Amphiphilic Moieties Research Articles

Membrane Permeability and Drug Targeting Potential of Phospholipid‐Based Nanocarriers in Lung Cancer Therapy

AbstractLung cancer has become the leading cause of cancer‐related deaths, surpassing all other forms of cancer. Among lung cancers, non‐small cell lung cancer (NSCLC) accounts for approximately 85% of cases. The use of tobacco, genetic traits, and radiation exposure are amongst the major reasons of lung cancer. The ongoing research in the medical field has considered the efficacy of nanocarriers in targeting various cancer cells. Among several biomaterials, lipid‐based nanocarriers have gained special attention due to their excellent compatibility, improved targeting efficacy, and encapsulation ability of diverse therapeutic agents. Phospholipids are naturally occurring amphiphilic moieties found in all living creatures. The presence of phospholipids in biomembrane aids the permeability of phospholipid‐based drug carrier. It can also facilitate targeting of therapeutic agents to cancer microenvironment without degrading the encapsulated drug. Phospholipids can be employed to develop conjugated nanocarriers and vesicular nanoformulation that can result in prolonged circulatory half‐life and controlled release of drugs. Phospholipids are also suitable biomaterials to attach a ligand for tissue‐specific targeting. Recent researches have reported effective targeting of chemotherapeutic agents, genes, and vaccines through phospholipid‐based nanocarriers to lung cancer cells. This review focuses on the rationality and applications of phospholipid‐based nanocarriers in lung cancer therapy.

Gemini cationic surfactant of 1, 3-bis (dodecyl dimethyl ammonium chloride) propane as a novel excellent inhibitor for the corrosion of cold rolled steel in HCl solution

Gemini surfactants have become the research focus of novel excellent inhibitors because of their special structure (two amphiphilic moieties covalently connected at head group by a spacer) and excellent surface properties. It is proved by theoretical calculations that 1, 3-bis (dodecyl dimethyl ammonium chloride) propane (BDDACP) molecules can perform electron transfer with Fe (110). And it has a small fraction free volume, thus greatly reducing the diffusion and migration degree of corrosive particles. The potentiodynamic polarization curve showed that coefficients of cathodic and anodic reaction less than 1 and polarization resistance increased to 1602.9 Ω cm−2 after added BDDACP, confirming that BDDACP significantly inhibited the corrosion reaction by occupying the active site. The electrochemical impedance spectrum of imperfect semi-circle shows that the system resistance increases and double layer capacitance after added BDDACP. Weight loss tests also confirmed that BDDACP forms protective film by occupying the active sites on steel surface, and the maximum inhibition efficiency is 92 %. Comparison of the microscopic morphology showed that steel surface roughness was significantly reduced after added BDDACP. The results of time-of-flight secondary ion mass spectrometry show that steel surface contains some elements from BDDACP, which confirms the adsorption of BDDACP on steel surface.

Designing Bio-Inspired Wet Adhesives through Tunable Molecular Interactions

Marine organisms, such as mussels and sandcastle worms, can master rapid and robust adhesion in turbulent seawater, becoming leading archetypes for the design of underwater adhesives. The adhesive proteins secreted by the organisms are rich in catecholic amino acids along with ionic and amphiphilic moieties, which mediate the adaptive adhesion mainly through catechol chemistry and coacervation process. Catechol allows a broad range of molecular interactions both at the adhesive-substrate interface and within the adhesive matrix, while coacervation promotes the delivery and surface spreading of the adhesive proteins. These natural design principles have been translated to synthetic systems toward the development of biomimetic adhesives with water-resist adhesion and cohesion. This review provides an overview of the recent progress in bio-inspired wet adhesives, focusing on two aspects: (1) the elucidation of the versatile molecular interactions (e.g., electrostatic interactions, metal coordination, hydrogen bonding, and cation-π/anion-π interactions) used by natural adhesives, mainly through nanomechanical characterizations; and (2) the rational designs of wet adhesives based on these biomimetic strategies, which involve catechol-functionalized, coacervation-induced, and hydrogen bond-based approaches. The emerging applications (e.g., tissue glues, surgical implants, electrode binders) of the developed biomimetic adhesives in biomedical, energy, and environmental fields are also discussed, with future research directions proposed.

