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In simulations, particles are traditionally treated as rigid platforms with variable sizes, shapes, and interaction parameters. While this representation is applicable for rigid core platforms, particles consisting of soft platforms (e.g., micelles, polymers, elastomers, and lipids) inevitably deform upon application of external stress. We introduce a generic model for flexible particles, which we refer to as MetaParticles (MPs). These particles have tunable properties, can respond to applied tension, and can deform. A MP is represented as a collection of Lennard-Jones beads interconnected by spring-like potentials. We model a series of MPs of variable sizes and symmetries, which we subject to external stress, followed by relaxation upon stress release. The positions and the orientations of the individual beads are propagated by Brownian dynamics. The simulations show that the mechanical properties of the MPs vary with size, bead arrangement, and area of applied stress, and share an elastomer-like response to applied stress. Furthermore, MPs deform following different mechanisms, i.e., small MPs change shape in one step, while larger ones follow a multi-step deformation pathway, with internal rearrangements of the beads. This model is the first step toward the development and understanding of particles with adaptable properties with applications in the biomedical field and in the design of bioinspired metamaterials. [ABSTRACT FROM AUTHOR]

We characterize the self-assembly and phase behavior of Janus rods over a broad range of temperatures and volume fractions, using Langevin dynamics simulations and free energy calculations. The Janus rods consist of a line of fused overlapping spheres that interact via a soft-core repulsive potential, with the addition of an attractive pseudo-square-well tail to a fraction of the spheres (the coverage) ranging from 5% to 100% of sites. Competition between the stability of liquid crystal phases originating from shape anisotropy and assembly driven by directional interactions gives rise to a rich polymorphism that depends on the coverage. At low densities near the Boyle temperature, we observe the formation of spherical and tubular micelles at low coverages, while at higher coverages, randomly oriented monolayers form as the attractive parts of the rods overlap. At higher densities, bilayer structures appear and merge to form smectic and crystalline lamellar phases. All these structures gradually become unstable as the temperature is increased until eventually regular nematic and smectic phases appear, consistent with the hard rod limit. Our results indicate that the intermediate regime where shape-entropic effects compete with anisotropic attractions provided by site specificity is rich in structural possibilities and should help guide the design of rod-like colloids for specific applications. [ABSTRACT FROM AUTHOR]

In this paper, the responses of assembled behaviors of block polyelectrolytes (PEs) to the strength of electrostatic interactions are studied through molecular dynamic simulations. The results show that the assembled structures closely depend on the electrostatic strength. It should be noted that PE coacervation can outweigh the nucleation of hydrophobic blocks and invert the micelle structures at strong electrostatic strengths, leading to the formation of inverted micelles of PE cores and hydrophobic coronas. In the poor solvent condition for neutral block, diverse anisotropic micelles are presented; candy-like conventional micelles of hydrophobic cores and PE patches coexist with inverted candy-like micelles of PE cores and hydrophobic patches and with Janus micelles of semi-neutral aggregate and semi-PE cluster in the presence of divalent and trivalent counterions. The formation of conventional or inverted micelle is largely determined by the type of micellar fusion, which results from the nucleation competition between electrostatic correlation and hydrophobic interaction. The merge of micelles mediated by hydrophobic attraction leads to conventional hydrophobic cores, and the fusion induced by electrostatic correlations results in PE cores micelles. At strong electrostatic strengths, the PE chains exhibit rich conformations at trivalent counterions, ranging from a fully collapsed state to a rod-like state, and parallel alignment of PE chains is found. [ABSTRACT FROM AUTHOR]

We conduct dissipative particle dynamics simulations of nonionic surfactant solutions to investigate the statistical properties of micellar recombination. We categorize the recombination events into self-recombination, where two micelles created by scission join together, and non-self-recombination. We find that these two recombination events exhibit distinct statistical properties. The probability density function of the recombination time for self-recombination follows a power law, and we show that the mean squared displacement of the surfactants determines the exponent of the power law. In contrast, the survival function for non-self-recombination is exponential, which is consistent with the mean-field model. For non-self-recombination, we evaluate the mean recombination time for various aggregation numbers, temperatures, and surfactant volume fractions. We find a scaling law describing the mean recombination time of the micelles at equilibrium. [ABSTRACT FROM AUTHOR]

