Water soluble hydrophobic peptoids via a minor backbone modification

2018 ◽  
Vol 16 (9) ◽  
pp. 1480-1488 ◽  
Author(s):  
Chandra Mohan Darapaneni ◽  
Prathap Jeya Kaniraj ◽  
Galia Maayan
Keyword(s):  
Water Solubility ◽  
Water Soluble ◽  
Conformational Order ◽  
Backbone Modification ◽  
A Minor

The incorporation of piperazine or homopiperazine within hydrophobic peptoid scaffolds leads to their water solubility while increasing their overall conformational order in water.

BODIPY Fluorophores for Membrane Potential Imaging

2019 ◽  
Author(s):  
Jenna Franke ◽  
Benjamin Raliski ◽  
Steven Boggess ◽  
Divya Natesan ◽  
Evan Koretsky ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Water Solubility ◽  
Water Soluble ◽  
Voltage Sensitivity ◽  
Chemical Transformations ◽  
Direct Modification ◽  
Biological Compatibility ◽  
Meso Position ◽  
Ionizable Groups ◽  
Boron Center

Fluorophores based on the BODIPY scaffold are prized for their tunable excitation and emission profiles, mild syntheses, and biological compatibility. Improving the water-solubility of BODIPY dyes remains an outstanding challenge. The development of water-soluble BODIPY dyes usually involves direct modification of the BODIPY fluorophore core with ionizable groups or substitution at the boron center. While these strategies are effective for the generation of water-soluble fluorophores, they are challenging to implement when developing BODIPY-based indicators: direct modification of BODIPY core can disrupt the electronics of the dye, complicating the design of functional indicators; and substitution at the boron center often renders the resultant BODIPY incompatible with the chemical transformations required to generate fluorescent sensors. In this study, we show that BODIPYs bearing a sulfonated aromatic group at the meso position provide a general solution for water-soluble BODIPYs. We outline the route to a suite of 5 new sulfonated BODIPYs with 2,6-disubstitution patterns spanning a range of electron-donating and -withdrawing propensities. To highlight the utility of these new, sulfonated BODIPYs, we further functionalize them to access 13 new, BODIPY-based voltage-sensitive fluorophores. The most sensitive of these BODIPY VF dyes displays a 48% ΔF/F per 100 mV in mammalian cells. Two additional BODIPY VFs show good voltage sensitivity (≥24% ΔF/F) and excellent brightness in cells. These compounds can report on action potential dynamics in both mammalian neurons and human stem cell-derived cardiomyocytes. Accessing a range of substituents in the context of a water soluble BODIPY fluorophore provides opportunities to tune the electronic properties of water-soluble BODIPY dyes for functional indicators.

scholarly journals Synthesis, Characterization and Bactericidal Activity of a 4-Ammoniumbuthylstyrene-Based Random Copolymer

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1140
Author(s):  
Silvana Alfei ◽  
Gabriella Piatti ◽  
Debora Caviglia ◽  
Anna Maria Schito
Keyword(s):  
Antibacterial Activity ◽  
Bactericidal Activity ◽  
Antimicrobial Agents ◽  
Water Solubility ◽  
Physicochemical Characterization ◽  
Random Copolymer ◽  
Water Soluble ◽  
Cationic Polymers ◽  
Severe Infections

The growing resistance of bacteria to current chemotherapy is a global concern that urgently requires new and effective antimicrobial agents, aimed at curing untreatable infection, reducing unacceptable healthcare costs and human mortality. Cationic polymers, that mimic antimicrobial cationic peptides, represent promising broad-spectrum agents, being less susceptible to develop resistance than low molecular weight antibiotics. We, thus, designed, and herein report, the synthesis and physicochemical characterization of a water-soluble cationic copolymer (P5), obtained by copolymerizing the laboratory-made monomer 4-ammoniumbuthylstyrene hydrochloride with di-methyl-acrylamide as uncharged diluent. The antibacterial activity of P5 was assessed against several multi-drug-resistant clinical isolates of both Gram-positive and Gram-negative species. Except for strains characterized by modifications of the membrane charge, most of the tested isolates were sensible to the new molecule. P5 showed remarkable antibacterial activity against several isolates of genera Enterococcus, Staphylococcus, Pseudomonas, Klebsiella, and against Escherichia coli, Acinetobacter baumannii and Stenotrophomonas maltophilia, displaying a minimum MIC value of 3.15 µM. In time-killing and turbidimetric studies, P5 displayed a rapid non-lytic bactericidal activity. Due to its water-solubility and wide bactericidal spectrum, P5 could represent a promising novel agent capable of overcoming severe infections sustained by bacteria resistant the presently available antibiotics.

scholarly journals Effect of DMPA and Molecular Weight of Polyethylene Glycol on Water-Soluble Polyurethane

