Cationic Micelles Research Articles

Cationic Micelles Outperform Linear Polymers for Delivery of Antisense Oligonucleotides in Serum: An Exploration of Polymer Architecture, Cationic Moieties, and Cell Addition Order.

Antisense oligonucleotides (ASOs) are an important emerging therapeutic; however, they struggle to enter cells without a delivery vehicle, such as a cationic polymer. To understand the role of polymer architecture for ASO delivery, five linear polymers and five diblock polymers (capable of self-assembly into micelles) were synthesized with varying cationic groups. After complexation of each polymer/micelle with ASO, it was found that less bulky cationic moieties transfected the ASO more effectively. Interestingly, however the ASO internalization trend was the opposite of the transfection trend for cationic moiety, indicating internalization is not the major factor in determining transfection efficiency for this series. Micelleplexes (micelle-ASO complexes) generally enable higher transfection efficacy as compared to polyplexes (linear polymer-ASO complexes). Additionally, the order of addition of cells and complexes was explored. Linear polyplexes showed better transfection efficiency in adhered cells, whereas micelleplexes delivered the ASO more efficiently when the cells and micelleplexes were added simultaneously. This phenomenon may be due to increased cell-complex interactions as micelleplexes have increased colloidal stability compared to polyplexes. These findings emphasize the importance of polymer composition and architecture in governing the cellular interactions necessary for transfection, thus allowing advancement in the design principles for nonviral nucleic acid delivery formulations.

Effects of cationic and anionic micelles on the redox reaction of Erythrosine B by H2O2 in presence of Cu‐Fe nanoparticles

AbstractKinetic investigation of the degradation of Erythrosine B (EB) by H2O2 and copper‐iron bimetallic nanoparticles was carried out spectrophotometrically. The degradation was carried out under the condition of sonication at 40°C. The co‐precipitation method was used for the fabrication of CuO/Fe2O3 (Cu‐Fe) in an alkaline solution and characterized by SEM, XRD, FTIR, TEM, EDS, and BET methods. In the absence of the Cu‐Fe, no degradation of EB by H2O2 was observed. The presence of Cu‐Fe resulted into the degradation of EB by H2O2. The kinetics of the degradation was studied under the conditions of variation of the amount of nanoparticles and at different concentrations of EB, H2O2, H+, surfactants (sodium dodecyl sulphate; SDS and cetyltrimethylammonium bromide; CTABr). The rate of reaction depends on the amount of Cu‐Fe and [H2O2]. The rate constant values gave the peaked like curve (with maximum value at pH 3) at different pH. The dye degradation decreased with the increase in presence of (SDS) and (CTABr).

Aggregates of cationic calix[4]arenes in aqueous solution as media for governing protolytic equilibrium, fluorescence, and kinetics

Many water-soluble ionic calixarenes readily form micelle-like aggregates in aqueous solution. Presently, it is firmly proved that such aggregates tend to shift the state of the acid-base equilibrium of indicator dyes just in the same manner as cationic surfactant micelles do. In this paper, we further the corresponding studies and report the peculiarities of several kinds of solvatochromic effects, fluorescence, acid-base equilibrium and kinetic processes in aqueous solutions of four cationic amphiphilic calix[4]arenes bearing hydrophilic choline groups at the upper rim: 5,11,17,23-tetra(N,N-dimethyl-N-hydroxyethylammonium)methylene-25,26,27,28-tetraalkyl-oxycalix[4]arene tetrachlorides. n-Propyl, n-hexyl, n-octyl, and n-dodecyl were used as alkyls, and the calixarenes were designated as of Cn-C4A-Ch, where n = 3, 6, 8, and 12, respectively. The principal colloidal properties, i.e., particle size and electrophoretic mobility of aggregates were characterized via dynamic light scattering. In parallel, the results were compared with those obtained in the presence of micelles of the common cationic surfactant cetyltrimethylammonium bromide and of large-sized aggregates of the calix[6]arene with six methoxy groups at the lower rim. As tools, molecular probes of triphenylmethine and fluorescein series, as well as the solvatochromic Reichardt’s dye were used. The obtained block of data sheds light upon the properties of calixarene aggregates as tools for governing chemical processes.