[Display omitted] Hypothesis: Micelles formed by copolymers with mixed solvophobic blocks have attracted much attention lately. It is expected that changing the mixed blocks sequence can be used as a tool to influence the micellization behavior in a way that is not equivalent to simply varying the incompatibility parameter for pure diblock-copolymers. Simulations: By using coarse-grained simulations, the micellization behavior of copolymers with twelve types of solvophobic blocks, which differed in the fraction f as well as the sequence of solvophilic units in the solvophobic blocks, was studied. To enable quantitative comparison of systems with different f , an "effective" incompatibility parameter was introduced. Findings: The micelles size distributions and dynamics were found to be significantly dependent on both f and the fine details of the sequence. When the solvophobic block sequences were obtained statistically using a model of copolymerization, a strong influence of the reactivity ratios on the resulting micelles was found. Even a moderate tendency to form gradient-like sequences resulted in a noticeable increase in the micelles size. The dynamic properties of the micelles were studied by investigating the rate at which the chains escape from them. The addition of soluble units into the solvophobic block was shown to dramatically decrease the tendency to form kinetically frozen states; gradient-like sequences demonstrated more sluggish dynamics. The physical reasons for the observed peculiarities are discussed in detail. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease whose pathophysiology is closely related to inflammation-associated cells and the microenvironment of inflamed joints. This study aimed to develop dual-targeted, reactive oxygen species (ROS)/pH dual-responsive, size-shrinkable intelligent micelles targeting M1 macrophages and fibroblast-like synoviocytes (FLSs) to enhance drug efficacy and safety. These micelles were surface-modified with PEG5000 to prolong their circulation time in the bloodstream and hide the targeting molecules. The optimized particle size allowed the micelles to reside in inflamed joints through the extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS) effect. The high concentration of ROS in the inflamed joint caused the detachment of the hydration layer of PEG5000, which was then specifically recognized and internalized by M1 macrophages and FLSs via CD44 receptor-mediated endocytosis, ultimately allowing the release of the drug into the acidic environment of the inflamed cells. The in vivo and in vitro evaluation showed that micelles precisely targeted the inflammatory site, thus inhibiting the expression of pro-inflammatory cytokines, reversing the polarization of M1 macrophages, inhibiting the invasion and migration of proliferative FLSs, and, at the same time, regulating the seeds and soils of RA. This "three birds with one stone" approach targeted multiple aspects of RA, opening new horizons for comprehensive treatment of RA. [ABSTRACT FROM AUTHOR]

[Display omitted] Electrostatic-templated polymerization (ETP) is a recently developed strategy for robust fabrication of stable polyion complex (PIC) micelles with regulated size and morphology, yet the kinetics and mechanism about this one pot process remain elusive. In ETP method, ionic monomers are polymerized in the presence of an oppositely charged ionic-neutral diblock copolymer as template. We investigate the monomer conversion and electrostatic assembly as a function of time, under different polymerization conditions of ionic strength, pH, template/monomer molar ratio and the presence of a cross-linker. The template copolymer accelerates the monomer conversion and formation of PIC micelles dependent on ionic strength and pH. The process follows the "Pick-up" mechanism, where monomers first convert into oligomers which complex with template to induce further chain growth and electrostatic assembly. Introducing cross-linker hardly impacts the reaction kinetics and "Pick-up" route, while it creates PIC micelles containing cross-linked ionic network assembly with the template. Further removing the template by concentrated salt provides purified ionic nanogels. The disclosed findings not only provide a better understanding of the polymerization-assembly process, but also optimize the controls of electrostatic-templated polymerization for the rational design and fabrication of diverse PIC micelles and polyelectrolyte particles. [ABSTRACT FROM AUTHOR]

Docosahexaenoic acid (DHA; 22-carbon-6) is renowned for its diverse biological activities and essential role in human wellness. However, owing to its highly unsaturated structure, dietary DHA is susceptible to oxidation and degradation in the gastrointestinal tract. Proteins are considered ideal carriers for protecting sensitive bioactive compounds like DHA from environmental factors. In this study, we prepared self-assembled micelles of ovalbumin (Ova), myosin (Myo), 7S soy globulin (Ssg), and β-lactoglobulin (β-la) to encapsulate DHA, resulting in O(DHA), M(DHA), S(DHA), and β(DHA) micelles via the chymotrypsin hydrolysis. We evaluated the encapsulation effectiveness of these micelles by assessing their encapsulation efficiency, storage stability, and bioaccessibility of DHA. The results indicated that O(DHA), M(DHA), S(DHA), and β(DHA) formed uniform, monodisperse nanospheres, with an outer shell composed of hydrolyzed micelle material and an inner core of encapsulated DHA. The secondary structures of Ova, Myo, Ssg, and β-la micelles were altered during the micelle formation process. The encapsulation rates for DHA in Ova, Myo, and β-la micelles were all above 70%, with Ssg micelles achieving over 90%. The zeta potential values of O(DHA), M(DHA), S(DHA), and β(DHA) remained between 20 and 30 mV over 4 weeks of storage. The particle diameters of O(DHA), S(DHA), and β(DHA) remained relatively stable throughout the storage period, while the diameter of M(DHA) showed significant changes. Additionally, the bioaccessibilities of O(DHA), M(DHA), and β(DHA) were all above 50%, with S(DHA) reaching 71.36 ± 4.27%. The encapsulation of DHA in Ova, Myo, Ssg, and β-la micelles enhanced the retention of DHA in gastrointestinal fluid. Ova, Myo, Ssg, and β-la micelles significantly improved the efficiency of DHA transport across a Caco-2 cell monolayer. Micelles containing DHA were more effective than free DHA in reducing total cholesterol (TC) and alanine aminotransferase (ALT) levels, increasing the number of autophagosomes, and upregulating the mRNA expression levels of PPARα and CPT1A in HepG2 cells, thereby reducing lipid accumulation. These findings support the use of Ova, Myo, Ssg, and β-la micelles as effective carriers for DHA. [ABSTRACT FROM AUTHOR]