Polymers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1915 ◽  
Author(s):  
Eyob Wondu ◽  
Hyun Woo Oh ◽  
Jooheon Kim
Keyword(s):  
Molecular Weight ◽  
Contact Angle ◽  
Polyethylene Glycol ◽  
Photoelectron Spectroscopy ◽  
Water Solubility ◽  
Soft Segment ◽  
Water Soluble ◽  
Size Exclusion ◽  
Resonance Spectroscopy ◽  
Scanning Calorimetry

In this study water-soluble polyurethane (WSPU) was synthesized from isophorone diisocyanate (IPDI), and polyethylene glycol (PEG), 2-bis(hydroxymethyl) propionic acid or dimethylolpropionic acid (DMPA), butane-1,4-diol (BD), and triethylamine (TEA) using an acetone process. The water solubility was investigated by solubilizing the polymer in water and measuring the contact angle and the results indicated that water solubility and contact angle tendency were increased as the molecular weight of the soft segment decreased, the amount of emulsifier was increased, and soft segment to hard segment ratio was lower. The contact angle of samples without emulsifier was greater than 87°, while that of with emulsifier was less than 67°, indicating a shift from highly hydrophobic to hydrophilic. The WSPU was also analyzed using Fourier transform infrared spectroscopy (FT-IR) to identify the absorption of functional groups and further checked by X-ray photoelectron spectroscopy (XPS). The molecular weight of WSPU was measured using size-exclusion chromatography (SEC). The structure of the WSPU was confirmed by nuclear magnetic resonance spectroscopy (NMR). The thermal properties of WSPU were analyzed using thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC).

scholarly journals Enhanced Water Solubility and Oral Bioavailability of Paclitaxel Crystal Powders through an Innovative Antisolvent Precipitation Process: Antisolvent Crystallization Using Ionic Liquids as Solvent

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1008 ◽  
Author(s):  
Qilei Yang ◽  
Chang Zu ◽  
Wengang Li ◽  
Weiwei Wu ◽  
Yunlong Ge ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
High Performance ◽  
Water Solubility ◽  
Water Soluble ◽  
Precipitation Process ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Antisolvent Precipitation ◽  
Antisolvent Crystallization ◽  
Artificial Gastric Juice

Paclitaxel (PTX) is a poor water-soluble antineoplastic drug with significant antitumor activity. However, its low bioavailability is a major obstacle for its biomedical applications. Thus, this experiment is designed to prepare PTX crystal powders through an antisolvent precipitation process using 1-hexyl-3-methylimidazolium bromide (HMImBr) as solvent and water as an antisolvent. The factors influencing saturation solubility of PTX crystal powders in water in water were optimized using a single-factor design. The optimum conditions for the antisolvent precipitation process were as follows: 50 mg/mL concentration of the PTX solution, 25 °C temperature, and 1:7 solvent-to-antisolvent ratio. The PTX crystal powders were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, high-performance liquid chromatography–mass spectrometry, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Raman spectroscopy, solid-state nuclear magnetic resonance, and dissolution and oral bioavailability studies. Results showed that the chemical structure of PTX crystal powders were unchanged; however, precipitation of the crystalline structure changed. The dissolution test showed that the dissolution rate and solubility of PTX crystal powders were nearly 3.21-folds higher compared to raw PTX in water, and 1.27 times higher in artificial gastric juice. Meanwhile, the bioavailability of PTX crystal increased 10.88 times than raw PTX. These results suggested that PTX crystal powders might have potential value to become a new oral PTX formulation with high bioavailability.

scholarly journals Dietary Fiber, Atherosclerosis, and Cardiovascular Disease

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1155 ◽  
Author(s):  
Ghada A. Soliman
Keyword(s):  
Cardiovascular Disease ◽  
Dietary Fiber ◽  
Water Solubility ◽  
Disease Risk ◽  
Current Knowledge ◽  
Digestive Enzyme ◽  
Water Soluble ◽  
Blood Cholesterol ◽  
Fiber Intake ◽  
Intestinal Transit Time