Solubilization of pyrene by mixed polymer-cationic/nonionic surfactant systems: Effect of polymer concentration

Polymers can be used to alter the ability of surfactant micelles to solubilize PAHs depending upon polymer–surfactant interactions. The focus of this study is to investigate the solubilization ability of the mixtures of anionic polymer sodium carboxymethyl cellulose (NaCMC) with nonionic polyoxyethylene [10] cetyl ether (Brij 56) and cationic cetyltrimethylammonium bromide (CTAB) surfactant micelles towards pyrene (PAH). Solubilization efficiency of these mixed systems and their comparison with individual systems has been quantified in terms of the molar solubilization ratio, micelle - water partition coefficient and free energy of solubilization. While the addition of anionic polymer NaCMC accelerates the solubilization capacity of cationic CTAB micelles, that of nonionic Brij56 micelles was retarded. Moreover, enhancement in the solubilization capacity of the above said mixed systems is observed as the polymer concentration changes from below overlap (i.e.; 0.5 %) to overlap (i.e.; %).

Inhibition of Mitochondrial Biosynthesis Using a "Right-Side-Out" Membrane-Camouflaged Micelle to Facilitate the Therapeutic Effects of Shikonin on Triple-Negative Breast Cancer.

The mitochondria represent a potential target for the treatment of triple-negative breast cancer (TNBC) and shikonin (SK) has shown remarkable therapeutic effects on TNBC. Herein, it is found that SK possesses potent inhibitory effects on mitochondrial biogenesis via targeting polymerase gamma (POLG). However, its application is restricted by its poor aqueous solubility and stability, and therefore, a biomimetic micelle to aid with tumor lesion accumulation and mitochondria-targeted delivery of SK is designed. A folic acid (FA) conjugated polyethylene glycol derivative (FA-PEG-FA) is inserted onto the external membranes of red blood cells (FP-RBCm) to prepare a "right-side-out" RBCm-camouflaged cationic micelle (ThTM/SK@FP-RBCm). Both FP-RBCm coating and a triphenylphosphine (TPP) moiety on the periphery of micelles contribute to tumor lesion distribution, receptor-mediated cellular uptake, and electrostatic attraction-dependent mitochondrial targeting, thereby maximizing inhibitory effects on mitochondrial biosynthesis in TNBC cells. Intravenous administration of ThTM/SK@FP-RBCm leads to profound inhibition of tumor growth and lung metastasis in a TNBC mouse model with no obvious toxicity. This work highlights the mitochondria-targeted delivery of SK using a "right-side-out" membrane-camouflaged micelle for the inhibition of mitochondrial biogenesis and enhanced therapeutic effects on TNBC.

Solubilization of caffeic acid into the cationic micelles and biogenic synthesis of silver nanoparticles for the degradation of dye

Solubilization of caffeic acid into the aqueous solution of cationic cetyltrimethlyammonium bromide (CTAB) has been studied by using differential spectroscopic and conductivity methods. The solubility of caffeic acid increases with increasing the CTAB concentrations. The solubilization constant of caffeic acid into CTAB (KX = 1.8 × 105), standard free energy (ΔG0P = −30.0 kJ/mol), and relative solubility (St/S0 = 53.5) were estimated at room temperature from UV–visible data. The critical micellar concentration (CMC) of CTAB decreases linearly with caffeic acid concentration due to the presence of hydrophobic benzene moiety. The interaction of caffeic acid with CTAB has also been discussed. The solubilized caffeic acid was used as a reducing agent for the preparation of silver nanoparticles (AgNPs). The as-prepared AgNPs were used as an activator of persulphate. The generated reactive oxygen species (OH•) and reactive sulphur species SO4-•) were responsible for the degradation of xylenol orange dye in water.