Photodynamic Therapy (PDT) is a promising paradigm for treating cancer, especially superficial cancers, including skin and oral cancers. However, the effectiveness of PDT is hindered by the hydrophobicity of photosensitizers. Here, chlorin e6 (Ce6), a hydrophobic photosensitizer, was loaded into pluronic F127 micelles to enhance solubility and improve tumor-specific targeting efficiency. The resulting Ce6@F127 Ms demonstrated a significant increase in solubility and singlet oxygen generation (SOG) efficiency in aqueous media compared to free Ce6. The confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed the enhanced internalization rate of Ce6@F127 Ms in murine melanoma cell lines (B16F10) and human oral carcinoma cell lines (FaDu). Upon laser irradiation (666 nm), the cellular phototoxicity of Ce6@F127 Ms against B16F10 and FaDu was approximately three times higher than the free Ce6 treatment. The in vivo therapeutic investigations conducted on a murine model of skin cancer demonstrated the ability of Ce6@F127 Ms, when combined with laser treatment, to penetrate solid tumors effectively, which resulted in a significant reduction in tumor volume compared to free Ce6. Further, the Ce6@F127 Ms demonstrated upregulation of TUNEL-positive cells, downregulation of proliferation markers in tumor tissues, and prevention of lung metastasis with insignificant levels of proliferating cells and collagenase, as validated through immunohistochemistry. Subsequent analysis of serum and blood components affirmed the safety and efficacy of Ce6@F127 Ms in mice. Consequently, the developed Ce6@F127 Ms exhibits significant potential for concurrently treating solid tumors and preventing metastasis. The photodynamic formulation holds great clinical translation potential for treating superficial tumors. [ABSTRACT FROM AUTHOR]

Purpose: The integration of nanotechnology into biomedical imaging has significantly advanced diagnostic and theranostic capabilities. However, nanoparticle detection in imaging relies on functionalization with appropriate probes. In this work, a new approach to visualize free‐label nanoparticles using MRI and MRS techniques is described, consisting of detecting by 1H CSI specific proton signals belonging to the components naturally present in most of the nanosystems used in preclinical and clinical research. Methods: Three different nanosystems, namely lipid‐based micelles, liposomes, and perfluorocarbon‐based nanoemulsions, were synthesized, characterized by high resolution NMR and then visualized by 1H CSI at 300 MHz. Subsequently the best 1H CSI performing system was administered to murine models of cancer to evaluate the possibility of tracking the nanosystem by looking at its proton associated signal. Furthermore, an in vitro comparison between 1H CSI and 19F MRI was carried out. Results: The study successfully demonstrates the feasibility of detecting nanoparticles using MRI/MRS without probe functionalization, employing 1H CSI. Among the nanosystems tested, the perfluorocarbon‐based nanoemulsion exhibited the highest SNR. Consequently, it was evaluated in vivo, where its detection was achievable within tumors and inflamed regions via 1H CSI, and in lymph nodes via PRESS. Conclusions: These findings present a promising avenue for nanoparticle imaging in biomedical applications, offering potential enhancements to diagnostic and theranostic procedures. This non‐invasive approach has the capacity to advance imaging techniques and expand the scope of nanoparticle‐based biomedical research. Further exploration is necessary to fully explore the implications and applications of this method. [ABSTRACT FROM AUTHOR]