Injectable polydimethylsiloxane microfiller coated with zwitterionic polymer for enhanced biocompatibility

Silicone-based fillers have been applied in several branches of medicine, such as soft tissue augmentation, because of their stability and durability. However, the inherently hydrophobic surfaces of silicone occasionally cause excessive deposition of the fibrous matrix in vivo, leading to severe fibrosis. In this study, we evaluated the use of a zwitterionic copolymer to offer a facile surface treatment method for silicone-based fillers and performed a preclinical trial of the formulation as-prepared. The copolymer has amphiphilic moieties, which act as macromolecular surfactants that can functionalize and stabilize the silicone particles during fabrication. The effectiveness and safety of the particle filler were evaluated histologically by scoring the peri-implant tissues into previously defined categories. Our results suggest that zwitterion-coated silicone fillers can inhibit protein adsorption, and thus, help attenuate foreign body reactions in a rat model. This demonstrates their potential for wide application in different fields within the discipline of medicine.

New Lipophilic Fluorescent Dyes for Labeling Extracellular Vesicles: Characterization and Monitoring of Cellular Uptake.

PKH dyes, which are currently the most widely used fluorescent probes for extracellular vesicle (EV) labeling, have some limitations. For example, these dyes tend to aggregate, leading to formation of EV-like nanoparticles that can be taken up by cells. Moreover, it has been suggested that PKH dyes trigger an enlargement of EVs because of membrane fusion or intercalation. To overcome these limitations, we developed three novel extracellular vesicular-membrane-binding fluorescent probes-Mem dye-Green, Mem dye-Red, and Mem dye-Deep Red-for monitoring EV uptake into cells. The dyes contain a cyanine group as a fluorescent scaffold and amphiphilic moieties on the cyanine. The three dyes have different photophysical characteristics. To investigate the characteristics of the Mem dyes for EV labeling, we performed nanoparticle tracking, zeta potential measurements, and confocal microscopy. The dyes enable highly sensitive fluorescence imaging of EVs. They can also be used to observe EV dynamics in live cells. The Mem dyes show excellent EV labeling with no aggregation and less particle enlargement.

Critical Amphiphilic Concentration: Effect of the Extent of Amphiphilicity on Marine Fouling-Release Performance

Amphiphilic surfaces, containing both hydrophilic and hydrophobic domains, offer desirable performance for many applications such as marine coatings or anti-icing purposes. This work explores the effect of the concentration of amphiphilic moieties on converting a polyurethane (PU) system to a coating having fouling-release properties. A novel amphiphilic compound is synthesized and added at increasing amounts to a PU system, where the amount of the additive is the only variable in the study. The additive-modified surfaces are characterized by a variety of techniques including ATR-FTIR, XPS, contact angle measurements, and AFM. Surface characterizations indicate the presence of amphiphilic domains on the surface due to the introduction of the self-stratifying amphiphilic additive. The fouling-release properties of the surfaces are assessed with three biological assays using Ulva linza, Cellulophaga lytica, and Navicula Incerta as the test organisms. A change in the fouling-release performance is observed and plateaued once a certain amount of amphiphilicity is attained in the coating system, which we call the critical amphiphilic concentration (CAC).

Amphiphilic phospholipid-iodinated polymer conjugates for bioimaging.

Amphiphilic phospholipid-iodinated polymer conjugates were designed and synthesized as new macromolecular probes for a highly radiopaque and biocompatible imaging technology. Bioconjugation of PEG 2000-phospholipids and iodinated polyesters by click chemistry created amphiphilic moieties with hydrophobic polyesters and hydrophilic PEG units, which allowed their self-assemblies into vesicles or spiked vesicles. More importantly, the conjugates exhibited high radiopacity and biocompatibility in in vitro X-ray and cell viability measurements. This new type of bioimaging contrast agent with a Mn value of 11 289 g mol-1 was found to have a significant X-ray signal at 3.13 mg mL-1 of iodine equivalent than baseline and no cytotoxicity after 48 hours incubation of with HEK and 3T3 cells at 20 μM (20 picomoles) concentration of conjugates per well. The potential of adopting the described macromolecular probes for bioimaging was demonstrated, which could further promote the development of a field-friendly and highly sensitive bioimaging contrast agent for point-of-care diagnostic applications.

