Micellar curcumol for maintenance therapy of ovarian cancer by activating the FOXO3a.

Maintenance therapy (MT) for ovarian cancer (OC) is crucial for preventing disease relapse. Curcumol shows effective anti-OC ability and low-toxicity to the normal ovarian epithelial cells, however, its bioavailability is low. Herein, micellar loaded curcumol (MC) was prepared and the anti-tumor ability of MC were performed on OC cells. The results indicated that the IC50 values of MC in two kinds of OC cells were 37.69 ±â€¯2.43 and 28.54 ±â€¯1.58 µg/mL, respectively. Mechanistically, curcumol could interact with the AKTThr308 site, inhibiting the phosphorylation of FOXO3a, which promoted FOXO3a nuclear locating and recruited it to the PERK promoter, activating the ERS induced apoptosis pathway. Moreover, MC inhibited the growth of SKOV3 cells on tumor-bearing nude mice and the DiR-labeled MC could quickly accumulate in the tumor region. MC provides great feasibility to achieve efficient MT for OC based on the nanoplatforms of active ingredients from natural products.

Tumoral Pharmacokinetic-Pharmacodynamic Simulation of Doxorubicin-Encapsulated Polymeric Micelles Using a Tissue-Isolated Tumor Perfusion System.

Pharmacokinetic (PK) elucidation of polymeric micelles delivering anticancer drugs is crucial for accurate antitumor PK-pharmacodynamic (PK-PD) simulations. Particularly, establishing a methodology to quantify the tumor inflow and outflow of anticancer drugs encapsulated in polymeric micelles is an essential challenge. General tumor biodistribution experiments are disadvantageous in that inflow quantification is easy, but outflow quantification is challenging. We addressed this issue by proposing a quantification method that combines a tissue-isolated tumor perfusion system with microdialysis. This method aims to determine tumoral drug inflow and outflow by quantifying the drugs released from the polymeric micelles via a tumor-embedded microdialysis probe and perfusate, respectively. Furthermore, we evaluated the feasibility of this method by perfusing pH-sensitive polyethylene glycol-poly(aspartate-hydrazone-doxorubicin/phenylalanine)n (PPDF-Hyd-DOX) in a tissue-isolated tumor perfusion system, and we quantified tumor inflow and outflow released DOX. Based on the quantitative results, we performed compartmental analyses by incorporating the gamma-distributed delay function and calculated the PK rate constants. These parameters were input into a tumor-bearing rat compartment model for ex vivo-in vivo extrapolation (EVIVE) of the rat plasma PPDF-Hyd-DOX concentrations and simulated intratumorally released DOX concentrations. The simulation profiles demonstrated a good fit with the Walker 256 intratumoral released DOX concentration profiles previously reported. This EVIVE-PK model was coupled with the threshold natural-growth tumor PD model, and PK-PD analysis was performed. This model exhibited a better fit to the tumor weight profile of Walker 256-bearing rats treated with PPDF-Hyd-DOX than that of our previously reported PK-PD model. Thus, EVIVE, based on a tissue-isolated tumor perfusion system with microdialysis, is a promising approach for the PK-PD simulation of polymeric micelle anticancer therapy.

Advanced nanoparticles in osteoarthritis treatment.

Osteoarthritis (OA) is the most prevalent degenerative joint disorder, affecting hundreds of millions of people globally. Current clinical approaches are confined to providing only symptomatic relief. Research over the past two decades has established that OA is not merely a process of wear and tear of the articular cartilage but involves abnormal remodelling of all joint tissues. Although many new mechanisms of disease have been identified in the past several decades, the efficient and sustainable delivery of drugs targeting these mechanisms in joint tissues remains a major challenge. Nanoparticles recently emerged as favoured delivery vehicles in OA treatment, offering extended drug retention, enhanced drug targeting, and improved drug stability and solubility. In this review, we consider OA as a disease affecting the entire joint and initially explore the pathophysiology of OA across multiple joint tissues, including the articular cartilage, synovium, fat pad, bone, and meniscus. We then classify nanoparticles based on their composition and structure, such as lipids, polymers, inorganic materials, peptides/proteins, and extracellular vesicles. We summarise the recent advances in their use for treatment and diagnosis of OA. Finally, we discuss the current challenges and future directions in this field. In conclusion, nanoparticle-based nanosystems are promising carriers that advance OA treatment and diagnosis.