Facile Construction of a Two-in-One Injectable Micelleplex-Loaded Thermogel System for the Prolonged Delivery of Plasmid DNA

Nanoparticle-hydrogel systems have recently emerged as a class of interesting hybrid materials with immense potential for several biomedical applications. Remarkably, the incorporation of nanoparticles into a hydrogel may yield synergistic benefits lacking in a singular system. However, most synthetic strategies require laborious steps to achieve the system, severely restricting the process of translational research. Herein, a facile strategy to access a two-in-one system comprising two distinct polyurethane (PU)-based micellar systems is demonstrated and applied as a novel sustained gene delivery platform, where the two PUs are synthesized similarly but with slightly different compositions. One PU forms cationic micelles that complex with plasmid DNA (pDNA), which are loaded into a thermogel formed by another PU micellar system for the prolonged release of pDNA micelleplexes. Specifically, a thermogelling multiblock PU copolymer (denoted as EPH) was synthesized via the step-growth polymerization of poly(ethylene glycol), poly(propylene glycol), and poly(3-hydroxybutyrate). By further introducing a cationic extender, 3-(dimethylamino)-1,2-propanediol, into the reaction feed, a series of cationic PUs (denoted as EPHD) with varying compositions were obtained. The EPHDs formed positively charged micelles in aqueous solutions, efficiently condensed pDNA into nano-sized micelleplexes (<200 nm) at optimized w/w ratios, and mediated transient green fluorescence protein expression in HEK293T cells at 48 h post-transfection. On the other hand, aqueous EPH solution (4 wt %) was injectable at 4 °C and rapidly gelled upon heating to 37 °C to form a stable hydrogel depot. EPHD/pDNA micelleplexes were easily loaded into EPH by mixing the solutions at 4 °C, before heating to 37 °C, leading to the resultant hydrogel system. The in vitro release study revealed that while free pDNA loaded in the thermogel was completely released in 2 weeks, the release of EPHD/pDNA micelleplexes was prolonged to at least 28 days, suggesting substantial micelleplex-hydrogel interactions. Intact, bioactive, and noncytotoxic EPHD/pDNA micelleplexes in the release media were proved by gel retardation, in vitro gene transfection, and CCK-8 cytotoxicity assay results, respectively. Collectively, this work presents a simple approach to achieving and optimizing a novel two-in-one nanoparticle-hydrogel system for the prolonged delivery of pDNA and may be promising for long-term gene delivery applications.

Polycation Architecture Affects Complexation and Delivery of Short Antisense Oligonucleotides: Micelleplexes Outperform Polyplexes.

Herein, we examine the complexation and biological delivery of a short single-stranded antisense oligonucleotide (ASO) payload with four polymer derivatives that form two architectural variants (polyplexes and micelleplexes): a homopolymer poly(2-dimethylaminoethyl methacrylate) (D), a diblock polymer poly(ethylene glycol)methylether methacrylate-block-poly(2-dimethylaminoethyl methacrylate) (ObD), and two micelle-forming variants, poly(2-dimethylaminoethyl methacrylate)-block-poly(n-butyl methacrylate) (DB) and poly(ethylene glycol)methylether methacrylate-block-poly(2-dimethylaminoethyl methacrylate)-block-poly(n-butyl methacrylate) (ObDB). Both polyplexes and micelleplexes complexed ASOs, and the incorporation of an Ob brush enhances colloidal stability. Micellplexes are templated by the size and shape of the unloaded micelle and that micelle-ASO complexation is not sensitive to formulation/mixing order, allowing ease, versatility, and reproducibility in packaging short oligonucleotides. The DB micelleplexes promoted the largest gene silencing, internalization, and tolerable toxicity while the ObDB micelleplexes displayed enhanced colloidal stability and highly efficient payload trafficking despite having lower cellular uptake. Overall, this work demonstrates that cationic micelles are superior delivery vehicles for ASOs denoting the importance of vehicle architecture in biological performance.

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy.