Cubosome: A Potential Liquid Crystalline Carrier System.

Cubosome is a biocompatible, thermodynamically stable and bioadhesive drug carrier that is prepared from certain amphiphilic lipids and surfactants when mixed in a definite ratio. Structurally, they are selfassembled nano-constructed liquid crystalline particles comprising three-dimensionally arranged bicontinuous as well as nonintersecting lipid bilayers that give them a honeycomb-like appearance. Morphological characterization through SAXS (small-angle X-ray scattering) and cryo-TEM (cryo-transmission electron microscopy) revealed that they are square and round shaped particles in the nanometer range. These carriers have two separate aqueous regions and a large interfacial area that allow them to carry a variety of bioactive molecules having hydrophobic, hydrophilic or amphiphilic behavior. One of either two strategies i.e., top-down or bottom-up methods can be adopted to prepare these cubic structures. A number of dispersion techniques like sonication, spray drying, high-pressure homogenization or spontaneous emulsification can be adopted to prepare cubosomes. Their characteristics and benefits like multicompartmental structure, high drug loading, simple and convenient method of preparation, use of biodegradable lipids such as glycerol monooleate, encapsulation of hydrophilic, hydrophobic and amphiphilic moieties, targeted and controlled release make them versatile bioactive carriers that can be administered through multiple biological routes like topical, transdermal, parenteral, and oral. Cubosomes have appreciable applications in various fields especially in the pharmaceutical industry where they are used as potential bioactive carriers. Molecules like paclitaxel, oligonucleotide, δ-amino-levulinic acid, bovine serum albumin, etc. can be easily delivered through this system. This article provides a detailed note on the structure of cubosomes, ingredients and techniques used for their preparation, mechanism of drug release, applications and routes of drug administration, their formulations, patent review and market scenario.

Isolation and Molecular Identification of Biosurfactant Producing Soil Bacteria

Biosurfactants are amphiphilic compound, having hydrophilic and hydrophobic moieties enabling them to reduce surface and interfacial tension at the surface. Their unique properties are applied in various industries such as foaming and wetting agents, emulsifiers, detergents and bioremediation. A total of 98 isolates showed biosurfactant activity using hemolytic activity, drop collapse test and oil spreading assay. All isolates were rod-shaped, Gram positive and majority of them were non-endospore former. Only the isolates showing the highest percentage of emulsification index (E24) and ability to reduce tension were used for species identification using 16S rDNA gene sequencing which were isolates A1(6) and A2(1). Both isolates were identified as Bacillus sp. cp-h50 and Bacillus sp. XT-24 respectively, rod-shaped, endospore former and Gram positive. The biosurfactant produced by both species showed high emulsification index (E24) (A1(6), 63.3% and A2(1), 46.7%) and good surfactant capacity. The size of amplified gene of 16S rDNA gene was approximately 1.5 kb. These features provide evidence that both species could be a potential biosurfactant producer with proper optimization for the production of biosurfactant. The biosurfactant produced by both bacterial species were identified as surfactin using Fourier Transform Infrared Spectroscopy (FTIR).

Humic extracts of hydrochar and Amazonian Dark Earth: Molecular characteristics and effects on maize seed germination

Inspired by the presence of anthropogenic organic matter in highly fertile Amazonian Dark Earth (ADE), which is attributed to the transformation of organic matter over thousands of years, we explored hydrothermal carbonization as an alternative for humic-like substances (HLS) production. Hydrothermal carbonization of sugarcane industry byproducts (bagasse and vinasse) in the presence and absence of H3PO4 afforded HLS, which were isolated and compared with humic substances (HS) isolated from ADE in terms of molecular composition and maize seed germination activity. HLS isolated from sugarcane bagasse hydrochar produced in the presence or absence of H3PO4 comprised both hydrophobic and hydrophilic moieties, differing from other HLS mainly in terms of phenolic content, while HLS isolated from vinasse hydrochar featured hydrophobic structures mainly comprising aliphatic moieties. Compared to that of HLS, the structure of soil-derived HS reflected an increased contribution of fresh organic matter input and, hence, featured a higher content of O–alkyl moieties. HLS derived from lignocellulosic biomass were rich in phenolics and promoted maize seed germination more effectively than HLS comprising alkyl moieties. Thus, HLS isolated from bagasse hydrochar had the highest bioactivity, as the presence of amphiphilic moieties therein seemed to facilitate the release of bioactive molecules from supramolecular structures and stimulate seed germination. Based on the above results, the hydrothermal carbonization of lignocellulosic biomass was concluded to be a viable method of producing amphiphilic HLS for use as plant growth promoters.