Domain swapping: a mathematical model for quantitative assessment of structural effects.

The domain-swapping mechanism involves the exchange of structural elements within a secondary or supersecondary structure between two (or more) proteins. The present paper proposes to interpret the domain-swapping mechanism using a model that assesses the structure of proteins (and complexes) based on building the structure of a common hydrophobic core in a micelle-like arrangement (a central hydrophobic core with a polar shell in contact with polar water), which has a considerable impact on the stabilisation of the domain structure built by domain swapping. Domains with a hydrophobicity system that is incompatible with the micelle-like structure have also been identified. This incompatibility is the form of structural codes related to biological function.

A Multifunctional Nanodrug Increases the Therapeutic Sensitivity of Lenvatinib to Hepatocellular Carcinoma by Inhibiting the Stemness of Hepatic Cancer Stem Cells.

Drug resistance resulting from diverse mechanisms including the presence of cancer stem cells (CSCs) is the main obstacle for improving therapeutic efficacy of lenvatinib in hepatocellular carcinoma (HCC). Herein, a nanomedicine (siCD24-Len-MnO@PLAP) is developed by incorporating manganese oxide (MnO), lenvatinib (Len), and siRNA against CD24 (siCD24) into micelles composed of methoxypolyethylene glycol (mPEG), poly-L-lysine (PLLys), and polyasparagyl(N-(2-Aminoethyl)piperidine) (PAsp(PIP)) triblock copolymer. The nanomedicine can respond to the tumor microenvironment (TME) to release lenvatinib, and produce Mn2+ and O2, accompanied by changes in nanoparticle charge, which facilitates cellular endocytosis of siCD24-loaded nanoparticles. The released siCD24 and lenvatinib synergistically reduces CD24 expression, resulting in a more pronounced inhibition of stemness of CSCs. In the mouse models of HCC using Huh7-derived CSCs and Hepa1-6-derived CSCs, the nanomedicine shows remarkable anti-cancer effect by enhancing the therapeutic effects of lenvatinib against HCC via reducing the expression level of CD24 and decreasing the expression of hypoxia inducible factor-1α (HIF-1α). Moreover, in situ production of paramagnetic Mn2+ from the nanomedicine serves as an excellent contrast agent for magnetic resonance imaging (MRI) to monitor the therapeutic process. This study demonstrates that this multifunctional MRI-visible siCD24- and lenvatinib-loaded nanodrug holds great potential in enhancing therapeutic sensitivity for HCC lenvatinib therapy.

Remote-controlled dexamethasone-duration on eye-surface with a micelle-magnetic nanoparticulate co-delivery system for dry eye disease.

Dexamethasone (DEX) is used to treat ocular surface diseases. However, regulating DEX duration in tears while preventing its absorption into the anterior chamber is critical for balancing its therapy effects and the side effects. In this study, a novel magnetic nanoparticle (MNP)-micelle (MC) co-delivery system (MMDS) was developed. The MC moiety in the MMDS served as the carrier for DEX and the MNP part endowed the MMDS with magnetic-responsive properties. To extend its residency, the MMDS was magnetically attracted by an external magnet after instilling, which acted as a precorneal drug-depot enabling a sustainable release of DEX in tears. With combination of magnet treatment, the topical instillation of MMDS@DEX significantly prolonged the DEX-retention in tears and increased the DEX-concentration in the cornea and conjunctiva, as well as concurrently reduced the DEX-level in the aqueous humor, when compared with the commercial DEX eye drop treatment. The combination of MMDS@DEX and magnet treatment exerted significantly better therapeutic effects against DED with smaller side effects than conventional treatments including DEX suspension, commercial DEX eye drops, as well as the MMDS@DEX treatment alone. The present work provided a new method for the effective delivery of DEX to ocular surface tissues while reducing its side effects, which will be beneficial to the treatments of a wide range of ocular surface diseases.

