53, Bax, caspase-3, and caspase-9 genes. The flow cytometry results showed that letrozole/curcumin-loaded niosomes enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cells compared to the mixture of letrozole and curcumin, which was due to the synergic effect between the two drugs as well as higher cell uptake by niosomal formulation. The findings of our study show the importance of developing highly biocompatible niosomal formulations in the future of nanomedicine that enables the co-delivery of two hydrophobic drugs into the cancer cells improves the efficiency of chemotherapy due to the synergic effect between the drugs.

Characterization and technological properties of peach palm (Bactris gasipaes var. gasipaes) fruit starch

Peach palm fruit mesocarp (Bactris gasipaes var. gasipaes) is already consumed in the Northern region of Brazil, after its cooking and is known as a source of starch and carotenoids and like all fruits it has low storage stability. This work characterized the starch extracted from the mesocarp of peach palm fruit using with water in terms of its physical and chemical properties. The SEM micrographs show that starch presented bimodal distribution (size 3.9–10.4 µm), while the smaller granules had a smooth surface and an oval or conical shape, the larger granules were spherical with holes and cracks on the surface. The starch presented low amylose content (<20%) and amylopectin branch chain length distribution with the absence of a shoulder, which is suggestive of perfect crystalline structure, and a higher proportion of medium chains (DP 13–24), despite the large number of short chains (DP 6–12), and on average DP 21. X-ray diffraction showed a mixture of polymorphs A and B, which can be considered C-type crystalline pattern, which is indicative of being a slow digestible starch. Through paste viscosity results, by RVA, we can observe low values for thermal and pasting properties, suggesting greater homogeneity of crystals. Also, due to interaction with lipids originally present (2.69%), the starch showed lower retrogradation rate (22.64%), which resulted in a weak gel after 24 h of storage. As a product with greater storage stability, peach palm fruit starch, extracted for the purpose of promoting its regional use, has shown that it can be used in products where slow and smooth retrogradation is desired, such as in breads, soups, chowder and porridges, without the use of emulsifiers or fat.

Optimized doxycycline-loaded niosomal formulation for treatment of infection-associated prostate cancer: An in-vitro investigation

Developing drug delivery systems with both antibacterial and anti-cancer effects is of importance in the treatment process of infection-associated cancers, especially prostate cancer. In this study, Span 60, Tween 60, and cholesterol were used to formulate doxycycline-loaded niosomes as a promising drug carrier system as either antibacterial or anticancer formulation. The formulation process was optimized by multi-objective response surface methodology (RSM), and then characterized. The developed niosomal formulation showed great storage stability for up to 2 weeks. In addition, they showed remarkable drug release in acidic solution (pH = 3) compared with physiological pH (7.4). The in-vitro performances of the as-developed niosomal formulations were investigated for two different applications: antibacterial and anticancer. The antibacterial properties of doxycycline-loaded niosome were investigated using different Gram-negative, and Gram-positive bacteria, where considerable (50–75%) decreases in MIC values were observed. Moreover, the niosomal formulation also possessed promising chemotherapy effects against prostate cancer cells (PC3) but enhanced biocompatibility against normal HEK293 cells. The enhanced chemotherapy effect was correlated to the regulation of different genes as well as changes in cell cycle of PC3 cells after treatment with the niosomal formulation. These carriers could be served as a potential drug delivery system for the treatment of prostate cancer.

Synthesis and Characterization of Cationic Waterborne Epoxy Acrylic Resin

In this work, a cationic waterborne epoxy acrylic resin (WCEA) was synthesized from bisphenol an epoxy resin, acrylic acid, acrylic acid, hydroquinone as an inhibitor, and N, N-dimethylbenzylamine (DMBA) as a catalyst. The changes of NCO groups and acid value during the synthesis process were measured by chemical titration method, and its Fourier Transform Infrared (FTIR) spectra were investigated. The results indicate that the acidified waterborne resin has great water solubility and storage stability after grafting the half-blocked isocyanate.

β-Cyclodextrin-Immobilized Ni/Graphene Electrode for Electrochemical Enantiorecognition of Phenylalanine.