Self-Assembly and Functions of Star-Shaped Oligomeric Surfactants.

Oligomeric surfactants consist of three or more amphiphilic moieties which are connected by spacer groups covalently at the level of headgroups. It provides a possible route to bridge the gap from conventional single-chain surfactants to polymeric surfactants and leads to many profound improvements in the properties of surfactants in aqueous solution and at the air/water and water/solid interfaces. Generally, oligomeric surfactants are categorized into linear, ring-like, and star-shaped on the basis of the topological structures of their spacer groups, and their aggregation behavior strongly depends on the resultant topological structures. In recent years, we studied trimeric, tetrameric, and hexameric surfactants with a star-shaped spacer which spreads from a central site of elemental nitrogen or carbon, and their charged headgroups connect with each other through the spacers. It has been found that both the nature of spacer groups and the degree of oligomerization show important influences on the self-assembly of oligomeric surfactants and provide great possibilities in fabricating various surfactant aggregate morphologies by adjusting the molecule conformations. The unique self-assembly behavior endows them with superior physicochemical properties and potential applications. This feature article summarizes the development of star-shaped oligomeric surfactants, including self-assembly at the air/water and water/solid interfaces, self-assembly in aqueous solution, and their functions. We expect that this review could provide a comprehensive understanding of the structure-property relationship and various potential applications of star-shaped oligomeric surfactants and offer additional motivation for their future research.

Microscopic Examination of Polymeric Monoguanidine, Hydrochloride-Induced Cell Membrane Damage in Multidrug-Resistant Pseudomonas aeruginosa.

Advances in antimicrobial activities of molecule-containing, multiple guanidinium groups against antibiotics-resistant bacteria should be noted. The synthesized polyoctamethylene monoguanidine hydrochloride (POGH), carrying cationic amphiphilic moieties, display excellent activity against multidrug-resistant Pseudomonas aeruginosa (MDR-PA) and other antibiotics-resistant bacteria. The membrane damage effects of POGH on MDR-PA were clarified using beta-lactamase activity assay, confocal fluorescence microscopy, scanning electron microscopy, and transmission electron microscopy. The results showed that POGH disrupted both the outer and inner membranes and the intracellular structure of MDR-PA to different extents depending on the dose. All concentrations of POGH within 3–23 μg/mL increased the outer membrane permeability, which facilitated the release of beta-lactamase across the inner membrane. A median dose (10 μg/mL) of POGH led to the separation of the inner and outer membrane, an increase in the membrane gap, and outer membrane structure damage with still maintained overall cytoskeletal structures. The application of a 30 μg/mL dose of POGH led to the collapse of the outer membrane, cellular wrinkling, and shrinkage, and the formation of local membrane holes. The disruption of the outer and inner membranes and the formation of the local membrane holes by a relative high dose were probably the main bactericidal mechanism of POGH. The microscopic evidence explained the strong outer-membrane permeation ability of guanidine-based antimicrobial polymers, which could be considered for the molecular design of novel guanidine-based polymers, as well as the damaged membrane structure and intracellular structure of MDR-PA.

Nano-structured gemini-based supramolecular solvent for the microextraction of cyhalothrin and fenvalerate.

