Hydrophobic Derivatives Research Articles

Synergistic enhancement of chlorophenols removal using eco-friendly alginate@montmorillonite hybrid bio-capsules: insights from encapsulation and kinetic release studies

This study investigates the synergistic effects of alginate@montmorillonite (Alg@Mt) hybrid microcapsules for enhancing water purification, focusing on improving the encapsulation of hydrophobic contaminants. Alg@Mt microcapsules were prepared through ionotropic gelation. Characterisation was performed using SEM-EDX, FTIR, XRD, and TGA. Encapsulation efficiency (EE), loading capacity (LC), and release behaviour were also examined. Alg@Mt microcapsules effectively removed phenol and its chlorinated derivatives from water. Incorporating Na-Mt improved structural and thermal properties, EE, and LC. Increasing the clay content to 60% (w/w) raised the EE of phenol and its more hydrophobic derivative, 2,4,6-trichlorophenol, from 39.74 ± 3.1% (w/w) and 63.91 ± 2% (w/w) to 60.56 ± 1.6% (w/w) and 82.28 ± 2.3% (w/w), respectively, with more controlled release rates, following Fickian diffusion mechanism. EE increased with phenolic substances hydrophobicity, while LC and release rates were inversely related. This approach is promising for removing hydrophobic contaminants from water.

Superelastic Polymer Aerogel with Superamphiphilicity.

Elastic aerogels have become a research hot spot in both academia and industry recently. The reported elastic aerogels are all made of hard materials by controlling their shapes. Herein we report an elastic aerogel made of a polymer elastomer with entropy elasticity. In the aerogel, cross-linked carboxyl nitrile rubber nanoparticles with hydrophilicity are dispersed in hydrophobic derivative of styrene-maleic anhydride alternating copolymer, forming a very special micro-nano surface structure with hydrophilic protrusions and hydrophobic depressions on the aerogel wall; therefore, the aerogel is not only superelastic but also superamphiphilic. A leak-free phase-change composite was prepared using the aerogel and paraffin, which can maintain at phase change temperature of paraffin for a longer time than the traditional one. The aerogel is also extremely suitable for desalination evaporators in solar-driven interfacial evaporation technology due to its superamphiphilicity, superelasticity, and ability to absorb sunlight. Exceptional evaporation rate of 2.78 kg·m-2·h-1 and evaporation efficiency of 170% could be reached even without using expensive light-absorbing materials. The evaporation rate exceeds that of most evaporators with expensive light-absorbing materials, and the evaporation efficiency exceeds the theoretical limit of conventional 2D solar evaporators. Both the phase-change composite and the evaporator can be easily recovered because the novel superelastic aerogel reported in this work is also recyclable.

Molecular mechanism of protein aggregation inhibition with sulfobetaine polymers and their hydrophobic derivatives

Molecular mechanism of protein aggregation inhibition with sulfobetaine polymers and their hydrophobic derivatives

Antitumor effects of vitamin B12 in vitro, in vivo, in silico

Objective: to investigate the antitumor effects of various forms of vitamin B12 in combination with various synergistic vitamins and evaluate the prospects for clinical applications.Material and methods. Cell lines BT-474 (breast ductal carcinoma) and A549 (lung carcinoma) were used as an in vitro cell model, and transplantable epidermoid Lewis lung carcinoma (LLC) was used as an in vivo animal tumor model. Animal studies of LLC were carried out on 25 male F1 hybrid mice (age 2.5–3 months, body weight 23–26 g). In silico research was conducted as a systematic computer analysis of 9,326 scientific sources.Results. In vitro studies on cultures of two human tumor cell lines (BT-474 and A549) confirmed the cytotoxic effect of vitamin B12 (aquacobalamin). It has been shown that vitamin B12 has weak cytotoxic properties in the concentration range of 3.125–200 μg/L (IC50>200 nM), and its hydrophobic derivative (heptamethyl cyanoquacobyric acid ester) significantly reduces the survival of tumor lines. BT-474 and A549 cells at high concentrations (100–200 µg/l, IC50~100 nM). Experimental animals with an in vivo LLС model easily tolerated a drug based on vitamin B12. Exposure to the drug up to the 21st day of LLС development was accompanied by an increasing tendency to inhibit tumor growth by 10–20% (р=0.059). The results of a systematic in silico review of the literature show that clinical data confirmed the significant antitumor effect of vitamin B12.Conclusion. The cellular model indicated the antitumor properties of vitamin B12 and its hydrophobic derivative. With subchronic intragastric administration of B12 to tumor-bearing animals, a steady tendency to inhibit the LLС growth was observed. Analysis of clinical data confirmed the feasibility of the antitumor use of vitamin B12 individually and in combination with synergistic vitamins.

