Hydrophilic End Research Articles

Electrical Conductivity Enhancement and Electronic Applications of 2D Ti3C2Tx MXene Materials

AbstractIn the past 10 years, MXene (transition metal carbides, nitrides, and carbonitrides), a 2D nanomaterial, has become one of the research hotspots with its hydrophilic ends, solution machinability, and excellent electronic, mechanical, and optical characteristics. Herein, recent progress on Ti3C2Tx MXene materials is reviewed, analyzed, and evaluated with highlights on their electrical performances and applications. The progress on electrical conductivity enhancement of Ti3C2Tx MXene is carefully reviewed from a number of aspects in Ti3AlC2 MAX phase precursor, synthesis methods, delamination treatment, removal of delamination compounds, surface terminations, thin‐film deposition methods, and storage environment and time. Finally, a summary is provided and the challenges are discussed to further enhance the electrical conductivity.

Single and mixed Pluronics® micelles with solubilized hydrophobic additives: Underscoring the aqueous solution demeanor and micellar transition

This work aims to optimize the aqueous solution behavior in mixed system of polyethylene oxide-block-polypropylene oxide-block-polyethylene oxide (PEO-PPO-PEO). Two copolymers viz., P123 and F127 (with same size of hydrophobic PPO block and 30 % and 70 % hydrophilic PEO end blocks, respectively) were used and the changes in size self-assembled mixed micelles were examined in the presence of small amount of four very hydrophobic copolymers viz., L61, L81, L101, and L121 (each with 10 % PEO but varying PPO molecular weight). The cloud point (CP) show the changes in the phase behavior of the examined systems while the relative viscosity (ηrel) pointed out marked changes in the flow behaviour. The micellar characteristics (size, shape, aggregation number) determined by dynamic light scattering (DLS) and small-angle neutron scattering (SANS) depict the plausible morphological transition expressed as apparent hydrodynamic diameter (Dh), hard sphere radius (Rhs), aggregation number (Nagg) at different temperatures. Such modulations in the mixed Pluronics® systems are further examined for the solubilization of hydrophobic anticancer drug curcumin (Cur). The enhanced Cur solubility is well-established from the distinctive peak intensities as observed from UV–Visible (UV–vis) and Fourier Transform Infrared (FT-IR) spectral profile which validated the interaction of Cur with the examined copolymeric systems.

Self-Propelled Aero-GaN Based Liquid Marbles Exhibiting Pulsed Rotation on the Water Surface.

We report on self-propelled rotating liquid marbles fabricated using droplets of alcoholic solution encapsulated in hollow microtetrapods of GaN with hydrophilic free ends of their arms and hydrophobic lateral walls. Apart from stationary rotation, elongated-spheroid-like liquid marbles were found, for the first time, to exhibit pulsed rotation on water surfaces characterized by a threshold speed of rotation, which increased with the weight of the liquid marble while the frequency of pulses proved to decrease. To throw light upon the unusual behavior of the developed self-propelled liquid marbles, we propose a model which takes into account skimming of the liquid marbles over the water surface similar to that inherent to flying water lily beetle and the so-called helicopter effect, causing a liquid marble to rise above the level of the water surface when rotating.

Continuous gradient temperature Raman spectroscopy of 1-stearoyl- 2-docosahexaenoyl, 1-stearoyl- 2-arachidonoyl, and 1,2-stearoyl phosphocholines