A novel supramolecular solvent-based microextraction followed by high-performance liquid chromatography with ultraviolet detection method has been developed for the extraction and determination of two pyrethroid analytes, cyhalothrin and fenvalerate, in water and soil samples. The liquid-liquid-phase separation of surfactants has been used in analytical extraction. The surfactant-rich phase is a nano-structured liquid, recently named as a supramolecular solvent, generated from the amphiphiles. The alkyl carboxylic acid based supramolecular solvents were introduced before. Coacervates made up of gemini surfactant, consisting of two amphiphilic moieties, were first used as solvent. The effective parameters on extraction (i.e., type of organic solvent, the amount of surfactant and volume of tetrahydrofuran, sample solution pH, salt addition, ultrasonic and centrifugation time) were investigated and optimized. Under the optimum conditions, preconcentration factors of 110 and 145 were obtained for the analytes. The linearity was 0.5-200.0 μg/L with the correlation of determination of (R(2) ) ≥ 0.9984. The limit of detection of the method was (S/N = 3) 0.2μg/L, and precisions in the range of 6.3-10.3% (RSDs, n = 5) were obtained. This method has been successfully applied to analyze real samples, and good recoveries in the range of 101.2-108.8% were obtained.

Transitions in the Molecular Configuration and Aggregates for Mixtures of a Star-Shaped Hexameric Cationic Surfactant and a Monomeric Anionic Surfactant.

A hexameric cationic ammonium surfactant (PAHB), in which six amphiphilic moieties were connected by a star-shaped spacer group, adopted star-shaped, claw-like, and pyramid-like molecular configurations in aqueous solution, depending on the concentration. Herein, we studied the effect of adding sodium dodecyl sulfate (SDS) on the configuration and aggregation behavior of PAHB. Taking these three configurations of PAHB as initial states, the addition of SDS caused transitions of the star-shaped and claw-like configurations into a pyramid-like configuration, whilst the pyramid-like configuration remained unchanged. Moreover, the SDS/PAHB aggregates experienced transition from small spheres to large spherical fingerprint-like aggregates, no matter the initial state of PAHB. Molecular packing in the aggregates was also studied. These results have improved our understanding about the cooperative interactions between star-shaped oligomeric surfactants and monomeric surfactants, which should guide future applications of this unique type of surfactant.

Interfacial dilatational deformation accelerates particle formation in monoclonal antibody solutions.

Protein molecules are amphiphilic moieties that spontaneously adsorb at the air/solution (A/S) interface to lower the surface energy. Previous studies have shown that hydrodynamic disruptions to these A/S interfaces can result in the formation of protein aggregates that are of concern to the pharmaceutical industry. Interfacial hydrodynamic stresses encountered by protein therapeutic solutions under typical manufacturing, filling, and shipping conditions will impact protein stability, prompting a need to characterize the contribution of basic fluid kinematics to monoclonal antibody (mAb) destabilization. We demonstrate that dilatational surface deformations are more important to antibody stability when compared to constant-area shear of the A/S interface. We have constructed a dilatational interfacial rheometer that utilizes simultaneous pressure and bubble shape measurements to study the mechanical stability of mAbs under interfacial aging. It has a distinct advantage over methods utilizing the Young-Laplace equation, which incorrectly describes viscoelastic interfaces. We provide visual evidence of particle ejection from dilatated A/S interfaces and spectroscopic data of ejected mAb particles. These rheological studies frame a molecular understanding of the protein-protein interactions at the complex-fluid interface.

Dimerization of 30Kc19 protein in the presence of amphiphilic moiety and importance of Cys-57 during cell penetration.

Recently, the recombinant 30Kc19 protein, originating from silkworm hemolymph of Bombyx mori has attracted attention due to its cell-penetrating property and potential application as a protein delivery system. However, this observation of penetration across cell membrane has raised questions concerning the interaction of the protein-lipid bilayer. Here, we report a dimerization propensity of the 30Kc19 protein in the presence of amphiphilic moieties; sodium dodecyl sulfate (SDS) or phospholipid. Native PAGE showed that the 30Kc19 monomer formed a dimer when SDS or phospholipid was present. In the glutathione-S-transferase (GST) pull-down assay, supplementation of the 30Kc19 protein to mammalian cell culture medium showed dimerization and penetration; due to phospholipids at the cell membrane, the main components of the lipid bilayer. Mutagenesis was performed, and penetration was observed by 30Kc19 C76A and not 30Kc19 C57A, which meant that the presence of cysteine at position 57 (Cys-57) is involved in dimerization of the 30Kc19 at the cell membrane during penetration. We anticipate application of the native 30Kc19 protein with high cell-penetrating efficiency for delivery of cargos to various cell types. The intracellular cargo delivery using the 30Kc19 protein is a non-virus derived (e.g. TAT) delivery method, which can open up new approaches for the delivery of therapeutics in bioindustries, such as pharma- and cosmeceuticals.