Exploring the Use of Hydroxytyrosol and Some of Its Esters in Food-Grade Nanoemulsions: Establishing Connection between Structure and Efficiency.

The efficiency of HT and that of some of its hydrophobic derivatives and their distribution and effective concentrations were investigated in fish oil-in-water nanoemulsions. For this purpose, we carried out two sets of independent, but complementary, kinetic experiments in the same intact fish nanoemulsions. In one of them, we monitored the progress of lipid oxidation in intact nanoemulsions by monitoring the formation of conjugated dienes with time. In the second set of experiments, we determined the distributions and effective concentrations of HT and its derivatives in the same intact nanoemulsions as those employed in the oxidation experiments. Results show that the antioxidant efficiency is consistent with the "cut-off" effect-the efficiency of HT derivatives increases upon increasing their hydrophobicity up to the octyl derivative after which a further increase in the hydrophobicity decreases their efficiency. Results indicate that the effective interfacial concentration is the main factor controlling the efficiency of the antioxidants and that such efficiency strongly depends on the surfactant concentration and on the oil-to-water (o/w) ratio employed to prepare the nanoemulsions.

Complexes of an Anionic Surfactant with Chitosan and Its Hydrophobic Derivatives As Disinfectants against SARS-CoV-2

Complexes of an Anionic Surfactant with Chitosan and Its Hydrophobic Derivatives As Disinfectants against SARS-CoV-2

Complexes of an Anionic Surfactant with Chitosan and Its Hydrophobic Derivatives As Disinfectants against SARS-CoV-2

This work is aimed at the preparation of complexes of chitosan and hydrophobically modified (HM) chitosan with an anionic surfactant sodium dodecylbenzene sulfonate (SDBS), and at the study of the virucidal activity of the complexes and their components against SARS-CoV-2. It is shown that the introduction of a sufficient amount (4 mol%) of hydrophobic n-dodecyl side groups provides the activity of HM chitosan against SARS-CoV-2 at moderate concentrations, at which unmodified chitosan and chitosan containing a lower amount of hydrophobic groups do not show any activity. Complexes of HM chitosan with SDBS are prepared, which is proven by fluorescence spectroscopy and isothermal titration calorimetry. It is discovered that HM chitosan/SDBS complex is more active than the polymer without surfactant, and an increase of the amount of hydrophobic groups enhances the activity

Optimization of nanofiber‐caproate/laurate esters synthesis, their characterization, and usage as emulsifier in o/w emulsion

AbstractThe aim of this study is to optimize the esterification of nanofibers with caproyl/lauroyl chlorides at different substitution degrees' (DS) and to investigate the usage of nanofiber derivatives in model emulsions. First, cellulosic material was obtained and milled into nanofibers using a micro‐fluidizer. Then, these nanofibers were esterified with caproyl/lauroyl chlorides in a solvent of DMAc/LiCl with DMAP as an acid scavenger. The esterification of nanofibers with caproyl/lauroyl chlorides was optimized for fatty acid chloride mole and reaction time. Esterification reactions were carried out at 80°C with various molar ratios of acyl chlorides (3–15 moles) versus anhydroglucose unit of nanofibers and for various time durations (30–360 min). The hydrophobic derivatives with DS in the range of 0.34–2.77 were successfully obtained. Using the data obtained as a result of the optimization, nanofiber‐fatty acid esters with different DS (0.50–2.75) were produced and characterized. Analyzes showed that the esterification process was successful and as the degree of esterification increased, the crystallinity index and thermal stability of the derivatives decreased. Then, the nanofiber‐caproate/laurate esters with different DS were used as emulsifier (0.5 wt%) in an oil‐in‐water model emulsion containing 25 wt% oil and the emulsions were analyzed. The nanofiber caproate/laurate esters with a DS of 0.50–1.25 were suitable for o/w emulsions, while samples with a DS of 2.00 and above were not found suitable. Emulsions prepared by using nanofiber derivatives with 1.25 DS had higher G′ and G″ and viscosity values and lower droplet sizes than those of other group.