Observational studies have shown that dietary fiber intake is associated with decreased risk of cardiovascular disease. Dietary fiber is a non-digestible form of carbohydrates, due to the lack of the digestive enzyme in humans required to digest fiber. Dietary fibers and lignin are intrinsic to plants and are classified according to their water solubility properties as either soluble or insoluble fibers. Water-soluble fibers include pectin, gums, mucilage, fructans, and some resistant starches. They are present in some fruits, vegetables, oats, and barley. Soluble fibers have been shown to lower blood cholesterol by several mechanisms. On the other hand, water-insoluble fibers mainly include lignin, cellulose, and hemicellulose; whole-grain foods, bran, nuts, and seeds are rich in these fibers. Water-insoluble fibers have rapid gastric emptying, and as such may decrease the intestinal transit time and increase fecal bulk, thus promoting digestive regularity. In addition to dietary fiber, isolated and extracted fibers are known as functional fiber and have been shown to induce beneficial health effects when added to food during processing. The recommended daily allowances (RDAs) for total fiber intake for men and women aged 19–50 are 38 gram/day and 25 gram/day, respectively. It is worth noting that the RDA recommendations are for healthy people and do not apply to individuals with some chronic diseases. Studies have shown that most Americans do not consume the recommended intake of fiber. This review will summarize the current knowledge regarding dietary fiber, sources of food containing fiber, atherosclerosis, and heart disease risk reduction.

The Emerging Role of Nanosuspensions for Drug Delivery and Stability

2021 ◽  
Vol 12 ◽  
Author(s):  
Hitesh Kumar Dewangan
Keyword(s):  
Water Solubility ◽  
Size Range ◽  
Aqueous Solubility ◽  
Active Surface ◽  
Water Soluble ◽  
Active Surface Area ◽  
Specific Interest ◽  
Advanced Therapies ◽  
Processing Techniques

: Poor solubility of some medicinal compounds is a serious challenge that can be addressed by using a nano-suspension for improved delivery. The nanoparticles enhance the bioavailability along with the aqueous solubility of the drug, which is accomplished by increasing the active surface area of the drug. The gained attention of the nanosuspension is due to its stabilization facility, which is achieved by polymers, such as polyethylene glycol (PEG), having a particular size range of 10 - 100 nm. Hence, these nanoparticles have the capacity of binding to the targeted with very low damage to the healthy tissues. These are prepared by various methods, such as milling, high-pressure homogenization, and emulsification, along with melt emulsification. Moreover, surface modification and solidification have been used to add specific properties to the advanced therapies as post-processing techniques. For many decades, it has been known that water solubility hampers the bioavailability and not all drugs are water-soluble. In order to combat this obstacle, nanotechnology has been found to be of specific interest. For elevating the bioavailability by increasing the dissolution rate, the methodology of reduction of the associated drug particles into their subsequent submicron range is incorporated. For oral and non-oral administration, these nanosuspension formulations are used for the delivery of drugs.

Formulation and Evaluation of Benidipine Nanosuspension

2021 ◽  
pp. 4111-4116
Author(s):  
Sejal Patel ◽  
Anita P. Patel
Keyword(s):  
Particle Size ◽  
Water Solubility ◽  
Polymer Concentration ◽  
Oral Route ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
23 Factorial Design ◽  
Selection Of

In the interest of administration of dosage form oral route is most desirable and preferred method. After oral administration to get maximum therapeutic effect, major challenge is their water solubility. Water insoluble drug indicate insufficient bioavailability as well dissolution resulting in fluctuating plasma level. Benidipine (BND) is poorly water soluble antihypertensive drug has lower bioavailability. To improve bioavailability of Benidipine HCL, BND nanosuspension was formulated using media milling technique. HPMC E5 was used to stabilize nanosuspension. The effect of different important process parameters e.g. selection of polymer concentration X1(1.25 mg), stirring time X2 (800 rpm), selection of zirconium beads size X3 (0.4mm) were investigated by 23 factorial design to accomplish desired particle size and saturation solubility. The optimized batch had 408 nm particle size Y1, and showed in-vitro dissolution Y2 95±0.26 % in 30 mins and Zeta potential was -19.6. Differential scanning calorimetry (DSC) and FT-IR analysis was done to confirm there was no interaction between drug and polymer.

scholarly journals Tests of the sorption and olfactory “fovea” hypotheses in the mouse

2017 ◽  
Vol 118 (5) ◽  
pp. 2770-2788 ◽  
Author(s):  
David M. Coppola ◽  
Brittaney E. Ritchie ◽  
Brent A. Craven
Keyword(s):  
Olfactory Epithelium ◽  
Water Solubility ◽  
Fluid Dynamic ◽  
Water Soluble ◽  
Quiet Breathing ◽  
Cfd Simulations ◽  
Dynamic Simulations ◽  
Consistent Finding ◽  
Sensory Epithelia ◽  
Tactile Stimuli