PurposeOral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with more than 300,000 new cases annually. Despite advances in existing treatments, including surgery, radiation, chemotherapy, and immunotherapy, the overall survival and prognosis have remained poor. However, gene therapy based on non-viral vectors provides new ideas for the treatment of OSCC. Here, we aimed to prepare and describe the synthesis, biosafety, and preclinical efficacy of DOTAP-mPEG-PCL (DMP) in OSCC gene therapy.MethodsWe prepared a nano-sized hybrid cationic micelle DMP. DMP micelles were prepared by self-assembling cationic lipid DOTAP and mPEG-PCL polymer. We evaluated the characteristics of this cationic micelle in vitro. Combined with encoding the apoptosis-inducing BimS gene, we established the DMP/phBimS complex and evaluated its anti-tumor effect in vitro. We also established a mouse tongue xenograft model to evaluate the antitumor effect of the DMP/phBimS complex in vivo through local and systemic administration prospectively.ResultsThe DMP cationic micelle is spherical in shape, with an average diameter of 28.32 ± 3.56 nm and an average zeta potential of 43.43 ± 0.82 mV. By activation of lipid raft-mediated endocytosis caveolin-mediated endocytosis, DMP could efficiently deliver plasmid into SCC15 cells (efficiency: 52.07% ± 1.63%), with an ideal biosecurity. When loaded by plasmid encoding the apoptosis-inducing BimS gene, the DMP/phBimS complex exhibited an obvious anti-proliferation effect of SCC15 in vitro through the apoptosis pathway (33.9% ± 2.62% apoptosis rate). By local administration, the DMP/phBimS complex showed ideal anti-tumor properties in the nude mouse tongue xenograft model, with an average tumor inhibition rate of 65.66%. Furthermore, through systematic administration, the DMP/phBimS complex obviously inhibited OSCC growth, with an average inhibition rate of 45.63% (DMP/phBimS) and an appropriate biocompatibility.ConclusionThe DMP/phBimS complex is an optional effective option for suicide gene therapy for OSCC.

The Catalytic Influence of Polymers and Surfactants on the Rate Constants of Reaction of Maltose with Cerium (IV) in Acidic Aqueous Medium

Kinetics of the reaction of maltose with cerium ammonium sulfate were analyzed spectrophotometrically by observing the decrease of the absorbance of cerium (IV) at 385 nm in the presence and absence of polyethylene glycols (600, 1500, and 4000) and polyvinylpyrrolidone (PVP), in addition to anionic micelles of sodium dodecyl sulfate (SDS), cationic micelles of cetyltrimethylammonium bromide (CTAB) and non-ionic micelles of Tween 20 surfactants. Generally, there is little literature about using the polymers (PEGs and PVP) as catalysts in the oxidation-reduction reactions. Therefore, the major target of this work was to investigate the influence of the nature of polymers and surfactants on the oxidation rates of maltose by cerium (IV) in acidic aqueous media, as well as employing the Piszkiewicz model to explain the catalytic effect. The kinetic runs were derived by adaptation of the pseudo first-order reaction conditions with respect to the cerium (IV). The reaction was found to be first-order with respect to the oxidant and fractional-order to maltose and H2SO4. The reaction rates were enhanced in the presence of polymer and micellar catalysis. Indeed, the surfactants were found to work perfectly close to their critical micelle concentrations (CMC). Electrostatic interaction and H-bonding appear to play an influential role in binding maltose molecules to polymer/surfactant micelles, while oxidant ions remain at the periphery of the Stern layer within the micelle.

Direct synthesis of Poly(Ԑ-Caprolactone)-block-poly (glycidyl methacrylate) copolymer and its usage as a potential nano micelles carrier for hydrophobic drugs

Ring-opening (ROP) and enzymatic copolymerization (ECP) are among the most widely used approaches for synthesizing copolymers of polycaprolactone (PCL). It involves multiple-step reactions and the utilization of enzymes that make the process a lot more complicated, time consuming, and expensive. Atom transfer radical polymerization (ATRP) has been adopted to synthesize a novel amphiphilic copolymer in our study. The study presents a method to eliminate the ROP/ECP multiple steps in monomer polymerization thus making the process simpler and smoother. The synthesis of cationic polymer micelles copolymer of PCL-PGMA (polycaprolactone grafted poly glycidyl methacrylate) was carried out using direct functionalization of hydroxy group in crude PCL to achieve a higher degree of functionalization, i.e., 12.8% for macroinitiator. FTIR and 1H-NMR confirmed the successful synthesis of the copolymer with better control over the molecular weight with a PDI (1.84). DSC and XRD results showed the reduction of crystallinity by 86.81%, making copolymer more compatible for drug delivery application. The synthesized copolymer was further converted to nano-micelles drug carrier having an average size of 96.08 ± 21.22 nm. The drug encapsulation efficiency achieved was 60.0 ± 1.7%, and nano-micelles rendered a slow and controlled release of naproxen with long-term storage stability.