Evaluation of Non-Cross Linked Xeno-Free Hyaluronic Acid Solutions as Visco Elastic Biomaterials.

Hyaluronic acid (HA) is a naturally occurring biodegradable, high molecular weight, non-sulfated glycosaminoglycan (GAG) polymer known for its excellent biocompatibility. HA-based products are widely used as viscosupplements, dermal fillers, and ophthalmic lubricants in clinical settings. Although animal and bacterial-derived HA are commonly reported, plant-sourced HA is not frequently reported. In this study, we have evaluated various viscoelastic properties of one such plant-based HA solution and propose them as an alternative to existing animal/bacteria-sourced HA. The viscoelastic properties of plant-sourced HA solution of various concentrations (0.1%, 0.5%, 1%, and 2% in PBS) were studied using a rheometer at 37°C. Flow curves, amplitude sweep studies, and frequency sweep studies were performed and compared for all HA solutions. The HA solutions displayed shear-thinning behavior, which is an important characteristic of an injectable biomaterial. The 0.1 and 0.5% HA were found to have viscoelastic properties appropriate for eye lubricants, while 1 and 2% HA solutions showed properties suitable for soft tissue fillers. Frequency sweep studies indicated that all the samples are typically viscoelastic liquids with a loss modulus (G″) higher than the storage modulus (G'). This indicated that the samples needed further processing like crosslinking of HA or using higher molecular weight HA to be suitable as viscosupplements. However, the frequency sweep studies also indicated that these solutions can be used as soft tissue fillers of any type based on the G' and tan δ values. The plant-sourced HA solutions are found to exhibit good shear-thinning properties with viscoelastic properties suitable for eye lubricants and soft tissue fillers. However, to be used as viscosupplements, the viscoelastic properties of HA solutions have to be further modified through non-toxic crosslinking strategies, and hydrophobic derivatives as well as by using high molecular weight HAs.

Polyampholytes and Their Hydrophobic Derivatives as Excipients for Suppressing Protein Aggregation.

Protein aggregation, which occurs under various physiological conditions, can affect cell function and is a major issue in the field of protein therapeutics. In this study, we developed a polyampholyte composed of ε-poly-l-lysine and succinic anhydride and evaluated its protein protection efficacy. This polymer was able to protect different proteins from thermal stress and its performance significantly exceeded that of previously reported zwitterionic polymers. In addition, we synthesized derivatives with varying degrees of hydrophobicity, which exhibited remarkably enhanced efficiency; thus, the polymer concentration required for protein protection was very low. By facilitating the retention of protein enzymatic activity and stabilizing the higher-order structure, these polymers enabled the protein to maintain its native state, even after being subjected to extreme thermal stress. Thus, such polyampholytes are extremely effective in protecting proteins from extreme stress and may find applications in protein biopharmaceuticals and drug delivery systems.

Determination of Phosphoethanolamine in Urine with HPLC-ICPMS/MS Using 1,2-Hexanediol as a Chromatographic Eluent.

The importance of element-selective detection with inductively coupled plasma mass spectrometry (ICPMS) has been significantly increased in recent years following the introduction of tandem ICPMS (ICPMS/MS), which unlocked access to nonmetal speciation analysis. However, nonmetals are ubiquitous, and the feasibility of nonmetal speciation analysis in matrices with complex metabolomes is yet to be demonstrated. Herein, we report the first phosphorous speciation study by HPLC-ICPMS/MS in a human sample, namely, urine, involving the determination of the natural metabolite and biomarker phosphoethanolamine. A simple one-step derivatization procedure was employed to enable the separation of the target compound from the hydrophilic phosphorous metabolome in urine. The challenge of eluting the hydrophobic derivative under ICPMS-compatible chromatographic conditions was addressed by employing hexanediol, a novel chromatographic eluent recently described in our previous work but has not yet been exploited in a real-world application. The developed method features fast chromatographic separation (<5 min), no need for an isotopically labeled internal standard, and an instrumental LOD of 0.5 μg P L-1. The method was evaluated for recovery (90-110%), repeatability (RSD ±5%), and linearity (r2 = 0.9998). The method accuracy was thoroughly examined by comparing with an independently developed method based on HPLC-ESIMS/MS without derivatization, where agreement was found within ±5-20%. An application is presented to gain first insight into the variability in the human excretion of phosphoethanolamine, which is key for the interpretation of its levels as a biomarker, by repeated urine collection from a group of volunteers over 4 weeks.