[Display omitted] Multifunctional micelles that permit both diagnosis and treatment present enormous advantage and potential for precision medicine. However, the inherent complexities and structural instability of these systems often cause unsatisfactory targeting and therapeutic performances. Herein, by ingenious design of a 2,5-bis(2-thienyl)pyrrole (SNS) modifier to covalently link with AS1411 aptamer and lipid segment, a simple strategy is proposed for one-step enzymatic preparation of interlocked aptamer-micelle (IApM) under bio-friendly conditions. The interlocked poly(SNS) skeleton in IApM can not only stabilize the micelle structure but also enhance near-infrared (NIR) absorption ability, thus further enhancing cellular internalization and photothermal therapy. In addition, the multivalent AS1411 aptamers tethered in the hydrophilic shell can simultaneously increase the specific binding affinity of DNA micelles and induce nucleus-targeted accumulation for DNA damage-triggered apoptosis. This DNA micelle achieves "best of both worlds" with enhanced biostability for cellular internalization and improved NIR photothermal conversion efficiency for nucleus-targeted therapy, which provides a promising formulation strategy for precision cancer treatment. [ABSTRACT FROM AUTHOR]

The growing number of viral infections and viral strains from year to year requires the creation of new, more effective antiviral drugs. One of the cost-effective ways to increase drug efficiency is the development of delivery systems for already known and clinically used drugs in order to overcome the challenges currently limiting their efficiency. This review presents the current status of silicon-based particles in this area. Silicon-based materials consist mainly of silicon and its compounds and can contain other inorganic oxides, i.e. are inorganic in nature. Their inorganic nature provides a number of advantages over organic materials (e.g. polymers, lipids, micelles, etc.) which are widely proposed and already used for the indicated purpose. This review provides information about the structural features of the silicon-based materials, methods of their preparation. It contains studies showing why and how the particles themselves can serve as antiviral agents or, as carriers, can help overcome the disadvantages of active drugs and increase their antiviral efficacy. The review highlights the enormous potential of silicon-based inorganic particles (pristine or modified with various inorganic and organic species) in the fight against widespread viral infections. [ABSTRACT FROM AUTHOR]

Tumor hypoxia is one of key challenges in deep tumor photodynamic therapy (PDT), and how to fix this issue is attracting ongoing concerns worldwide. This work demonstrates dually fluorinated unimolecular micelles with desirable and stable oxygen-carrying capacity, high cellular penetration, and integrative type I & II PDT for deep hypoxic tumors. Dually fluorinated star copolymers with fluorinated phthalocyanines as the core are prepared through photoinitiated electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization under irradiation with NIR LED light at room temperature, followed by assembly into unimolecular micelles. Perfluorocarbons (PFCs) are also introduced into the star polymers during the polymerization to further enhance and stabilize oxygen-carrying capacity, which is slightly affected by concentration-induced size transformation. PFCs assist unimolecular micelles with repelling mucin adsorption, which results in superior cellular uptake within 1 h and high effective accumulation rates in tumors of CT26 tumor-bearing mice within 24 h after systemic administration, and showing effective anti-tumor effects under the irradiation of NIR LED light. This work provides a new type of nano-photosensitizers for highly efficient hypoxic PDT. One of the major challenges in improving the efficiency of photodynamic therapy (PDT) for deep tumors is how to address tumor hypoxia, which is receiving continued attention worldwide. However, most of the reported oxygen carriers combine with photosensitizers by physical means and the carriers have the risk of dissociating easily, which is not conducive to long-term and efficient PDT, resulting in poor therapeutic effect. This work demonstrates dually fluorinated unimolecular micelles with desirable and stable oxygen-carrying capacity, high cellular penetration, and integrative type I & II PDT for enhanced deep hypoxic tumors, overcoming the key challenges of tumor hypoxia and low photosensitizer efficiency. [Display omitted] [ABSTRACT FROM AUTHOR]