In this work, a Ni/graphene (Ni/G) electrode was designed and fabricated by plasma-enhanced chemical vapor deposition (PECVD) for the ultrasensitive recognition of d- and l-phenylalanine. Through a single-step PECVD process, the Ni/G electrode can achieve better hydrophilicity and larger catalytic surface area, which is beneficial for the electrochemical recognition of bio-objects. After surface modification with β-cyclodextrin, the Ni/G electrode can distinguish d-phenylalanine from l-phenylalanine according to a 0.09 V peak shift in differential pulse voltammetry tests. Moreover, this Ni/G electrode achieved a detection limit as low as 1 nM and a wide linear range from 1 nM to 10 mM toward l-phenylalanine, with great storage stability and working stability.

Low-intensity light-induced drug release from a dual delivery system comprising of a drug loaded liposome and a photosensitive conjugate

This study reports the development of a binary drug delivery system consisting of charged liposomes and an oppositely charged peptide–photosensitiser conjugate. Liposomes were prepared with phosphatidyl-l-serine as a negatively charged lipid. Calcein, a fluorophore marker, and doxorubicin, an anticancer drug, were used as model hydrophilic loads. The conjugate consisted of a positively charged arginine-rich peptide synthesised by solid-phase peptide synthesis, and a phthalocyanine derivative with characteristic absorption around 685 nm. Illumination of the binary system with far-red light of 12–15 mW/cm2 intensity resulted in 5- to 15-fold increase in release of payloads from the liposomes. The mechanism of drug release was based on photosensitised oxidation of lipids destabilising the liposomal membrane. The cytotoxicity of the liposomes loaded with doxorubicin was tested on B16-F10 melanoma and Y79 retinoblastoma cells. The cytotoxicity of the illuminated binary system in melanoma cell line was significantly higher as compared to the system without illumination. The components of the binary system can be individually prepared and stored with greater storage stability. However, their combination will allow for substantial release of hydrophilic payload from the liposomes under externally applied light.

Self-assembled composite nanoparticles based on zein as delivery vehicles of curcumin: role of chondroitin sulfate.

Composite nanoparticles composed of zein and chondroitin sulfate (CS) were self-assembled by the method of antisolvent precipitation to deliver curcumin (ZCCNPs). The structure of ZCCNPs changed from spheres to microaggregates with the increase of CS, involving hydrogen bonding and electrostatic and hydrophobic effects. The resistance of ZCCNPs to degeneration was improved by CS. The encapsulation efficiency of curcumin was enhanced by CS and showed the maximum (91.97%) when the mass ratio of zein-to-CS was 1 : 1 (ZCCNPs1:1). The crystallinity of curcumin changed to amorphous in ZCCNPs1:1. ZCCNPs1:1 exhibited great stability at pH 3.0-8.0, and it showed excellent thermostability at 35, 55, and 80 °C respectively for 120 min when the pH was 4.0 or 6.0. Meanwhile, it showed great storage stability at 4 and 22 °C respectively for 30 days. The retention rate of curcumin in ZCCNPs1:1 was higher than 65% within 8 days. The presence of CS improved the antiproliferative activity of curcumin-loaded zein nanoparticles (Cur-ZNPs) to HCT116 cells. ZCCNPs1:1 exhibited higher bioaccessibility (42.36%) than Cur-ZNPs. In addition, ZCCNPs1:1 exhibited excellent biocompatibility evaluated using in vitro cytotoxicity assay on NCM460 cells. The studies indicate that the delivery system fabricated in our work would be efficient for improving the application of hydrophobic nutrients in functional foods.

Preparation, physicochemical properties, in vitro evaluation and release behavior of cephalexin-loaded niosomes.