Highly Efficient Synthesis of Chlorogenic Acid Oleyl Alcohol Ester under Non-Catalytic and Solvent-Free Conditions.

As a natural polyphenolic compound, chlorogenic acid (CGA) has attracted increasing attention for its various biological activities, such as antioxidant, liver protection, intestinal barrier protection, and effective treatment of obesity and type II diabetes. However, the poor solubility of CGA in hydrophobic media limits its application in the food, drug and cosmetic industries. In order to obtain new hydrophobic derivatives, a highly efficient synthesis approach of CGA oleyl alcohol ester (CGOA) under non-catalytic and solvent-free conditions was developed in this study. The influences of reaction temperature, reaction time, substrate molar ratio, and stirring rate on the CGA conversion were investigated. The results showed that the optimal conditions were as follows: reaction temperature 200 °C, reaction time 3 h, molar ratio of CGA to oleyl alcohol 1:20, and stirring rate 200 rpm. Under these conditions, the CGA conversion could reach 93.59%. Then, the obtained crude product was purified by solvent extraction and column chromatography, and the purify of CGOA was improved to 98.72%. Finally, the structure of CGOA was identified by FT-IR, HPLC-MS and NMR. This study provides a simple and efficient strategy for the preparation of CGOA with the avoidance of catalysts and solvents.

Membrane interaction and selectivity of novel alternating cationic lipid-nanodisc assembling polymers.

Synthetic polymer nanodiscs are self-assembled structures formed from amphipathic copolymers encapsulating membrane proteins and surrounding phospholipids into water soluble discs. These nanostructures have served as an analytical tool for the detergent free solubilisation and structural study of membrane proteins (MPs) in their native lipid environment. We established the polymer-lipid nanodisc forming ability of a novel class of amphipathic copolymer comprised of an alternating sequence of N-alkyl functionalised maleimide (AlkylM) of systematically varied hydrocarbon chain length, and cationic N-methyl-4-vinyl pyridinium iodide (MVP). Using a combination of physicochemical techniques, the solubilisation efficiency, size, structure and shape of DMPC lipid containing poly(MVP-co-AlkylM) nanodiscs were determined. Lipid solubilisation increased with AlkylM hydrocarbon chain length from methyl (MM), ethyl (EtM), n-propyl (PM), iso-butyl (IBM) through to n-butyl (BM) maleimide bearing polymers. More hydrophobic derivatives formed smaller sized nanodiscs and lipid ordering within poly(MVP-co-AlkylM) nanodiscs was affected by nanodisc size. In dye-release assays, shorter N-alkyl substituted polymers, particularly poly(MVP-co-EtM), exhibited low activities against eukaryotic mimetic POPC membrane and increased their liposome disruption as POPC : POPG membrane mixtures increased in their anionic POPG component, resembling the charge profile of bacterial membranes. These trends in membrane selectivity were transferred towards native cell systems in which gram-positive Staphylococcus aureus and gram-negative Acenobacter baumannii bacterial strains were relatively susceptible to disruption by hydrophobic n-butyl- and n-propyl-poly(MVP-co-AlkylM) derivatives compared to human red blood cells (HRBCs), with a more pronounced selectivity resulting from poly(MVP-co-PM). Such selective membrane interaction by less hydrophobic polymers provides a framework for polymer design towards applications including selective membrane component solubilisation, biosensing and antimicrobial development.