The low penetration of antibacterial materials within biofilms results in a 1000‐fold decrease in bactericidal efficiency, complicating the complete removal of biofilms and potentially leading to persistent and recurrent bacterial infections that significantly impact human health. In this study, we present a multifunctional pH‐responsive antibacterial material based on random copolymers poly(dimethylaminoethyl methacrylate decyl ammonium bromide‐co‐polyethylene glycol methacrylate) copolymer (PQACs10‐co‐PEGMA10). The PQACs10‐co‐PEGMA10 copolymers could self‐assemble into micelles in selective solvent water. With the stealth function of polyethylene glycol (PEG), the PQACs10‐co‐PEGMA10 micelles can rapidly penetrate biofilms in a physiological environment and exhibit excellent antibacterial activity by exposing the quaternary ammonium salt (QACs) in an acidic microenvironment to eliminate biofilm. Furthermore, PQACs10‐co‐PEGMA10 micelles were applied as coatings using a dropwise method. The PEG chain formed hydration layer and the QACs chain for sterilization can hinders bacterial adhesion and proliferation, thereby preventing biofilm formation. The results show that the minimal inhibit concentration values and minimum biofilm eradication concentrations of the PQACs10‐co‐PEGMA10 micelles against Gram‐positive Staphylococcus aureus were 64 and 128 μg/mL, respectively. The antifouling and antibacterial rates of micelle coating against S. aureus were more than 99.99%. Taken together, the pH‐responsive PQACs10‐co‐PEGMA10 micelles demonstrate a good ability to clear and prevent biofilms, holding promise for complete biofilm removal and a reduction in biofilm‐related infections. [ABSTRACT FROM AUTHOR]

In this study, we describe the development of hydrogel formulations composed of micelles loading two natural antioxidants—resveratrol and rutin—and the evaluation of the effect of a by-product on the rheological and textural properties of the developed semi-solids. This approach aims to associate the advantages of hydrogels for topical administration of drugs and of lipid micelles that mimic skin composition for the delivery of poorly water-soluble compounds in combination therapy. Biomimetic micelles composed of L-α-phosphatidylcholine loaded with two distinct polyphenols (one non-flavonoid and one flavonoid) were produced using hot shear homogenisation followed by the ultrasonication method. All developed micelles were dispersed in a carbomer 940-based hydrogel to obtain three distinct semi-solid formulations, which were then characterised by analysing the thermal, rheological and textural properties. Olive pomace-based hydrogels were also produced to contain the same micelles as an alternative to respond to the needs of zero waste and circular economy. The thermograms showed no changes in the typical profiles of micelles when loaded into the hydrogels. The rheological analysis confirmed that the produced hydrogels achieved the ideal properties of a semi-solid product for topical administration. The viscosity values of the hydrogels loaded with olive pomace (hydrogels A) proved to be lower than the hydrogels without olive pomace (hydrogels B), with this ingredient having a considerable effect in reducing the viscosity of the final formulation, yet without compromising the firmness and cohesiveness of the gels. The texture analysis of both hydrogels A and B also exhibited the typical behaviour expected of a semi-solid system. [ABSTRACT FROM AUTHOR]

Background/Objectives: Glioblastoma is the most common and lethal primary brain tumor. Patients often suffer from tumor- and treatment induced vasogenic edema, with devastating neurological consequences. Intracranial edema is effectively treated with dexamethasone. However, systemic dexamethasone requires large doses to surpass the blood brain barrier in therapeutic quantities, which is associated with significant side effects. The aim of this study was to investigate a biodegradable, dextran-hydroxyethyl methacrylate (dex-HEMA) based hydrogel, containing polymeric micelles loaded with dexamethasone and liposomes encapsulating dexamethasone phosphate for localized and prolonged delivery. Methods: Poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide (mPEG-b-p(HPMA-Bz)) micelles were loaded with dexamethasone and characterized. The dexamethasone micelles, together with dexamethasone phosphate liposomes, were dispersed in an aqueous dex-HEMA solution followed by radical polymerization using a photoinitiator in combination with light. The kinetics and mechanisms of drug release from this hydrogel were determined. Results: The diameter of the nanoparticles was larger than the mesh size of the hydrogel, rendering them immobilized in the polymer network. The micelles immediately released free dexamethasone from the hydrogel for two weeks. The dexamethasone phosphate loaded in the liposomes was not released until the gel degraded and intact liposomes were released, starting after 15 days. The different modes of release result in a biphasic and sequential release profile of dexamethasone followed by dexamethasone phosphate liposomes. Conclusions: The results show that this hydrogel system loaded with both dexamethasone polymeric micelles and dexamethasone phosphate loaded liposomes has potential as a local delivery platform for the sequential release of dexamethasone and dexamethasone phosphate, for the intracranial treatment of glioblastoma associated edema. [ABSTRACT FROM AUTHOR]