Effect of drug aceclofenac on physicochemical properties of mixed micellar systems

In this article, the effect of the drug aceclofenac (ACF) on the properties of three mixed micellar systems are studied. The three systems were pluronic L64 + F127 (nonionic-nonionic), pluronic L64 + CTAB (cetyltrimethyl ammonium bromide), (nonionic-cationic) and L64 + SDS (Sodium dodecyl sulphate), (nonionic-anionic) combinations. The physicochemical parameters were characterized by different techniques such as UV visible spectroscopy, FTIR, conductance, DLS, and SEM. The presence of ACF affected the nonionic-ionic mixed micelles more than the nonionic-nonionic group as evidenced by UV spectroscopy. From the DLS measurement, it was observed that ACF enhanced the size of the single micelle of pluronic L64 from 98 to 168 nm. The size of the cationic mixed micelle with ACF displayed 329 nm and the anionic mixed one showed 291 nm suggesting enhanced entrapment efficiency of their mixed micelle compared to the single micelles. The size was also reconfirmed by SEM analysis. From the conductivity measurements of the two nonionic-ionic micellar systems, the counter ion binding constant β, and the thermodynamic parameters ΔG, ΔH, and ΔS were determined. The negative value of ΔG infers spontaneous binding between ACF and ionic mixed micelles.Article highlightsIonic mixed micelles are more effective than nonionic pair.ACF has more spontaneous binding with anionic mixed micelle compared to cationic.The drug entrapment efficiency is better in mixed micelles than in single micelles.

Hyaluronan interactions with cationic surfactants – Insights from fluorescence resonance energy transfer and anisotropy techniques

Interactions of hyaluronan with micelles formed by cationic surfactants were studied by the time-resolved measurement of fluorescence resonance energy transfer (FRET) using perylene and fluorescein as probes. Two surfactants were studied – Cetyltrimethylammonium bromide (CTAB) and Septonex. In pure micellar solutions, the same values of FRET efficiency were found for both surfactants, but values for the binding of the probe pair were lower for Septonex micelles than in the case of CTAB. This was attributed to steric effects of the carbethoxy group in the Septonex polar head. Upon the addition of hyaluronan, decreased FRET efficiency and increased binding were detected in comparison with pure surfactants. To resolve the structure of the formed aggregates, steady state and time-resolved fluorescence anisotropy was employed as an additional technique. All results indicated that cationic micelles bind to hyaluronan forming a pearl necklace structure with micelles of smaller size compared to pure surfactant. Besides theoretical interest, the studied polyelectrolyte-surfactant system may be interesting for the formulation of drug delivery systems.

Co‐delivery of paclitaxel and CXCL1 shRNA via cationic polymeric micelles for synergistic therapy against ovarian cancer

AbstractThe preparation of polymer therapeutics capable of synergistic co‐delivery systems for chemotherapeutic drugs and genes remains a tough problem in cancer therapy. Herein, we develop a novel co‐delivery system for chemotherapeutic drugs and genes. Paclitaxel (PTX) was covalently grafted onto the cationic copolymer poly(ethylene glycol)‐b‐poly(l‐lysine) (PEG‐b‐PLL) via a disulfide bond, and then CXCL1 shRNA was loaded on the cationic micelles PEG‐b‐PLL‐SS‐PTX by electrostatic interaction to construct PEG‐b‐PLL‐SS‐PTX/pDNA complex. The chemical structure of the complex was confirmed by gel permeation chromatography, 1H NMR and Fourier transform infrared spectroscopy. The binding ability of the cationic micelles and pDNA was detected by gel retardation assay. In vitro gene transfection studies revealed an enhanced gene transfection efficiency due to the co‐delivery of PTX and pDNA to ovarian cancer cells. In vitro and in vivo data demonstrated that the co‐delivery complex exhibited a synergistic role of chemotherapy and gene therapy and possessed enhanced antitumor effects. The strategy of using drug‐loaded cationic micelles as gene delivery carriers is a versatile approach to construct a co‐delivery system, which might result in more efficient cancer therapy. © 2022 Society of Industrial Chemistry.