ХЕЛАТУВАННЯ ДВОВАЛЕНТНИХ КАТІОНІВ ТА АНТИРАКОВА АКТИВНІСТЬПОХІДНИХ 8-ГІДРОКСИСТИРИЛХІНОЛІНІВ IN VITRO

Background. The search for new methods of cancer treatment and diagnosis are important. The disadvantages of chemotherapy drugs are the rapid acquisition of resistance and high toxicity. 8-hydroxyquinoline derivatives have a wide spectrum of biological activity and have the necessary properties for fluorescent cancer diagnosis. The aim of the study was to determine the chelation of calcium, magnesium and zinc cations by hydrophobic derivatives of 8-hydroxystyrylquinolines (8HQ) 2-(4-chlorostyryl)quinolin-8-ol (STQ-Cl) and 2-(4-nitrostyryl)quinolin-8-ol (STQ-NO2) in physiological solution, the stability of the complexes and the cytotoxicity of the compounds to prostate and breast cancer cell lines in vitro. Methods. 8HQ derivatives STQ-Cl and STQ-NO2 were used. Solutions of Ca2+, Mg2+, Zn2+ cations were prepared by the method of two-fold dilutions in 0.5-0.0078125 mM concentration range based on 0.9 % NaCl. Both individual solutions of each cation and a mixture in an equivalent molar ratio were used. The concentration of 8HQ derivatives were 0.05 mM. Optical absorption was registered in 200-700 nm wavelength range. Cytotoxicity was investigated on breast (MDA-MB-231) and prostate (DU-145) cancer cell lines. STQ-Cl and STQ-NO2 derivatives in DMSO were added to the incubation solution by four-fold dilutions (0.125–0.00003 mM). For luminescence studies, MDA-MB-231 and DU-145 cells were grown on coverslips. The final concentration of 8HQ derivatives were 5 mM. Cells were kept for 5, 10, 20 and 30 min. Luminescence was recorded under the same conditions for all samples, with an exposure time of 10 ms. Results. Mg2+ and Ca2+ (0.03125 mM) were contributed to reduce the intensity of optical absorption maxima of STQ-Cl by 1.6 and 1.3 times, respectively. The effect was most pronounced at 0.015625 mM Zn2+. Weak differences in the optical absorption of solutions were detected when STQ-NO2 was incubated with different concentrations of Mg2+ and Ca2+. The optical absorption intensity of the STQ-NO2 aqueous solution was increased at 0.015625 and 0.03125 mM Zn2+. The maximum cytotoxicity against MDA-MB-231 cells for STQ-Cl was about 80 %, and STQ-NO2 was 60 % at 0.04 mM Zn2+. DU-145 cells were more sensitive to STQ-NO2 (EC50 = 0.011 mM), but weakly sensitive to STQ-Cl (50 % at 0.125 mM). The maximum luminescence intensity was after 20 min of incubation with STQ-Cl and STQ-NO2 (5 mM) for both cells lines and was not change over time. Conclusions. The decrease of optical absorption maxima of STQ-Cl aqueous solutions in the presence of magnesium, calcium, and zinc cations was a consequence of aggregation processes. This phenomenon was probably the reason for the different cytotoxicity of STQ-Cl and STQ-NO2, as well as the presence of other mechanisms of action to cancer cells. Results was a consequence of different affinity of 8-hydroxyquinoline derivatives to magnesium, calcium and zinc cations, solubility in water, stability, aggregation of metal complexes and free compounds.

Application of Solid Dispersion Technology to Obtain a Model of Injectable Dosage Form of Indolocarbazole Derivative

Introduction. N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia synthesized an original derivative of indolocarbazole with the carbohydrate residue xylose, which has a pronounced cytotoxic and anti-angiogenic activity. The substance LCS-1269 is an amorphous powder that is almost insoluble in water, which causes difficulties in the development of an injectable dosage form (IDP). To solve this problem, a technological approach to obtain a solid dispersion (SD) of LCS-1269 has been proposed.Aim. To develop a model of IDP of the indolocarbazole derivative LCS-1269 based on SD.Materials and methods. We used a substance LCS-1269 synthesized in the Chemical Synthesis Laboratory of the N. N. Blokhin National Medical Research Center of Oncology. Emuxol 268, Kolliphor® P 188, Soluplus®, Lutrol® F68, Kollidon® 12 and Kollidon® 17, soybean phosphatidylcholine unsaturated S PC and saturated S PC-3 were investigated as carriers of the active substance. SD LCS-1269 was obtained by solvent removal: the active substance was dissolved in acetone, the carrier − in chloroform, the obtained solutions were mixed, transferred into a bottle and evaporated under vacuum (50 ± 5 mbar) in the desiccator at water bath temperature 65 ± 2 °С. To obtain aqueous solution of LCS-1269 dry mass was dissolved using different auxiliary substances or their mixtures: water for injection, ethanol 95 %, benzyl alcohol, Kollisolv® PEG 400, MONTANOX™ 80. To increase stability, the aqueous solution of LCS-1269 was lyophilized in an Edwards Minifast DO.2 freeze dryer.Results and discussion. Kollidon® 17 was chosen as the carrier material for the SD active substance. It was found that a clear solution of LCS-1269 with the concentration of the active substance 0.5 % was formed by dissolving the SD in ethanol 95 % and then gradually diluting the alcohol mixture with water for injection. In this case, the mass ratio of the components of the developed model IDF LCS : Kollidon® 17 : ethanol : water is 1 : 40 : 32 : 127. As a result of freeze-drying of the water-ethanol solution of LCS-1269 the IDF in the form of lyophilizate easily soluble in a 10 % solution of ethanol was obtained.Conclusion. An IDF model of the hydrophobic derivative of indolocarbazole LCS-1269 based on SD was developed and submitted for biological studies to evaluate its effectiveness.