Mixed chain phospholipids containing a saturated fatty acid at sn1 and a polyunsaturated fatty acid in sn2 are common in the specialized biological membranes prevalent in neural, retinal and organ tissues. Particularly important are mixed lipids containing palmitic or stearic acid and arachidonic or docosahexaenoic acid. Gradient temperature Raman spectroscopy (GTRS) applies the temperature gradients utilized in differential scanning calorimetry to Raman spectroscopy, providing a straightforward technique to identify molecular rearrangements and phase transitions. Herein we utilize GTRS for 1-18:0, 2-20:4n-6 PC; 1-18:0 2-22:6n-3 PC; and 1-18:0, 2-18:0 PC from −80 to 50 °C temperatures. 20 Mb three-dimensional data arrays with 0.2 °C increments and first/second derivatives allowed detailed vibrational mode assignment and analysis. Samples were analyzed neat and with molecular hydration. Previously reported phase transitions for hydrated 18:0−20:4PC and 18:0−22:6PC and numerous spectral differences resulting from hydration and the double bond structure were clearly observed. Molecular models showed that the addition of minimal water molecules results in significant structural differences compared to the neat molecules; 18:0−22:6PC is strikingly compact with water when viewed from the hydrophilic end. This precise Raman data cannot be observed in typically utilized fully hydrated vesicle samples, however the improved GTRS will allow for more precise analysis in fully hydrated vesicles because the underlying modes in the unavoidably broadened spectra can be identified.

A supramolecular complex of hydrazide-pillar[5]arene and bisdemethoxycurcumin with potential anti-cancer activity

Pillar[5]arene complexes of the naturally occurring compound bisdemethoxycurcumin (BDMC) were acquired for improving the water solubility and stability of BDMC. As a family member of curcuminoid compounds, BDMC has many interesting therapeutic properties. However, its low aqueous solubility and stability resulted in poor availability and restricted the clinical efficacy. Pillar[5]arenes with hydrophilic ends and a hydrophobic cavity could include with BDMC based on size matching. The synthesized hydrazide-pillar[5]arene (HP5A) and BDMC had a strong host–guest interaction with a 1:1 binding stoichiometry. Furthermore, the HP5A ⊃ BDMC complex could self-assemble into well-defined fibers in water/ethanol solution. This supramolecular complex worked well in vitro for inhibiting the proliferation of hepatoma carcinoma cells HepG2. Remarkably, this method of complexation with pillar[5]arenes visibly reduced the undesirable side effects on normal cells without weakening the anti-cancer activity of the drugs. We expected that the obtained host–guest complex and fibrous assembly would provide a promising platform for delivering drugs with low water solubility.

RGD-targeted redox responsive nano micelle: co-loading docetaxel and indocyanine green to treat the tumor

Cancer, also known as a malignant tumor, has developed into a type of disease with the highest fatality rate, seriously threatening the lives and health of people. Chemotherapy is one of the most important methods for the treatment of cancer. However, chemotherapy drugs have some problems, such as low solubility and lack of targeting, which severely limit their clinical applications. To solve these problems, we designed a block copolymer that has a disulfide bond response. The polymer uses RGD peptide (arginine-glycine-aspartic acid) as the active targeting group, PEG (polyethylene glycol) as the hydrophilic end, and PCL (polycaprolactone) as the hydrophobic end. Then we utilized the amphiphilic polymer as a carrier to simultaneously deliver DOC (docetaxel) and ICG (indocyanine green), to realize the combined application of chemotherapy and photothermal therapy. The antitumor efficacy in vivo and histology analysis showed that the DOC/ICG-loaded micelle exhibited higher antitumor activity. The drug delivery system improved the solubility of DOC and the stability of ICG, realized NIR-guided photothermal therapy, and achieved an ideal therapeutic effect.

Experimental and molecular dynamics study into the surfactant effect upon coal wettability.

In order to improve the wettability and permeability of coal seams, the water injection efficiency of coal seams has to be boosted, the amount of dust generation has to be reduced, and coal and gas outburst must be prevented, and a surfactant is used to modulate the coal surface wettability. In this work, taking coal samples from Pingdingshan mine in Henan as the research object, their surface chemistry was initially scrutinized and then coal surface engineering via surfactants was inspected by a contact angle test. The coal wettability was ameliorated with surfactants, particularly using the 1 wt% non-ionic surfactant Triton X-100, which elicited a 47% lower contact angle than the raw coal. The surface free energy of the coal sample modified by 1.0 wt% Triton X-100 was increased from 44.51 mN m−1 to 49.52 mN m−1. The microstructural characteristics of coal samples allowed leveraging the Wiser model to construct three kinds of surfactant-coal adsorption models to dissect the adsorption configuration of the system. The results indicate that the addition of surfactants increases both the interaction of water with the coal and the diffusion coefficient of water molecules, resulting in the coal surface transformation from hydrophobicity to hydrophilicity. Our current work can provide salutary guidance and reference for coal water injection and dust suppression.