Objectives: Micelles, liposomes, and solid lipid nanoparticles (SLNs) are promising drug delivery vehicles; however, poor aqueous stability requires post-processing drying methods for maintaining long-term stability. The objective of this study was to compare the potential of lipid-based micelles, liposomes, and SLNs for producing stable re-dispersible spray-dried powders with trehalose or a combination of trehalose and L-leucine. This study provides novel insights into the implementation of spray drying as a technique to enhance long-term stability for these lipid-based nanocarriers. Methods: Aqueous dispersions of LDV-targeted micelles, liposomes, and SLNs loaded with paclitaxel (PTX) were converted into re-dispersible powders using spray drying. The physicochemical properties of the nanocarriers were determined via scanning electron microscopy (SEM), Karl Fischer titration, differential scanning calorimetry (DSC), and dynamic light scattering (DLS). Short-term stability of all nanocarrier formulations was compared by measuring particle size, polydispersity index (PDI), and paclitaxel retention over 7 days at room temperature and at 4 °C. Results: Paclitaxel-loaded micelles, liposomes, and SLN formulations were successfully converted into well-dispersed spray-dried powders with acceptable yields (71.5 to 83.5%), low moisture content (<2%), and high transition temperatures (95.1 to 100.8 °C). SEM images revealed differences in morphology, where nanocarriers spray-dried with trehalose or a combination of trehalose and L-leucine produced smooth or corrugated particle surfaces, respectively. Reconstituted spray-dried nanocarriers maintained their nanosize and paclitaxel content over 7 days at 4 °C. Conclusions: The results of this study demonstrate the potential for the development of spray-dried lipid-based nanocarriers for long-term stability. [ABSTRACT FROM AUTHOR]

Inherited retinal disorders (IRDs) represent a group of challenging genetic conditions that often lead to severe visual impairment or blindness. The complexity of these disorders, arising from their diverse genetic causes and the unique structural and functional aspects of retinal cells, has made developing effective treatments particularly challenging. Recent advancements in gene therapy, especially non-viral nucleic acid delivery systems like liposomes, solid lipid nanoparticles, dendrimers, and polymersomes, offer promising solutions. These systems provide advantages over viral vectors, including reduced immunogenicity and enhanced targeting capabilities. This review delves into introduction of common IRDs such as Leber congenital amaurosis, retinitis pigmentosa, Usher syndrome, macular dystrophies, and choroideremia and critically assesses current treatments including neuroprotective agents, cellular therapy, and gene therapy along with their limitations. The focus is on the emerging role of non-viral delivery systems, which promise to address the current limitations of specificity, untoward effects, and immunogenicity in existing gene therapies. Additionally, this review covers recent clinical trial developments in gene therapy for retinal disorders. [ABSTRACT FROM AUTHOR]

[Display omitted] Antimicrobial resistance (AMR) is a pressing global health concern. ESKAPEE pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA) are notable of concern in healthcare settings due to their resistance to critical antibiotics. To combat AMR, the development of alternatives such as bacterial membrane-active agents is crucial. Fatty acids (FAs) have emerged as a sustainable, antibiotic-free solution with inherent antibacterial activity. However, long chain saturated fatty acids (LCFAs) sodium soaps exhibit poorly antibacterial properties in comparison to short chain FAs, believed to be linked to limited solubility in aqueous media. We employed choline as a chaotropic organic counter-ion to enhance the solubility of LCFAs and investigated their antibacterial effects against MRSA. The optimal medium conditions for micelle formation for LCFAs was first investigated. Then, we determined the critical micelle concentration (CMC), micellar morphology, and aggregation number through surface tension measurements and small angle neutron scattering experiments. Antimicrobial activity was assessed using minimum bactericidal concentration (MBC) assays and time-kill experiments. We have identified conditions where LCFAs are effective against MRSA for the first time, providing valuable insights for developing new antibacterial agents to fight AMR. LCFAs need to be used above their Krafft temperatures and CMC to exhibit antibacterial efficacy. [ABSTRACT FROM AUTHOR]

Polymeric patchy micelles (PPMs) are nanostructures with distinct regions on their surfaces, offering unique properties for various applications. Herein, we present a straightforward method for monitoring the structure of PPMs formed via non-covalent post-assembly modification (NCPAM). By employing 1-pyrenemethylamine, a pyrene-based molecule, as both a modifier and fluorescent probe, we demonstrate that the formation of PPMs with a higher order aggregation state of pyrene induces a stronger pyrene excimer emission. This leads to variations in the excimer-to-monomer emission ratio, serving as a parameter for studying structural changes in PPMs during NCPAM. In situ monitoring of PPM formation and temperature-dependent transformations is achieved using fluorescent analytical method, providing valuable insights into their structural evolution and dynamic behaviour. This study offers a straightforward approach to understanding and controlling PPM structures, facilitating the design of advanced nanomaterials for diverse applications. [ABSTRACT FROM AUTHOR]

