Formation of Molecular Complexes by Some Water‐Soluble Amides II. Effect of Decreasing Water Solubility on Degree of Complex Formation**School of Pharmacy, University of Wisconsin, Madison

The article discusses the results of a study of the water solubility of natural sesquiterpene lactone arglabin, in particular, its ability to complex formation with complexing agents polyvinylpyrrolidone, the disodium salt of glycyrrhizic acid, magnesium carbonate. Mechanocomposites with polyvinylpyrrolidone and disodium salt of glycyrrhizic acid, which have increased water solubility, were obtained by the method of mechanochemical treatment of arglabin native. At the same time, the best result of dissolution in water is achieved by a two-hour treatment with polyvinylpyrrolidone and with disodium salt of glycyrrhizic acid. The water solubility of complex compounds of arglabin with polyvinylpyrrolidone increases by 4.61 times, and with disodium salt of glycyrrhizic acid by 4.42 times.

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Orthogonal self-assembly of an organoplatinum(II) metallacycle and cucurbit[8]uril that delivers curcumin to cancer cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1803800115 ◽

2018 ◽

Vol 115 (32) ◽

pp. 8087-8092 ◽

Cited By ~ 30

Author(s):

Sougata Datta ◽

Santosh K. Misra ◽

Manik Lal Saha ◽

Nabajit Lahiri ◽

Janis Louie ◽

...

Keyword(s):

Complex Formation ◽

Cancer Cells ◽

Self Assembly ◽

Water Solubility ◽

Therapeutic Potential ◽

Water Soluble ◽

Spectroscopic Techniques ◽

Guest Complex ◽

Host Guest Complex ◽

Stat3 Phosphorylation

Curcumin (Cur) is a naturally occurring anticancer drug isolated from the Curcuma longa plant. It is known to exhibit anticancer properties via inhibiting the STAT3 phosphorylation process. However, its poor water solubility and low bioavailability impede its clinical application. Herein, we used organoplatinum(II) ← pyridyl coordination-driven self-assembly and a cucurbit[8]uril (CB[8])-mediated heteroternary host–guest complex formation in concert to produce an effective delivery system that transports Cur into the cancer cells. Specifically, a hexagon 1, containing hydrophilic methyl viologen (MV) units and 3,4,5-Tris[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]benzoyl groups alternatively at the vertices, has been synthesized and characterized by several spectroscopic techniques. The MV units of 1 underwent noncovalent complexation with CB[8] to yield a host–guest complex 4. Cur can be encapsulated in 4, via a 1:1:1 heteroternary complex formation, resulting in a water-soluble host–guest complex 5. The host–guest complex 5 exhibited ca. 100-fold improved IC50 values relative to free Cur against human melanoma (C32), melanoma of rodents (B16F10), and hormone-responsive (MCF-7) and triple-negative (MDA-MB231) breast cancer cells. Moreover, strong synergisms of Cur with 1 and 4 with combinatorial indexes of <1 across all of the cell lines were observed. An induced apoptosis with fragmented DNA pattern and inhibited expression of phosphor-STAT3 supported the improved therapeutic potential of Cur in heteroternary complex 5.

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BODIPY Fluorophores for Membrane Potential Imaging

10.26434/chemrxiv.8219057.v1 ◽

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.

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

Polymers ◽

10.3390/polym13071140 ◽

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.

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

Polymers ◽

10.3390/polym11121915 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1915 ◽

Cited By ~ 2

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).

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

Pharmaceutics ◽

10.3390/pharmaceutics12111008 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1008 ◽

Cited By ~ 1

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.

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Dietary Fiber, Atherosclerosis, and Cardiovascular Disease

Nutrients ◽

10.3390/nu11051155 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1155 ◽

Cited By ~ 30

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.

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Water-Soluble Vitamin D in Human Milk: A Myth

PEDIATRICS ◽

10.1542/peds.70.3.499a ◽

1982 ◽

Vol 70 (3) ◽

pp. 499-499

Author(s):

Joseph A. Little

Keyword(s):

Vitamin D ◽

Human Milk ◽

Clinical Observation ◽

Water Soluble ◽

University Of Wisconsin ◽

Water Soluble Vitamin ◽

The University ◽

Breast Fed

I was happy to read the report from Greer et al.1 This biochemically confirms the clinical observation that the majority of children who develop clinical rickets are breast-fed. During the ten years, 1970-1979, I have seen six cases of clinical rickets. All of these infants were breast-fed.2 The only exception has been the rickets of prematurity. I should like to commend, again, the report from the Department of Pediatrics and Biochemistry of the University of Wisconsin.

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The Emerging Role of Nanosuspensions for Drug Delivery and Stability

Current Nanomedicine ◽

10.2174/2468187312666211222123307 ◽

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.

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Formulation and Evaluation of Benidipine Nanosuspension

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00712 ◽

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.

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