Short self‐assembling peptides with a urea bond: A new type of supramolecular peptide hydrogel materials

AbstractThere is an increasing need to develop short self‐assembling peptides (SAPs) that can form hydrogels for cell engineering and biomedical applications. In this study, we proposed new short self‐assembling peptides with a symmetric structure via a urea bond. (FFiO)2 and (FFiK)2 were designed as amphiphilic peptides with a hydrophobic domain inside of zwitterionic hydrophilic ends and a urea bond embedded in the hydrophobic domain. The two peptides were synthesized by a liquid‐phase method. The simple structural design of these peptides makes their synthesis on a large scale possible. Both (FFiO)2 and (FFiK)2 assembled into β‐sheet structure and formed stable hydrogels under physiological pH conditions in a pH‐responsive manner. The urea bond was important for the formation of transparent hydrogels. Since (FFiK)2 exhibited self‐assembling properties superior to those of (FFiO)2, (FFiK)2 hydrogels were used as scaffolds for cell culture. (FFiK)2 hydrogels supported cell proliferation without significant cytotoxicity. Therefore, (FFiK)2 is a beneficial supramolecular peptide hydrogelator for cell engineering.

Biosurfactants as a Novel Additive in Pharmaceutical Formulations: Current Trends and Future Implications.

Surfactants are an important category of additives that are used widely in most of the formulations as solubilizers, stabilizers, and emulsifiers. Current drug delivery systems comprise of numerous synthetic surfactants (such as Cremophor EL, polysorbate 80, Transcutol-P), which are associated with several side effects though used in many formulations. Therefore, to attenuate the problems associated with conventional surfactants, a new generation of surface-active agents is obtained from the metabolites of fungi, yeast, and bacteria, which are termed as biosurfactants. In this article, we critically analyze the different types of biosurfactants, their origin along with their chemical and physical properties, advantages, drawbacks, regulatory status, and detailed pharmaceutical applications. 243 papers were reviewed and included in this review. Briefly, Biosurfactants are classified as glycolipids, rhamnolipids, sophorolipids, trehalolipids, surfactin, lipopeptides & lipoproteins, lichenysin, fatty acids, phospholipids, and polymeric biosurfactants. These are amphiphilic biomolecules with lipophilic and hydrophilic ends and are used as drug delivery vehicles (foaming, solubilizer, detergent, and emulsifier) in the pharmaceutical industry. Despite additives, they have some biological activity as well (anti-cancer, anti-viral, anti-microbial, P-gp inhibition, etc.). These biomolecules possess better safety profiles and are biocompatible, biodegradable, and specific at different temperatures. Biosurfactants exhibit good biomedicine and additive properties that can be used in developing novel drug delivery systems. However, more research should be driven due to the lack of comprehensive toxicity testing and high production cost which limits their use.

Improved Affinity of Nanoscale Zero Valent Iron toward Hydrophobic Organic Solvent using Poly(1-vinylpyrrolidone-co-vinyl acetate)