Do ethoxylated polymeric coacervate micelles respond to temperature similarly to ethoxylated surfactant aggregates?

HYPOTHESIS: Ethoxylated complex coacervate core micelles (C3Ms), formed by the electrostatic coacervation of a charge-neutral diblock copolymer and an oppositely charged homopolymer, exhibit morphology governed by molecular packing principles. Additionally, this morphology is temperature-dependent, leading to transitions similar to those observed in classical ethoxylated surfactant aggregates. EXPERIMENTS: To explore the thermal effects on the size and morphology of C3Ms, we employed dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). These techniques were applied to C3Ms formed by copolymers with varying poly(ethylene oxide) (EO) lengths. FINDINGS: Increasing the temperature-induced a transition from spherical to elongated aggregates, contingent on the EO block length. This morphological transition in EO-containing C3Ms parallels the behavior of classical ethoxylated surfactant aggregates. Despite the fundamental differences between hydrophobically driven and electrostatic coacervate micelles, our findings suggest that similar molecular packing principles are universally applicable across both systems. Our results offer valuable insights for predicting the structural properties of these coacervate platforms, which is crucial for envisioning their future applications.

Molecular identification of rhamnolipids produced by Pseudomonas oryzihabitans during biodegradation of crude oil.

Introduction: The ability to produce biosurfactants plays a meaningful role in the bioavailability of crude oil hydrocarbons and the bioremediation efficiency of crude oil-degrading bacteria. This study aimed to characterize the produced biosurfactants by Pseudomonas oryzihabitans during the biodegradation of crude oil hydrocarbons. Methods: The biosurfactants were isolated and then characterized by Fourier transform infrared (FTIR), liquid chromatography-mass-spectrometry (LC-MS), and nuclear magnetic resonance spectroscopy (NMR) analyses. Results: The FTIR results revealed the existence of hydroxyl, carboxyl, and methoxyl groups in the isolated biosurfactants. Also, the LC-MS analysis demonstrated a main di-rhamnolipid (l-rhamnopyranosyll-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoate, Rha-Rha-C10-C10) along with a mono-rhamnolipid (l-rhamnopyranosyl-b-hydroxydecanoylb-hydroxydecanoate, Rha-C10-C10). In agreement with these findings, the NMR analysis confirmed the aromatic, carboxylic, methyl, sulfate moieties, and hexose sugar in the biosurfactants. The emulsion capacity of the biosurfactants decreased the surface tension of the aqueous system from 73.4 mN m-1 to around 33 mN m-1 at 200 mg L-1 as the critical micelle concentration. The emulsification capacity of the biosurfactants in the formation of a stable microemulsion for the diesel-water system at a wide range of pH (2-12), temperature (0-80°C), and salinity (2-20 g L-1 of NaCl) showed their potential use in oil recovery and bioremediation through the use of microbial enhancement. Discussion: This work showed the ability of Pseudomonas oryzihabitans NC392 cells to produce rhamnolipid molecules during the biodegradation process of crude oil hydrocarbons. These biosurfactants have potential in bioremediation studies as eco-friendly and biodegradable products, and their stability makes them optimal for areas with extreme conditions.

Aqueous Photocatalytic Oxidation of Thioethers with Polydiacetylene Micelle Nanoreactors.

A semi-heterogeneous photocatalytic system was assembled through encapsulation of a lipophilic porphyrin in stabilized polydiacetylene micelles. The colloidal nanohybrid catalyst was valorized in the aerobic photo-oxidation of sulfides to the corresponding sulfoxides. Micelles behaved as nanoreactors by creating a favorable environment for the photo-activation of oxygen nearby thioethers and subsequent sulfoxidation. The process operates selectively under visible light and air atmosphere, with low catalytic loading and in water as the only solvent.