Amphiphilic asymmetric brush copolymers (AABCs) possess unique self-assembly behaviors owing to their asymmetric brush architecture and multiple functionalities of multicomponent side chains. However, the synthesis of AABCs presents challenges, which greatly limits the exploration of their self-assembly behaviors. In this work, we employed dissipative particle dynamics (DPD) simulations to investigate the self-assembly behaviors of AABCs in selective solution. By varying the copolymer concentration and structure, we conducted the self-assembly phase diagrams of AABCs, revealing complex morphologies such as channelized micelles with one or more solvophilic channels. Moreover, the number, surface area, and one-dimensional density distribution of the channelized micelles were calculated to demonstrate the internal structure and morphological transformation during the self-assembly process. Our findings indicate that the morphology of the internal solvophilic channels is greatly influenced by the copolymer structure, concentration, and interaction parameters between the different side chains. The simulation results are consistent with available experimental observations, which can offer theoretical insights into the self-assembly of AABCs. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance (ABC) effect. We design three ionizable oligomers (IOs) that, with polylactide-polyethylene glycol (PLA-PEG), form a potential siRNA delivery system, named Ionizable Polymeric Micelles (IPMs). The siRNA encapsulated IPMs escape from lysosomes upon cellular uptake, and silence the target gene. A fibroblast activation protein inhibitor modified IPMs (FAPi-IPMs) show higher targeting for activated hepatic stellate cells (HSCs) compared to that for hepatocytes, silencing both HSP47 and HMGB1, reducing collagen secretion and liver inflammation, thereby treating fibrosis. Moreover, IPMs and FAPi-IPMs mitigate ABC effect and produce fewer PEG antibodies than LNPs, and show minimal apolipoprotein adsorption in vivo compared with LNPs, differentiating their targeting effects from LNPs. In conclusion, IPMs represent a nucleic acid delivery system with alternative targeting ability and reduced ABC effect. Authors develop a siRNA delivery system, named Ionizable Polymeric Micelles (IPMs) which employs a FAPi modification, enabling IPMs to target activated hepatic stellate cells, silencing target genes and treating liver fibrosis. [ABSTRACT FROM AUTHOR]

Ringy nanostructures are amazing materials, displaying unique optical, magnetic, and electronic properties highly related to their dimensions. A strategy capable of continuously tailoring the diameter of nanorings is the key to elucidating their structure‐function relationship. Herein, a method of bi‐component micellar‐configuration‐transformation induced by hydrophobicity for the synthesis of nanorings with diameters ranging from submicron (≈143 nm) to micron (≈4.8 µm) and their carbonaceous analogs is established. Remarkably, the nanorings fabricated with this liquid phase strategy achieve the record for the largest diameter span. Through varying the molecular lengths of fatty alcohols and copolymers, shortening the molecular length of fatty alcohol can swell the primary micelles, improve the exposure of hydrophobic component and boost the assembly kinetics for ultra‐large nanorings is shown here. On the other hand, shortening the molecular length of the copolymer will give rise to ultra‐small nanorings by reducing the size of primary micelles and shortening the assembly time. When assembling the nanorings into monolayer arrays and then depositing Au, such substrate displays enhanced surface‐enhanced Raman scattering (SERS) performance. This research develops a facile method for the controllable synthesis of ringy materials with multiscale tunable diameters and may inspire more interesting applications in physics, optical, and sensors. [ABSTRACT FROM AUTHOR]

A pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a "nano‐in‐micro drug delivery system". The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer. [ABSTRACT FROM AUTHOR]

This work aims to synthesize novel amphiphilic ionic liquids (AILs), AH‐PM, and AD‐PM as well as apply them to chemically demulsifying crude oil emulsions. Two AILs containing different long alkyl chains were synthesized and characterized using several techniques. The surface and interfacial indicated AILs' surface activity and ability to form micelles. For that, the demulsification efficacy (DE) of these AILs was explored using different factors affecting, e.g., AIL dose, settling time (ST), water content, and temperature. The results indicated that the AIL hydrophobicity resulting from the longer alkyl chain could improve AIL DE. Moreover, increased AIL dose, ST, water content, and temperature improved DE. [ABSTRACT FROM AUTHOR]