In this study, optimized cephalexin-loaded niosomal formulations based on span 60 and tween 60 were prepared as a promising drug carrier system. The niosomal formulations were characterized using a series of techniques such as scanning electron microscopy, Fourier transformed infrared spectroscopy, dynamic light scattering, and zeta potential measurement. The size and drug encapsulation efficiency are determined by the type and composition of surfactant. The developed niosomal formulations showed great storage stability up to 30 days with low change in size and drug entrapment during the storage, making them potential candidates for real applications. Moreover, the prepared niosomes showed negligible cytotoxicity for HepG2 cells, measured by MTT assay. The antibacterial properties of cephalexin-loaded niosome were investigated using S. aureus and E. coli as gram-positive and gram-negative bacteria, respectively. The results showed that the encapsulation of antibiotic drug in niosomal formulation could enhance the antibacterial efficiency of the drug, where the minimum inhibitory concentration was droped from 8 µg/mL (cephalexin) to 4 µg/mL (cephalexin-loaded niosome) and from 4 µg/mL (cephalexin) to 1 µg/mL (cephalexin-loaded niosome) against E. coli and S. aureus, respectively. The findings of our study show that the improvement of cephalexin bioavailability and prolonged drug release profile could be obtained by niosomal formulation as a favorable antibiotic drug delivery system.

Graphene oxide as a polymeric N-halamine carrier and release platform: Highly-efficient, sustained-release antibacterial property and great storage stability.

N-halamine compounds have been applied as antibacterial agents owing to the oxidative chlorine. In this work, graphene oxide (GO) as carrier was used to load N-halamine compounds for the sustained-release of chlorine in order to maintain long-term biocidal efficacies. 3‑(3'‑Acrylic acid propylester)‑5,5‑dimethylhydantoin (APDMH) was synthesized using 5,5‑dimethylhydantoin as a heterocyclic precursor and attached on the surface of GO nanosheets via in-situ polymerization. The modified GO composites were characterized by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The chlorinated GO nanosheets modified with polymerized APDMH (PAPDMH) were very stable and possessed long-term antibacterial properties. The GO-PAPDMH-Cl composites exhibited good antimicrobial efficacies against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli O157:H7) with log reductions of 7.20 and 7.06 within 30 min of contact time, respectively.

Comparison of laboratory performance of two superpave binders mixed with two modifiers

This research compares laboratory performance of two superpave modified asphalt binders including PG 64-10 and PG 70-10. A series of laboratory tests were conducted on 14 asphalt mixes treated with 0, 2, 4, and 6% of Acrylate Styrene Acrylonhrtilrei (ASA) polymer and nanoparticles aluminium oxide (Al2O3) by weight of the base asphalt binder.It was found that as the concentration of both modifiers increased, the resistance of asphalt binder PG 64-10 and PG 70-10 to rutting parameter and fatigue parameter increased for concentrations of 2 and 4% only. Increases in complex modulus values were consistently observed for all modified asphalt binders compared to the base asphalt binder. The increment of concentration of ASA polymer and Al2O3 nanoparticles can significantly increase the asphalt binder viscosity. All modified asphalt samples have greater storage stability at high temperatures. Also, it was found that the adding of ASA polymer and Al2O3 nanoparticles to all the mixes results in a substantial impact on the material properties of the asphalt binder. The samples altered with Al2O3 nanoparticles show better results than the samples modified with ASA polymer. The figure of 4% can be considered the optimum amount for both modifiers.

Eugenol-chitosan nanoemulsions by ultrasound-mediated emulsification: Formulation, characterization and antimicrobial activity

Eugenol is widely used in food industries where it encounters major concerns such as its poor solubility and stability. Herein, a novel eugenol-nanoemulsion was prepared by using ultrasonication as emulsification techniques, chitosan nanoparticle as carrier, and surfactant, as emulsifier. The results indicated that droplet size and encapsulation efficiency of the nanoemulsions was significantly affected by testing factors. The selected parameters for nanoemulsions were determined as chitosan-eugenol ratio of 1:1, Tween20 1 wt/v%, ultrasonic power 450 W and ultrasonic time 6 min. The nanoparticles were performed in regularly spherical shape distributed within 80–100 nm. Besides, the nanoemulsions showed great storage stability and thermal stability and the nanoeparticles performed excellent antioxidant capacity, antimicrobial activity as well as an initial burst of eugenol followed by plateau. Therefore, eugenol-chitosan nanoemulsions had great potential in food formulations for extending the shelf life.