Interaction of drug molecules with surfactants below (Benesi-Hildebrand equation) and above the critical micelle concentration (Kawamura equation).

Drug molecules can interact with surfactant molecules either in their monomeric form, where the Benesi-Hildebrand equation determines the binding constant, or when a micellar pseudophase is formed, where the Kawamura equation assesses the partition coefficient. Benesi-Hildebrand plots represent the differential absorbance as a function of surfactant concentration below the critical micelle concentration (CMC), while Kawamura plots show this relationship above the CMC, where the drug can influence the CMC and needs consideration. This review aims to provide an overview of methods for evaluating drug-surfactant interactions in aqueous solutions, particularly below and above the CMC, using spectroscopic data. Understanding these interactions is crucial for pharmacodynamics, affecting drug binding, enzymatic activity, and formulation. Various surfactants were analyzed with diphenhydramine hydrochloride, levofloxacin, phenothiazine, moxifloxacin, and chlorpromazine hydrochloride to determine monomeric binding constants, while sulfathiazole, sodium valproate, cefotaxime, losartan, and metformin hydrochloride were assessed for partitioning coefficient values. Errors in Benesi-Hildebrand plots may arise from considering surfactant concentrations above the CMC, while mistakes in Kawamura plots may stem from neglecting to determine the CMC in the presence of drug molecules, which can alter the surfactant's behavior.

Mesoporous PtIr alloy single-particle: A novel SECM-tip for in situ monitoring NO of single-cell.

As a vital factor in cell metabolism, nitric oxide (NO) is associated with nitrosative stress and subsequent inflammations and diseases. In situ, real-time NO monitoring is challenging due to its relative trace concentration and fast diffusion in cell. Scanning electrochemical microscopy (SECM) is suited uniquely for single-cell analysis, and its electrochemical response to targets can be further enhanced by improving the interfacial properties of its tip. Here, an ultramicroelectrodes (UMEs) modification strategy based on bimetallic single-particle was proposed for the first time. This mesoporous platinum/iridium alloy single-particle (mPtIr SP) interface using micelle-assisted electrodeposition was characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). And the nucleation kinetic progress which can be defined as "oil-in-water-like" electrodeposition was discussed in detail. The high sensitivity (203.86 µA/µM·cm2) and good selectivity for NO detection benefits from the high catalysis of the PtIr alloy and the high mass transfer properties of the porous interface. In particular, this novel UME can real-time monitor NO release from a single MCF-7 cell stimulated by perfluorooctanoic acid (PFOA), providing new ideas for contaminant toxicity assessment, health diagnostics, and disease treatment.

Oil-water interfacial behaviour of different caseins and stability of emulsions: Effect of micelle content and caseins concentrations.

This study aimed to investigate the interfacial behaviour of caseins in different micelle content and its effect on the stability of emulsions, including micellar casein concentrate (MCN), calcium caseinate (CaC) and sodium caseinate (NaC). Results revealed that at high protein concentrations (0.5 %-2.5 %), MCN, CaC and NaC exhibited similar interfacial behaviour as well as unfolding rate constants (k 1 ) of 3.11-3.41 × 10-4 (s-1), 2.96-3.35 × 10-4 (s-1) and 2.75-3.27 × 10-4 (s-1), respectively. The interfacial layer formed was dominated by non-micelles, and microscopic images revealed the thickness of the interfacial layer to be 10-20 nm. By contrast, at low concentrations, the differences in the slope of E-π curves and k 1 indicated that the micelle content of casein affects protein interfacial behaviour and properties and that micellar casein is involved in the formation of the interfacial layer. The formation of large numbers of droplets during emulsion preparation results in a similar low concentration environment. Cryo-TEM showed adsorption of micellar casein in all three casein-stabilised emulsions, and the amount of adsorption was proportional to the micelle content. NaC has faster adsorption and rearrangement rates due to fewer micelles and more non-micelles, so that NaC forms smaller droplets and more stable emulsions than those formed by MCN and CaC within the range of 0.5 % to 2.0 %.