Objectives : Levels of organic contaminants in excess of the standard minimum have been detected in many commercial and residential sites, and the severity of soil and groundwater pollution is increasing. In particular, non-aqueous phase liquids (NAPLs) are hydrophobic organic pollutants that do not mix with water and are difficult to remove with existing soil remediation technology. These pollutants slowly dissolve into the groundwater over long periods of time, thus contaminating the groundwater. With the increasing need to remove NAPLs for soil and groundwater remediation, widespread interest has focused on the use of nanoscale zero valent iron (nZVI). However, nZVI has the disadvantage of reduced subsurface mobility. Hence, in the present study, the nZVI surface is modified with poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP/VA), which has both hydrophilic and hydrophobic groups, to improve the mobility and selectivity of nZVI for the removal of NAPL.Methods : The PVP/VA modified nZVI is synthesized through the reaction of FeSO4･7H2O and NaBH4 in the presence of PVP/VA. To confirm the dispersibility of the prepared material, a precipitation experiment is performed using a visible light spectrometer, and the mobility through a sand-filled column is evaluated. In addition, the variation in particle size and characteristics according to the presence of PVP/VA is examined via transmission electron microscopy. The nitrate reduction ability of nZVI with PVP/VA is also evaluated to reveal changes in reactivity depending upon the degree of dispersion. To confirm the selective mobility towards NAPL, trichloroethylene and dodecane are used to evaluate the mobility with and without PVP/VA. Finally, the ratio of nZVI passing through the sponge layer absorbing dodecane is evaluated to determine the selective mobility towards NAPL in the porous medium.Results and Discussion : Although the dispersibility of the PVP/VA-nZVI is not significantly changed, the particle size is significantly decreased. Both the mobility in porous media and the nitrate reduction rate are improved via PVP/VA modification. The affinity for hydrophobic contaminants and the selective migration of PVP/VA-nZVI towards the NAPL layer are also improved. The high affinity for the NAPL was also shown by the column with NAPL layer.Conclusions : Surface-modification with PVP/VA, which has both hydrophilic and hydrophobic ends, enabled the synthesis of nZVI with a smaller and more uniform particle size, thus providing high mobility in porous media and high reactivity towards contaminants. The combined hydrophilicity and hydrophobicity of PVP/VA is shown to increase the affinity of nZVI towards NAPL and, thus, promote its migration to the NAPL layer. Thus, it is anticipated that the efficiency of soil remediation can be improved by promoting the movement of nZVI towards the target NAPL layer.

Polymerizable Hydrophobically Modified Ethoxylated Urethane Acrylate Polymer: Synthesis and Viscoelastic Behavior in Aqueous Systems

Hydrophobically modified ethoxylated urethanes (HEURs) comprising hydrophilic poly(ethylene glycol) backbone and hydrophobic end groups are widely applied as rheological additives to regulate the viscoelastic behavior of waterborne systems such as coatings and inks. However, the conventional HEURs are usually nonreactive and remain free in final films, which may bring some defects and damages to the final cured films during the service time. An appealing way to improve filming properties may be to design reactive HEURs, which can participate in the post-crosslinking reactions with other components in formula during the film curing. In this work, a polymerizable acrylic-type HEUR (acrylic-HEUR) end-functionalized by the reactive methacrylate group and hydrophobic octadecyl tail is reported. The typical free radical polymerization feature of acrylic-HEUR based on the highly reactive methacrylate group is carefully clarified by dynamic light scattering, in situ nuclear magnetic resonance (1H NMR), and rheological measurements. The excellent thickening performance of acrylic-HEUR in waterborne UV emulsions and its effective copolymerization reactivity with the UV-curable matrix resin are demonstrated by in situ rheological measurements under UV irradiation in detail. Compared to conventional nonreactive HEURs, the copolymerization reactivity of acrylic-HEUR may make it especially suitable for applications in waterborne UV coatings to avoid its migration from final UV-cured films. This work may not only open a new perspective for the fabrication of HEUR polymers with high chemical reactivity but also promise the potential of polymerizable HEURs as superior associative thickeners in industry.