Evaluation of elevated temperature properties of asphalt cement modified with aluminum oxide and calcium carbonate nanoparticles

Higher temperature properties of the asphalt cement have been characterized before and after modification using dynamic shear rheometer (DSR) and viscosity testing. In this study, calcium carbonate nanoparticles (CaCO3) and aluminum oxide nanoparticles (Al2O3) have been added to the base asphalt cement with concentrations of 3, 5 and 7%.wt by the weight of the asphalt cement. The increase of CaCO3 and Al2O3 content has significant effect on the properties of asphalt cement. The viscosity of the modified asphalt cement increased up to 90 and 108% respectively compared to the base asphalt cement. In addition, the results showed that both modifiers have great storage stability and compatibility at elevated temperature. The evaluation of the rheological properties of asphalt cements revealed that the stiffness of the modified samples improved with additional increase of the modifier concentration of up to 5%, which indicates better resistance to rutting parameter. The enhancement was up to 388.89% for Al2O3 and 74.07% for CaCO3. As a result, the usage of CaCO3 and Al2O3 nanoparticles can be considered as appropriate alternative materials to modify asphalt cement.

Vegetable oil‐mediated thermal isomerization of (all‐E)‐lycopene: Facile and efficient production of Z‐isomers

Thermal isomerization of (all‐E)‐lycopene to the corresponding Z‐isomers was investigated in edible vegetable oils; perilla, linseed, grape seed, soybean, corn, sesame, rapeseed, rice bran, safflower seed, olive, and sunflower seed oil. Purified (all‐E)‐lycopene from tomato oleoresin was converted to Z‐isomers in the range of 44.8–58.8% content, and the remaining ratio of total amount of lycopene isomers without decomposition were ranged from 38.8 to 79.6% after heating at 100°C for 1 h in the vegetable oils. Both values were exceedingly high in sesame oil: 58.8% of total Z‐isomers content and 78.3% of remaining lycopene. In particular, (5Z)‐lycopene, which has higher bioavailability and antioxidant capacity as well as greater storage stability among the Z‐isomers, was notably increased in that oil; approximately threefold higher than the average of the other vegetable oils.Practical applications: Lycopene offers many health benefits such as decreased risk of cancer and arteriosclerosis. The Z‐isomers of lycopene, occurring in processed tomato products, are more bioavailable than the all‐E‐isomer which is a major configuration form in raw tomatoes. This study has developed an efficient production method for Z‐isomers of lycopene by heating (all‐E)‐lycopene in edible vegetable oils, in which neither organic solvents nor food additives are used. It would be practically feasible to utilize this procedure for the food, drink, and dietary supplement manufacturing, as well as for daily cooking at home.Thermal isomerization of (all‐E)‐lycopene to Z‐isomers was investigated in edible vegetable oils. In sesame oil, (5Z)‐lycopene, which has higher bioavailability, antioxidant capacity, and greater storage stability among the Z‐isomers, was increased significantly.

Using Vinyl Acetate, N‐Hydroxymethyl Acrylamide, and Montmorillonite Intercalated by a Dioctadecyl Dimethyl Ammonium Bromide Surfactant to Prepare Exfoliated Nanocomposite through In Situ Polymerization

ABSTRACTIn this study, vinyl acetate, N‐hydroxymethyl acrylamide (NMA), and organic montmorillonite intercalated by a dioctadecyl dimethyl ammonium bromide surfactant (MMT‐DOAB) were used to prepare exfoliated nanocomposites through in situ polymerization. Wide‐angle X‐ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, power‐law function equation, Newtonian fluid flow equation, Cross–Williamson model viscous equation, Hooke's law, and Poisson's ratio equation revealed the structures, dispersion, rheology, and static tensile properties. The exfoliated nanocomposites were pseudoplastic non‐Newtonian fluids with good dispersion in water, great storage stability, and high static tensile strength at 6.89–8.15 MPa. The contents of NMA and MMT‐DOAB increased with the changes in synthesis precursors, as the calculated molecular weights did.