Robust and biocompatible hydrogels are recognized as promising biomimetic soft materials to improve human life quality. To ensure their stable, reliable, and safe service, the hydrogels are further required to have non‐contact and wireless stress sensing ability. Herein, a mechanoluminescence (ML) based micellar hydrogel is developed, in which the surface‐modified BaSi2O2N2: Eu2+ (M‐BSON) particles are chemically incorporated into the cross‐linked polyacrylamide/polymethyl acrylate (PAM/PMA) network structure. Because of the interactions between the M‐BSON particles and the PMA micelles, the as‐fabricated composite hydrogel exhibits enhanced mechanical properties with a mechanical strength of 2.73 MPa and a toughness of 3.40 MJ m−3, respectively. The chemical wrapping of the M‐BSON particles by the hydrophobic PMA micelles further protects the ML properties from water quenching, leading to remarkable stress‐induced luminescence under the water environment of hydrogel. Because of its desirable mechanical performance, attractive stress‐light responsiveness, and good biocompatibility, the M‐BSON incorporated hydrogel has the potential to be applied as an intelligent artificial ligament for stress self‐monitoring and failure warning. This work addresses the inhomogeneous dispersion and water quenching issues of the ML particles in hydrogel structure, which significantly promote ML applications in bionic engineering. [ABSTRACT FROM AUTHOR]

Background/Objectives: A range of NMR techniques, including diffusion ordered spectroscopy (DOSY) were used to characterise complex micelles formed by the anti-microbial cationic surfactant cetylpyridium chloride and to quantify the degree of interaction between cetylpyridium chloride and hydroxyethyl cellulose in a variety of commercially relevant formulations as a model for the disk retention assay. Methods: This NMR-derived binding information was then compared with the results of formulation analysis by traditional disk retention assay (DRA) and anti-microbial activity assays to assess the suitability of these NMR techniques for the rapid identification of formulation components that could augment or retard antimicrobial activity DRA. Results: NMR showed a strong ability to predict anti-microbial activity for a diverse range of formulations containing cetylpyridinium chloride (CPC). Conclusions: This demonstrates the value of this NMR-based approach as a rapid, relatively non-destructive method for screening commercial experimental anti-microbial formulations for efficacy and further helps to understand the interplay of excipients and active ingredients. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) is extracted from the dried rhizome of Curcuma longa. It is cost-effective and easily accessible, exhibiting vibrant hues. Moreover, it encompasses a wide range of activities including anti-inflammatory, antioxidant, and anticancer properties. However, the application of CUR is constrained by its limited water solubility and low bioavailability. The amphiphilic copolymer poly (ethylene glycol) -b-poly (ε-caprolactone) (PEG-PCL) was employed for the preparation of micelles to solve these issues. The formation mechanism, drug loading performance, stability, release and cellular uptake of PEG-PCL micelles were comprehensively evaluated. A series of micelles based on PEG-PCL with different molecular weights(PEG2K-PCL3.5K, PEG2K-PCL5K, PEG5K-PCL3K,PEG5K-PCL5K, PEG5K-PCL13K) showed high encapsulation efficiency. The encapsulation efficiency of PEG2K-PCL5K reached 98.38±3.06%, demonstrating high efficacy in encapsulation. The encapsulation of PEG-PCL significantly enhanced the dissolution rate of CUR and exhibited a sustained release effect, concurrently augmenting the antioxidant capacity of CUR. The micelles exhibit a transparent appearance, demonstrating excellent stability, and they can be re-dispersed in water after freeze-drying. PEG-PCL micelles demonstrated the excellent biocompatibility and could be internalized by enterocyte. Meanwhile, the molecular weight of PEG-PCL was correlated with the particle size, encapsulation efficiency, drug loading performance, and cellular uptake efficiency of micelles. In summary, the utilization of PEG-PCL micelles enhanced the solubility, stability, and cellular uptake of CUR, there by offering potential strategies for the efficient delivery of hydrophobic bioactive molecules. [ABSTRACT FROM AUTHOR]

PMMA-b-PEO-b-PMMA tri-block copolymers were synthesized by anionic polymerization technique usingtelechelic1,1-diphenylethylene-terminated poly (ethylene oxide)as macroinitiators and Sec-BuLi four tri-block copolymers of PMMA-b-PEO-b-PMMA with different number average molecular weight ( M ¯ n ) were synthesized, and the structure of the macroinitiators and polymers was confirmed by FTIR. and1H NMR spectroscopic methods. Through the solvent-induced association, the aqueous solutions of PMMA-b-PEO-b-PMMA were formed. After that, hydrodynamic diameter, DLS and TEM were used to study the morphology of the resulting aqueous solutions. The polymer's self-assembled nanostructures of core-shell flower-like spherical micelles structures were observed. Also, the PMMA hydrophobic content of the tri-block increases steadily and the core size of the micelles decreases significantly, due to reverse micelle formation in which the core is hydrophobic PMMA blocks and the corona is PEO block. This micelle is an excellent detector for metal ions and acts as a reducing agent for them to convert into pure nontoxic nanoparticles. [ABSTRACT FROM AUTHOR]