The spatial distribution of receptors within sensory epithelia (e.g., retina and skin) is often markedly nonuniform to gain efficiency in information capture and neural processing. By contrast, odors, unlike visual and tactile stimuli, have no obvious spatial dimension. What need then could there be for either nearest-neighbor relationships or nonuniform distributions of receptor cells in the olfactory epithelium (OE)? Adrian (Adrian ED. J Physiol 100: 459–473, 1942; Adrian ED. Br Med Bull 6: 330–332, 1950) provided the only widely debated answer to this question when he posited that the physical properties of odors, such as volatility and water solubility, determine a spatial pattern of stimulation across the OE that could aid odor discrimination. Unfortunately, despite its longevity, few critical tests of the “sorption hypothesis” exist. Here we test the predictions of this hypothesis by mapping mouse OE responses using the electroolfactogram (EOG) and comparing these response “maps” to computational fluid dynamics (CFD) simulations of airflow and odorant sorption patterns in the nasal cavity. CFD simulations were performed for airflow rates corresponding to quiet breathing and sniffing. Consistent with predictions of the sorption hypothesis, water-soluble odorants tended to evoke larger EOG responses in the central portion of the OE than the peripheral portion. However, sorption simulation patterns along individual nasal turbinates for particular odorants did not correlate with their EOG response gradients. Indeed, the most consistent finding was a rostral-greater to caudal-lesser response gradient for all the odorants tested that is unexplained by sorption patterns. The viability of the sorption and related olfactory “fovea” hypotheses are discussed in light of these findings. NEW & NOTEWORTHY Two classical ideas concerning olfaction’s receptor-surface two-dimensional organization—the sorption and olfactory fovea hypotheses—were found wanting in this study that afforded unprecedented comparisons between electrophysiological recordings in the mouse olfactory epithelium and computational fluid dynamic simulations of nasal airflow. Alternatively, it is proposed that the olfactory receptor layouts in macrosmatic mammals may be an evolutionary contingent state devoid of the functional significance found in other sensory epithelia like the cochlea and retina.

scholarly journals Synthesis of Water-Soluble 7-O-Carboxymethyl-Genistein

2017 ◽  
Vol 41 (3) ◽  
pp. 183-185
Author(s):  
Zhiling Cao ◽  
Qiao Wu ◽  
Jing Cheng ◽  
Dandan Zhu ◽  
Wengqi Teng ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Sodium Salt ◽  
Water Solubility ◽  
Clinical Chemistry ◽  
Water Soluble ◽  
Aqueous Acetic Acid ◽  
Carboxylate Group ◽  
Target Compound ◽  
Catalysed Reaction

A three-step synthesis from genistein of the water-soluble sodium salt of 7-O-carboxymethyl-genistein is described. Base-catalysed reaction of genistein with t-butyl bromoacetate gave 7-O-(carbo-t-butoxy)methyl-genistein, which was hydrolysed by aqueous acetic acid to 7-O-carboxymethyl-genistein and neutralised (NaHCO3) to give the target compound. The carboxylate group enhanced the water-solubility of genistein more than a thousand-fold and the new derivate will be useful as a candidate compound in pharmacological and clinical chemistry studies of isoflavones.

scholarly journals Improvement of Imiquimod Solubilization and Skin Retention via TPGS Micelles: Exploiting the Co-Solubilizing Effect of Oleic Acid

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1476
Author(s):  
Martina Ghezzi ◽  
Silvia Pescina ◽  
Andrea Delledonne ◽  
Ilaria Ferraboschi ◽  
Cristina Sissa ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Water Solubility ◽  
Skin Penetration ◽  
Water Soluble ◽  
Drug Solubility ◽  
Two Photon Microscopy ◽  
Skin Delivery ◽  
Polyethylene Glycol 1000 ◽  
The One ◽  
Skin Retention

Imiquimod (IMQ) is an immunostimulant drug approved for the topical treatment of actinic keratosis, external genital-perianal warts as well as superficial basal cell carcinoma that is used off-label for the treatment of different forms of skin cancers, including some malignant melanocytic proliferations such as lentigo maligna, atypical nevi and other in situ melanoma-related diseases. Imiquimod skin delivery has proven to be a real challenge due to its very low water-solubility and reduced skin penetration capacity. The aim of the work was to improve the drug solubility and skin retention using micelles of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of vitamin E, co-encapsulating various lipophilic compounds with the potential ability to improve imiquimod affinity for the micellar core, and thus its loading into the nanocarrier. The formulations were characterized in terms of particle size, zeta potential and stability over time and micelles performance on the skin was evaluated through the quantification of imiquimod retention in the skin layers and the visualization of a micelle-loaded fluorescent dye by two-photon microscopy. The results showed that imiquimod solubility strictly depends on the nature and concentration of the co-encapsulated compounds. The micellar formulation based on TPGS and oleic acid was identified as the most interesting in terms of both drug solubility (which was increased from few µg/mL to 1154.01 ± 112.78 µg/mL) and micellar stability (which was evaluated up to 6 months from micelles preparation). The delivery efficiency after the application of this formulation alone or incorporated in hydrogels showed to be 42- and 25-folds higher than the one of the commercial creams.

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