Photodegradation of Chlorobenzenes in Micellar Aqueous Solutions of Gemini Surfactants

Photodegradation of 1,2,4-trichlorobenzene (1,2,4-TCB) was examined in one kind of Gemini surfactant solution (ethylene dioctadecyl dimethyl ammonium bromide) and two kinds of conventional surfactant solutions (sodium dodecyl sulfate and polyoxyethylene polyoxypropylene ether). Compared with conventional surfactants, Gemini surfactants make up of two identical or different amphiphilic moieties connected by a spacer group. Under UV irradiation at 254 nm, 1,2,4-trichlorobenzene was decomposed in the three micellar solutions, but the photodegradation rate of 1,2,4-trichlorobenzene in the Gemini surfactant solution was 3.54% and 11.81% higher than those in other two conventional surfactant solutions respectively. Thus, the photochemical reactions of chlorobenzenes can be enhanced in Gemini surfactant solutions.

Selective biodegradation of sorbitan ethoxylated surfactants by soil microorganisms

Surfactants have received increasing interest as potential agents for the enhanced remediation of soils and groundwater contaminated with polycyclic aromatic hydrocarbons (PAHs). However, the fate of surfactants with respect to biological transformations and associated changes in their characteristics has not been addressed clearly. Thus, the biodegradation of ethoxylated sorbitan fatty ester non-ionic surfactants, referred to as Tween surfactants, was investigated in this study. The PAH-degrading soil microbes partially utilized the surfactant as a carbon source (26.9–32.7% of initial dose). The characterization of biodegraded surfactants revealed that the partial biodegradation occurred selectively on the hydrophobes of surfactants, resulting in an imbalance of amphiphilic moieties of surfactants. Consequently, the critical micelle concentration values increased by 61.9–88.0% and the micellar solubilization ratio values decreased by 66.5–84.3% after the surfactant biodegradation. These observations supported our conclusion that the partial and selective microbial degradation of surfactants can result in a significant reduction of surface-active and micellar solubilization capacities of surfactants. The findings of this study are expected to provide important implications for the application of surfactant-mediated remediation processes for PAHs.

Controlling the self-assembly of cationic bolaamphiphiles: counterion-directed transitions from 0D/1D to exclusively 2D planar structures

Self-assembly of cationic bolaamphiphiles is usually reported to form one-dimensional (1D) or zero-dimensional (0D), rather than two-dimensional (2D) structures. Here we have found a facile counterion-directed structure switch for such amphiphilic moieties. 0D/1D structures formed by self-assembly of cationic bolaamphiphiles can be converted into 2D planar structures by a simple counterion change to tosylate. As indicated by the single crystal structure and variable-temperature NMR studies, the strong binding between tosylate counterions and cationic headgroups drives the formation of 2D planar structures. It is highly anticipated that this approach may present as a simple methodology to control the stacking of the embedded conjugated cores in bolaamphiphiles, therefore modulating optoelectronic properties and function in such assemblies.

Perfluorinated lipids for drug delivery

SYNTHESIS AND FORMULATION HYPOTHESIS Perfluorocarbons (PFCs) are widely used as blood substitutes, MRI (magnetic resonance imaging) tracers, and ultrasound agents.1,2 The unique physicochemical properties of PFCs, such as high biological and chemical inertness, low cohesiveness and surface tension, lipophobicity and hydrophobicity, are advantageous for the design of reagents for both drug delivery and imaging. Self-assembled structures such as micelles formed from perfluorinated amphiphilic moieties have been reported as potential drug carriers.3 Incorporation of perfluorinated compounds into colloidal systems like vesicles, liposomes and nanoemulsions (NEs) alters the drug release.4,5 Also, incorporation of inert PFCs provides added stability to the drug in vivo.4 Hence incorporation of PFCs into colloids would yield a unique system with properties that can be exploited to modulate the drug loading and release.