Hydrophobic Melanin via Post-Synthetic Modification for Controlled Self-Assembly.

Allomelanin is a class of nitrogen-free melanin mostly found in fungi and, like all naturally occurring melanins, is hydrophilic. Herein, we develop a facile method to modify synthetic hydrophilic allomelanin to yield hydrophobic derivatives through post-synthetic modifications. Amine-functionalized molecules of various kinds can be conjugated to allomelanin nanoparticles under mild conditions with high loading efficiencies. Hydrophobicity is conferred by introducing amine-terminated alkyl groups with different chain lengths. We demonstrate that the resulting hydrophobic allomelanin nanoparticles undergo air/water interfacial self-assembly in a controlled fashion, which enables the generation of large-scale and uniform structural colors. This work provides an efficient and tunable surface chemistry modification strategy to broaden the scope of synthetic melanin structure and function beyond the known diversity found in nature.

Effect of Acyl Chain Length on Hydrophobized Cashew Gum Self-Assembling Nanoparticles: Colloidal Properties and Amphotericin B Delivery

Given its many potential applications, cashew gum hydrophobic derivatives have gained increasing attraction in recent years. We report here the effect of acyl chain length on hydrophobized cashew gum derivatives, using acetic, propionic, and butyric anhydrides on self-assembly nanoparticle properties and amphotericin B delivery. Nanoparticles with unimodal particle size distribution, highly negative zeta potential, and low PDI were produced. Butyrate cashew gum nanoparticles presented smaller size (&lt;~100 nm) than acetylated and propionate cashew gum nanoparticles and no cytotoxicity in murine fibroblast cells was observed up to 100 µg/mL for loaded and unloaded nanoparticles. As a proof of concept of the potential use of the developed nanoparticle as a drug carrier formulation, amphotericin B (AmB) was encapsulated and fully characterized in their physicochemical, AmB association and release, stability, and biological aspects. They exhibited average hydrodynamic diameter lower than ~200 nm, high AmB efficiency encapsulations (up to 94.9%), and controlled release. A decrease in AmB release with the increasing of the anhydride chain length was observed, which explains the differences in antifungal activity against Candida albicans strains. An excellent storage colloidal stability was observed for unloaded and loaded AmB without use of surfactant. Considering the AmB delivery, the acyl derivative with low chain length is shown to be the best one, as it has high drug loading and AmB release, as well as low minimum inhibitory concentration against Candida albicans strains.

Solution properties of hydrophobic derivatives of poly(ethylene-alt-maleic acid)

A library of hydrophobically modified polyelectrolytes was prepared by reacting linear alkyl amines with poly(ethylene-alt-maleic anhydride), followed by hydrolysis of the residual anhydride groups. Every reacted anhydride gives a pendent alkylamide plus a carboxylic acid group, and the result is a comb architecture. The lengths of the alkyl side chains were 3, 6, 8, or 10 carbons. The density of alkyl side chains was expressed as the fraction of anhydride groups reacted with alkyl amines (25 %, 50 %, and 75 %). The dominant factor influencing the aqueous solution properties is the alkyl chain length. C3 polymers had no pyrene receptive hydrophobic domains. C6 and C8 polymers bound pyrene at pH less than 6 and do not give reliable dynamic light scattering (DLS) results. C10 polymers displayed pyrene binding across the pH range and, based on DLS and AFM data, possibly appear as unimolecular nanogel dispersions from pH 7–9. At pH values > 9, our DLS measurements gave low-quality data, whereas at pH less than 7 both DLS and AFM results indicated nanogel aggregation. The C10 polymer properties were surprisingly insensitive to the degree of hydrophobic substitution over the range of 25–75 %. The nanogels with low alkyl contents were slightly more swollen and had high NaCl critical coagulation concentrations compared to the high alkyl content nanogels. These polymers are of particular interest because the non-derivatized maleic moieties in the polymers can form ester linkages to cellulose in an aqueous, catalyst-free process.