Highly stretchable, elastic, antimicrobial conductive hydrogels with environment-adaptive adhesive property for health monitoring

HypothesisDevelopment of soft conductive materials has enabled the promising future of wearable electronics for motion sensing. However, conventional soft conductive materials typically lack robust adhesive and on-demand removable properties for a target substrate. Therefore, it is believed that the integration of superior mechanical properties, electrical conductivity, and tunable adhesive properties into hydrogels would support and improve their reliable sensing performance. ExperimentsA hydrogel ionic conductor composed of cationic micelles crosslinked in the polyacrylamide (PAM) network was designed and fabricated. The viscoelastic, mechanical, adhesion, electrical, and antimicrobial properties of the hydrogel were systematically characterized. FindingsThe developed ionic conductor possesses a range of desirable properties including mechanical performances such as excellent stretchability (>1100%), toughness, elasticity (recovery from 1000% strain), conductivity (2.72 S·m−1), and antimicrobial property, owing to the multiple non-covalent supramolecular interactions (e.g., hydrogen bonding, hydrophobic, and π-π/cation-π interactions) present in the cross-linked network. Meanwhile, the developed hydrogel is incorporated with different stimuli-responsive polymers and exhibits a tunable adhesive property (triggerable attachment and on-demand removable capabilities) in adapt to the surrounding environmental conditions (i.e., pH, temperature). With all these significant features, the resulting hydrogel ionic conductor serves as a proof-of-concept motion-sensing system with excellent sensitivity and enhanced reliability for the detection of a wide range of motions.

Anti-Oxidative and Anti-Inflammatory Micelles: Break the Dry Eye Vicious Cycle.

Dry eye disease (DED) impacts ≈30% of the world's population and causes serious ocular discomfort and even visual impairment. Inflammation is one core cause of the DED vicious cycle, a multifactorial deterioration in DED process. However, there are also reactive oxygen species (ROS) regulating inflammation and other points in the cycle from the upstream, leading to treatment failure of current therapies merely targeting inflammation. Accordingly, the authors develop micelle‐based eye drops (more specifically p38 mitogen‐activated protein kinases (MAPK) inhibitor Losmapimod (Los)‐loaded and ROS scavenger Tempo (Tem)‐conjugated cationic polypeptide micelles, designated as MTem/Los) for safe and efficient DED management. Cationic MTem/Los improve ocular retention of conjugated water‐soluble Tem and loaded water‐insoluble Los via electrostatic interaction with negatively charged mucin on the cornea, enabling an increase in therapeutic efficiency and a decrease in dosing frequency. Mechanistically, MTem/Los effectively decrease ROS over‐production, reduce the expression of proinflammatory cytokines and chemokines, restrain macrophage proinflammatory phenotypic transformation, and inhibit cell apoptosis. Therapeutically, the dual‐functional MTem/Los suppress the inflammatory response, reverse corneal epithelial defect, save goblet cell dysfunction, and recover tear secretion, thus breaking the vicious cycle and alleviating the DED. Moreover, MTem/Los exhibit excellent biocompatibility and tolerability for potential application as a simple and rapid treatment of oxidative stress‐ and inflammation‐induced disorders, including DED.

Cation Bulk and pKa Modulate Diblock Polymer Micelle Binding to pDNA.

Polymer-based gene delivery relies on the binding, protection, and final release of nucleic acid cargo using polycations. Engineering polymeric vectors, by exploring novel topologies and cationic moieties, is a promising avenue to improve their performance, which hinges on the development of simple synthetic methods that allow facile preparation. In this work, we focus on cationic micelles formed from block polymers, which are examined as promising gene compaction agents and carriers. In this study, we report the synthesis and assembly of six amphiphilic poly(n-butyl acrylate)-b-poly(cationic acrylamide) diblock polymers with different types of cationic groups ((dialkyl)amine, morpholine, or imidazole) in their hydrophilic corona. The polycations were obtained through the parallel postpolymerization modification of a poly(n-butyl acrylate)-b-poly(pentafluorophenyl acrylate) reactive scaffold, which granted diblock polymers with equivalent degrees of polymerization and subsequent quantitative functionalization with cations of different pKa. Ultrasound-assisted direct dissolution of the polycations in different aqueous buffers (pH = 1-7) afforded micellar structures with low size dispersities and hydrodynamic radii below 100 nm. The formation and properties of micelle-DNA complexes ("micelleplexes") were explored via DLS, zeta potential, and dye-exclusion assays revealing that binding is influenced by the cation type present in the micelle corona where bulkiness and pKa are the drivers of micelleplex formation. Combining parallel synthesis strategies with simple direct dissolution formulation opens opportunities to optimize and expand the range of micelle delivery vehicles available by facile tuning of the composition of the cationic micelle corona.