Synthesis of amphiphilic Janus dendrimer and its application in improvement of hydrophobic drugs solubility in aqueous media

Classic dendrimers are not used in many specific applications such as simultaneous loading of different drugs due to the existence of identical end groups. The possibility of designing the structure in dendrimers paves the way to synthesize more complicated dendrimers. This includes the creation of various types of peripheral groups on the surface of dendrimers to synthesize for example Janus dendrimers. Nowadays, three main methods are proposed for the synthesis of Janus dendrimers in which the high amount of conventional dendrimers is produced. The goal of this work is to develop a new method for synthesis of Janus dendrimers without production of conventional dendrimers. The present method has three main stages for the synthesis of Janus dendrimers including synthesis of 5th generation PPI dendrimer with cystamine core and hydrophobic surface, conversion of disulfide bonds to thiol group using a structure scission approach, and the formation of PAMAM hydrophilic dendrons with amine end groups. Different analyses including FT-IR, NMR, DLS, and GPC are used to prove the success of the synthesis route. Also, due to application of dendrimers in drug delivery including solubility improvement of hydrophobic drugs, Janus dendrimers are used to improve solubility of tetracycline and dexamethasone in presence of different generations of Janus dendrimers. Since the Janus dendrimers have both hydrophilic and hydrophobic ends, as well as having numerous terminal groups and numerous internal cavities, they have resulted in significant improvements in drug solubility. Also, solubility of the two hydrophobic drugs in water was increased by increasing concentration and generation of dendrimer.

Investigating the Synergistic Anionic/Nonionic Surfactant Interaction on Nanoparticle Synthesis with Solvent-Free Extrusion Emulsification

This paper examines different binary mixtures of anionic/nonionic surfactants using a new technique known as solvent-free extrusion emulsification (SFEE) to control the surface charge in resulting nanosized polyester particles. Five similar nonionic surfactants with only minor structural differences from one another, along with an anionic surfactant (Calfax DB-45), were considered. The optimal hydrophilic end for the nonionic species was found to be 10–12 ethoxy units, whereas with respect to their hydrophobic end group, a more hindered branched alkyl structure was more desirable in preparing particles in the desired size range of 100–200 nm for this polymer. The preferred blend of Calfax/Igepal CA-630, found in a preliminary study, was shown to exhibit a synergistic interaction in SFEE in subsequent trials. The synergistic interaction was considered to arise from the high viscosity of the system, keeping the two surfactants partitioned across the interface of the emulsifying phases, which allowed a lower total surfactant concentration to be used than possible in a comparable solvent-based emulsification method. This partitioning across the interface decreased the nonextractable amount of Calfax left in the polyester latex. This approach of blending anionic and nonionic species shows an important step in preparing nanosized particles with controlled charge.

Micellar thermodynamics of voriconazole cyclodextrin-HS15 complex in glucose and NaCl solution

The hydrodynamic radius and size dispersion of cyclodextrin-micelle complexes loaded with voriconazole in glucose and NaCl solutions were studied in detail by dynamic light scattering technique. The critical micelle concentration (CMC) was determined by surface tension, and the relevant air–water interface parameters and micellization thermodynamic parameters were calculated. In the environment of glucose and NaCl, the CMC value decreases with the increase in the concentration of the additive. Glucose forms more stable hydrophilic ends by binding to the micelle hydrophilic group. NaCl acts as a water structure building ion to provide hydrophobic force to the gum surfactant molecules and promote the formation of micelles. The results of insoluble particles are consistent with the CMC results, which further supports the results obtained.

Comparative Investigation on the Soil Burial Degradation Behaviour of Polymer Films for Agriculture before and after Photo-Oxidation

Polymer films based on biodegradable polymers, polyethylene (PE) and modified PE with oxo-degradable additive were prepared by film blowing. Carbon black (1%) was added to all the films. Commercial biodegradable Ecovio® and Mater-Bi® samples were used. Mechanical properties, soil burial degradation and surface wettability were investigated, before and after UV irradiation. Chemical modifications induced by UV and soil degradation, or a synergic effect, were highlighted by Attenuated Total Reflection-Fourier Transform Infra-Red (ATR-FTIR). Photo-oxidized film samples with an elongation at break equal to 50% and 0.5 the initial value were selected for the soil burial degradation test at 30 °C. Weight loss measurements were used to follow biodegradation in soil. Predictably, the degradation in soil was higher for biodegradable polymer-based films than for the PE-based ones. UV irradiation increased surface wettability and encouraged the disintegration in soil of all the samples. In fact, photo-oxidation produced a molar mass reduction and hydrophilic end groups, thus increasing surface erosion and weight loss. This paper not only supplies new criteria to evaluate the performance of biodegradable films in agriculture, before and after lifetime, but also provides a comparative analysis on the soil burial degradation behaviour with traditional ones.