Novel HDL mimicking targeted drug delivery system for the treatment of Ewing Sarcoma

PurposeSince their discovery as antitumor agents, anthracycline drugs such as doxorubicin have remained mainstays as an important class of chemotherapy for the treatment of a wide range of cancers including pediatric malignancies like Ewing Sarcoma (EWS). Unfortunately, their usage is limited due to cumulative dose‐dependent cardiotoxicity. Targeted drug delivery could be an important option to circumvent this problem.Experimental designOur laboratory has developed a novel reconstituted HDL drug delivery system comprised of Myristic acid conjugated Apo AI mimicking 5A peptide (Myr5A). We used a hydrophobic derivative of doxorubicin, N‐Benzyladriamycin‐14‐valerate (AD198) to engineer formulations of Myr5A‐AD198. Physico‐chemical characterization including size, zeta potential and entrapment efficiency was determined. Cytotoxic effectiveness of this formulation was tested in Ewing Sarcoma cells A673 and Cardiomyocytes, H9c2 in 2D and 3D spheroid model using CCK‐8 assays. Using Myr5A based formulation‐containing BODIPY; mechanism of uptake of payload was demonstrated by imaging. In addition, we investigated Biodistribution and payload retention in EWS tumors in xenograft NOG mice with EWS tumor model.ResultsFormulation of the Myr5A‐AD198 was stable and non‐leaky with payload entrapment efficiency of 47.6 ± 3.2%. The nanoparticles were spherical with average size of 47 ± 12 nm as observed by transmission electron microscopy (TEM). Cytotoxicity assays demonstrated that IC50 values of Myr5A‐AD198 formulation was 2.8 ± 0.4 times more effective than free AD198 in EWS cells. On the other hand, 3 times more dose was required for Cardiomyocytes with Myr5A‐AD198 formulation as compared to free AD198. Blocking the Scavenger Receptor type B1 (SR‐B1) receptors, resulted in inhibition of the uptake of payload in Myr5A formulation. Subcutaneous injection of Myr5A‐IR 780 dye in xenograft NOG mice indicated the retention of payload for up to 72 hours in tumor.ConclusionThese preclinical studies indicated a great translational potential of Myr5A‐AD198 formulation for the treatment of EWS patients due to its selective uptake mechanism and cardio‐protective effect. Longer retention of the drug in tumors as well as lower dose requirement compared to free drug gives an additional advantage. In future, the Myr5A based technology shows promise for personalized treatment options in EWS and other type of cancers as well.

Identification of p-Coumaric Acid and Ethyl p-Coumarate as the Main Phenolic Components of Hemp (Cannabis sativa L.) Roots.

Hemp (Cannabis sativa L.) contains a variety of secondary metabolites, including cannabinoids, such as psychoactive (−)-trans-Δ⁹-tetrahydrocannabinol. The present study was conducted to identify the major phenolic components contained in hemp root, which has been relatively under-researched compared to other parts of hemp. The aqueous ethanol extract of hemp roots was fractionated into methylene chloride (MC), ethyl acetate (EA), and water (WT) fractions, and high-performance liquid chromatography with photodiode array detection (HPLC-DAD) analysis was performed. The main ultraviolet (UV)-absorbing phenolic compound contained in the EA fraction was identified as p-coumaric acid by comparing the retention time and UV absorption spectrum with a standard. Silica gel column chromatography was performed to isolate a hydrophobic derivative of p-coumaric acid contained in the MC fraction. Nuclear magnetic resonance (NMR) analysis identified the isolated compound as ethyl p-coumarate. For comparative purposes, ethyl p-coumarate was also chemically synthesized by the esterification reaction of p-coumaric acid. The content of p-coumaric acid and ethyl p-coumarate in the total extract of hemp root was estimated to be 2.61 mg g−1 and 6.47 mg g−1, respectively, by HPLC-DAD analysis. These values correspond to 84 mg Kg−1 dry root and 216 mg Kg−1 dry root, respectively. In conclusion, this study identified p-coumaric acid and ethyl p-coumarate as the main phenolic compounds contained in the hemp roots.