Quaternized Polysaccharide‐Based Cationic Micelles as a Macromolecular Approach to Eradicate Multidrug‐Resistant Bacterial Infections while Mitigating Antimicrobial Resistance (Small 12/2022)

Antibiotic Resistance In article number 2104885, Runhui Liu, Wei Jiang, Jie Cai, and co-workers construct quaternized polysaccharide-based cationic micelles with outstanding biocompatibility, excellent broad-spectrum antimicrobial ability and low propensity for resistance, effective inhibition and eradication of mature bacterial biofilms, and that accelerate MRSA-infected biofilms wound healing, which provides a new strategy to combat the global health crisis of antibiotic resistance.

PHOTOPHYSICAL ASPECTS OF POLARITY SENSITIVE FLUOROPHORE IN CATIONIC REVERSE MICELLES

In recent years, the field of reverse micelles has witnessed a significant growth of interest, partly due to the finding that proteins, other biopolymers, and even bacterial cells can be solubilized in the reverse micellar systems. Among surfactants capable of forming water in oil microemulsion, the cationic surfactant cetyltrimethylammonium bromide (CTAB) has received particular attention because of its ability to solubilize relatively large amount of water in a variety of hydrophobic organic solvents. Due to versatile photochemical and photophysical properties of Ru(II) complexes, Ru(II)- phenanthroline and its derivatives were used in this present work to form CTAB cationic reverse micelles and studied to characterise their photophysical properties such as absorption, emission and excited state life time. The findings from the spectral data observed in the present study proves that the excited state properties of Ru(II)-phenanthroline complexes are dramatically altered in the presence of reverse micelle. Specifically reverse micelle encapsulation of [Ru(dpphen)3]2+ complex in restricted environment causes blue shift in the emission maximum as well as have longer radiative lifetime. The blue shift in the emission maximum in the case of [Ru(dpphen)3]2+ indicates that the probes are near the water in oil reverse micellar interface, tightly bound and are not displaced towards the water pool of the micelle even at the highest water loading W0=50, which reveals the increased hydrophobicity. This highest fluorescence lifetime can serve as an excellent indicator to point out the location of the probe in a microheterogeneous system/environment.

Quaternized Polysaccharide-Based Cationic Micelles as a Macromolecular Approach to Eradicate Multidrug-Resistant Bacterial Infections while Mitigating Antimicrobial Resistance.

Microbial infections and microbial resistance lead to a high demand for new antimicrobial agents. Quaternized polysaccharides are cationic antimicrobial candidates; however, the limitation of homogeneous synthesis solvents that affect the molecular structure and biological activities, as well as their drug resistance remains unclear. Therefore, the authors homogeneously synthesize a series of quaternized chitin (QC) and quaternized chitosan (QCS) derivatives via a green and effective KOH/urea system and investigate their structure-activity relationship and biological activity in vivo and in vitro. Their study reveals that a proper match of degree of quaternization (DQ) and degree of deacetylation (DD') of QC or QCS is key to balance antimicrobial property and cytotoxicity. They identify QCS-2 as the optimized antimicrobial agent with a DQ of 0.46 and DD' of 82%, which exhibits effective broad-spectrum antimicrobial properties, good hemocompatibility, excellent cytocompatibility, and effective inhibition of bacterial biofilm formation and eradication of mature bacterial biofilms. Moreover, QCS-2 exhibits a low propensity for development of drug resistance and significant anti-infective effects on MRSA in vivo comparable to that of vancomycin, avoiding excessive inflammation and promoting the formation of new blood vessels, hair follicles, and collagen deposition to thus expedite wound healing.