Amphotericinb Interaction with DMPC/ERGO Mixed Lipid Bilayers

Amphotericin B is a novel antibiotic with hydrophilic and hydrophobic ends. It can form a complex structure with sterol in the membrane. It has a good antibacterial or bactericidal effect, and it can inhibit the growth of most fungi. Although it has been used in medicine, its mechanism of action is still unclear. We used X-ray diffraction technology to measure the structure of the lipid bilayer membrane. The ergosterol and DMPC were fixed at a concentration ratio (E/L) of 1/20 and 1/40. We measured the structural changes of the lipid bilayer membrane after the addition of amphotericin B. We have found that ergosterol causes a thickening effect in DMPC and thickening as the concentration increases. However, amphotericin B causes a thinning effect in DMPC and becomes thinner as the concentration increases. The results showed that when the concentration of amphotericin B increased to A/E=1/2, the thinning effect of the two mixed lipid membranes turned into thickening. It was found that in E/L=1/20 and 1/40 mixed lipid membranes, this phenomenon occurs when the concentration of amphotericin B reaches A/L∼1/50 and 1/100. This indicates that in the two mixed lipid membranes, the concentration ratio of amphotericin B to ergosterol is higher than 1/2, and the amphotericin B and ergosterol complex will produce a state changed in the membrane. From the molecular structure model analysis, it can be inferred that this concentration has the opportunity to change the amphotericin B from the surface state to the inserted state.

Biomimetic Transmembrane Signal Transducing DNA Nanosensor for Membrane Enclosed Nucleic Acid Biomarker Detection

Signal transduction across phospholipid bilayer is an important process in biology that allows cells to respond to changes in their external environment and communicate among cells. Trans-bilayer signal transduction by sophisticated membrane proteins such as G-protein coupled receptors (GPCR) play crucial role in regulating key physiological processes. Being able to mimic the signal transduction by GPCRs has enormous opportunity in synthetic biology for potential application in artificial tissue signaling, biosensing and controlled drug delivery. In a general sense, GPCRs consist of a dynamically reconfigurable, hydrophilic-hydrophobic-hydrophilic (Hi-Ho-Hi) molecular structure where the hydrophobic part is buried in the lipid bilayer while the two hydrophilic ends remain on the two sides of the bilayer. In this research, we mimic the Hi-Ho-Hi molecular design principle of GPCRs to create a DNA-based transmembrane Nano-Sensor (TraNS) that dynamically reconfigures upon sensing a membrane-enclosed nucleic acid target. Four interwoven DNA strands are self-assembled to form each TraNS device. Two hydrophobic cholesterol anchors are covalently conjugated to create a hydrophobic belt around each TraNS device to help it to span the lipid bilayer, similar to the Hi-Ho-Hi nature of GPCRs. We design the TraNS device such that after insertion to lipid bilayer, it selectively switches from a closed to an open state upon sensing a nucleic acid target encapsulated inside the membrane. Gel electrophoresis and fluorescence spectra confirms the formation and configurational switch of the TraNS device. Next, we demonstrate the use of the TraNS device for biosensing application by detecting presence of non-small cell lung cancer specific micro-RNA: miR-21-5p in exosomes. We believe this is the first demonstration of mimic of a transmembrane signal transducing protein using DNA nanostructures and use of the nanostructure towards diagnostic application.

Surface modification enhances interfacial bonding in PLLA/MgO bone scaffold.