Impact of enzyme stabilizers on the characteristics of biomodules for bioluminescent biosensors

The biomodule of bioluminescent biosensor based on a coupled enzyme system NADH:FMN-oxidoreductase and luciferase, co-immobilized with substrates in dried starch or gelatin gels, has been developed. We studied the impact of several stabilizers—dithiothreitol (DTT), bovine serum albumin (BSA) and mercaptoethanol (ME) on the biomodule's activity, storage stability and sensitivity to toxic substances. The inclusion of stabilizers increases the activity of the biological module by more than 150%. To achieve the combination of high activity, prolonged storage time and acute sensitivity to toxic substances within maximum permissible concentration we used starch gel as a carrier adding 100μM DTT to the immobilized preparation. The gelatin-based biological module had greater storage stability than the starch-based one but demonstrated less sensitivity to toxic substances.

Exfoliated Nanocomposites of Polyvinyl Acetate-N-Hydroxymethyl Acrylamide and Intercalated Montmorillonite from an Octadecyl Trimethyl Ammonium Bromide Surfactant

In this study, we introduced N-hydroxymethyl acrylamide and an organic montmorillonite intercalated by an octadecyl trimethyl ammonium bromide surfactant together into the in situ polymerization of polyvinyl acetate to form exfoliated nanocomposites. Wide-angle X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, power-law function equation, Newtonian fluid flow equation, Cross-Williamson model viscous equation, Hooke's law, and Poisson's ratio equation revealed the structures, dispersion, rheology, and static tensile properties. The exfoliated nanocomposites were pseudo-plastic non-Newtonian fluids, presented a good dispersion in water, a great storage stability, and a high static tensile strength at 6.78–8.06 MPa.

Stability and Releasing Property of Anthocyanins Microcapsules from &lt;i&gt;Acanthopanax&lt;/i&gt;&lt;i&gt;. s&lt;/i&gt;&lt;i&gt;essiliflorus (Rupr. et Maxim.)&lt;/i&gt; Seem

Anthocyanins microcapsules from Acanthopanax.sessiliflorus (Rupr. et Maxim.) Seem were prepared by Spray-Drying, using maltodextrin and gum arabic as wall materials. The stability and releasing property of anthocyanins microcapsules were studied. Using the retention rate as evaluation index, the effects of temperature, light, pH and metal ions on the stability of microcapsules and anthocyanins during 30 days storage were assessed, and samples were taken every five days. Results show that the microcapsules have greater storage stability against temperature, light, pH and metal ions. Using the release rate as evaluation index, the effect of releasing of microcapsules was evaluated, and samples were taken every 30min. Results show that the microcapsules have certain slow-release effect.

Acetone powder from dormant seeds of Ricinus communis L

The influence of several factors on the hydrolytic activity of lipase, present in the acetone powder from dormant castor seeds (Ricinus communis) was evaluated. The enzyme showed a marked specificity for short-chain substrates. The best reaction conditions were an acid medium, Triton X-100 as the emulsifying agent and a temperature of 30 degrees C. The lipase activity of the acetone powder of different castor oil genotypes showed great variability and storage stability of up to 90%. The toxicology analysis of the acetone powder from genotype Nordestina BRS 149 showed a higher ricin (toxic component) content, a lower 2S albumin (allergenic compound) content, and similar allergenic potential compared with untreated seeds.

Thermal behavior of pure rice bran oil, sunflower oil and their model blends during deep fat frying

Shall be deleted offer some advantages like better nutritional quality, lower cost and greater storage stability than pure oils. Model blends prepared from pure rice bran oil (RBO) and sunflower oil (SFO) were examined for change in their physico-chemical parameters (acid value, iodine value, color value, peroxide value and fatty acids). Repeated deep fat frying processes were carried out using dried potato chips in pure rice bran oil, sunflower oil and their model blends, in order to study the thermal behavior of pure rice bran oil, sunflower oil and their model blends. Pure rice bran oil and sunflower oil showed good thermal stability during the repeated deep fat frying cycles. Although all the blended oils used in the study showed good thermal stability during repeated deep fat frying cycles, model blends consisting of 60%RBO + 40% SFO showed better suitability during repeated deep fat frying than the remaining blended oils.