The poor interfacial bonding and resultant agglomeration of nanoparticles in polymer-based composite severely deteriorated their reinforcement effect. In this work, MgO nanoparticles (MgO-NPs) were surface modified with Poly (L-lactic acid-co-malic acid) (PLMA) to improve the interfacial compatibility in Poly-l-lactic acid (PLLA) scaffold manufactured by selective laser sintering. PLMA possess a hydrophilic end with carboxyl group (comes from the malic acid) and an l-lactic acid chain. On one hand, the carboxyl group was able to form hydrogen bonding with the hydroxyl groups of MgO-NPs. On the other hand, the l-lactic acid chain containing the hydroxyl groups could react with the carboxyl group of PLLA. Results revealed that the scaffold exhibited significantly enhanced compressive strength and modulus by 47.1% and 237.7%, respectively, which could be ascribed to the enhanced interfacial bonding between PLLA and MgO-NPs, as well as the rigid particle reinforcement. In addition, the scaffold was favorable for cell adhesion, proliferation and differentiation, owing to the improved hydrophilic and suitable pH environment. It was suggested the scaffold was a promising material for bone repair application.

Enhancing membrane modulus of giant unilamellar lipid vesicles by lateral co-assembly of amphiphilic triblock copolymers

We report a facile, but robust approach to fabricate structurally stable giant unilamellar vesicles (GUVs), on which a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer membrane was made rigid by introducing amphiphilic block polymers. Particularly, we found that lateral co-assembly of an amphiphilic triblock copolymer (ATC) structured with a hydrophobic middle block and long molecular weight (20 K g/mol) hydrophilic end blocks remarkably enhanced the stretching modulus (k) of GUVs. When the membrane composition was optimized, the k value of ATC-hybridized GUVs increased to 6.2 × 108 Pa, which was approximately 10-fold higher than that of DPPC GUVs, thus leading to a much longer half-life. Moreover, we demonstrated that our ATC-hybridized GUVs enabled development of a fascinating vesicular model, which shows great potential as a structurally stable cell membrane mimic.

Safety, tolerability, and pharmacokinetics of adamgammadex sodium, a novel agent to reverse the action of rocuronium and vecuronium, in healthy volunteers

Neuromuscular blockers (NMBs) selectively block neuromuscular transmission at the N2-nicotinic receptor on motor neurons to paralyze skeletal muscles, and are mainly used to facilitate tracheal intubation and surgical procedures. Rapid reversal is necessary in clinical practice to avoid profound block and reduce recovery time. Adamgammadex sodium is a modified γ-cyclodextrin derivative consisting of a lipophilic core and a hydrophilic outer end that forms an inactive tight inclusion complex with free molecules of rocuronium and vecuronium. In preclinical study, adamgammadex produced a concentration-dependent reversion effect of neuromuscular blockade induced by rocuronium in beagle dogs. Furthermore, adamgammadex had a less potential side effects than sugammadex and other clinical used neuromuscular block antagonists. In this study, the objective was to assess the safety, tolerability, and pharmacokinetics of single intravenous injection of adamgammadex in healthy volunteers. Approved by the China Food and Drug Administration, 52 healthy volunteers (half male and half female) were enrolled in this single-center, randomized, double-blind placebo-controlled study. No serious adverse effects were happened in this study. The overall frequency of adverse effects in adamgammadex was similar for that in placebo, and there was no specific adverse effect in adamgammadex. All of the volunteers bearing the adverse effects were recovered to normal without any treatment or intervention. In pharmacokinetic study, the value of half-time, Tmax, and clearance were not changed significantly, and the Cmax and AUC0–∞ increased with a similar ratio of the escalating doses. For dose proportionality analysis of adamgammadex, the estimate of slope was close to 1, and it was not significantly different from 1 after doses (AUC0-∞, 0.9965 [90%CI, 0.9468, 1.046]; Cmax, 0.9462 [90%CI, 0.8800, 1.012]). Therefore, adamgammadex exposure in plasma increased in a dose- proportional manner. The urinary route is a significant excretory pathway for adamgammadex, and it is mostly completed at 8 h. All the results in this study showed that adamgammadex may be a novel safe neuromuscular blockade reversal agent .