Cancer-associated fibroblasts barrier breaking via TGF-ß blockade paved way for docetaxel micelles delivery to treat pancreatic cancer.

TGF-ß is a crucial regulator in tumor microenvironment (TME), especially for myofibroblastic cancer-associated fibroblasts (myCAFs). The myCAFs can be motivated by TGF-ß signaling to erect pro-tumor TME, meanwhile, myCAFs overexpress TGF-ß to mediate the crosstalk between tumor and stromal cells. The blockade of TGF-ß can break cancer-associated fibroblasts barrier, consequently opening the access for drugs into tumor. The TGF-ß is a promising target in anti-tumor therapy. Herein, we introduced a two-stage combination therapy (TC-Therapy), including TGF-ß receptor I inhibitor SB525334 (SB) and cytotoxicity agent docetaxel micelle (DTX-M). We found that SB and DTX-M synergistically inhibited myCAFs proliferation and elevated p53 protein expression in BxPC-3/3T3 mixed cells. Gene and protein tests demonstrated that SB cut off TGF-ß signaling via receptor blockade and it did not arouse TGF-ß legend compensated internal autocrine. On the contrary, two agents combined decreased TGF-ß secretion and inhibited myCAFs viability marked by α-SMA and FAPα. TC-Therapy was applied in BxPc-3/3T3 mixed tumor-bearing mice model. After TC-Therapy, the α-SMA+/ FAPα+ myCAFs faded increasingly and collagenous fibers mainly secreted by myCAFs decreased dramatically as well. More than that, the myCAFs barrier breaking helped to normalize micro-vessels and paved way for micelle penetration. The TGF-ß protein level of TC-Therapy in TME was much lower than that of simplex DTX-M, which might account for TME restoration. In conclusion, TGF-ß inhibitor acted as the pioneer before nano chemotherapeutic agents. The TC-Therapy of TGF-ß signaling inhibition and anti-tumor agent DTX-M is a promising regimen without arising metastasis risk to treat pancreatic cancer. The therapeutic regimen focused on TGF-ß related myCAFs reminds clinicians to have a comprehensive understanding of pancreatic cancer.

Micelle-encapsulated IR783 for enhanced photothermal therapy in mouse breast cancer.

BACKGROUND: Photothermal therapy, an emerging cancer treatment, selectively eliminates lesions using photothermal compounds that convert light into heat. IR783, a near-infrared fluorescent heptamethine cyanine dye, has been used to achieve selective hyperthermic effects in target tissues via near-infrared irradiation. To implement IR783 as a photothermal agent, IR783 biodistribution must be calibrated to achieve a constant and uniform concentration in target cells. Accordingly, we developed micelle-encapsulated IR783 (IR783 micelles) and evaluated their effectiveness as photothermal drugs. METHODS: In vitro, the photothermic effects of free IR783 and IR783 micelle solutions induced by near-infrared light irradiation were analyzed. Additionally, we investigated the mechanism of cell death mediated by photothermal therapy using free IR783 and IR783 micelles in mouse breast cancer (EMT6) cells. In vivo, the efficacy of photothermal therapy with both free IR783 and IR783 micelles was examined in EMT6-bearing mice. RESULTS: In vitro, the temperature of free and micelle-encapsulated IR783 solutions increased after near-infrared irradiation. Near-infrared irradiation with free IR783 and IR783 micelles induced cytotoxicity in cancer cells by generating heat. In vivo, IR783 micelles elicited more preferential tumor tissue uptake and enhanced the antitumor effects of photothermal therapy at a lower light dose relative to free IR783. CONCLUSIONS: Overall, these results suggest that IR783 micelles could accumulate in mouse breast cancer tissues and exhibit enhanced antitumor effects when used as a photothermal therapy, with superior effects obtained at 2.1 W/cm2 (252 J/cm2) compared with that of free IR783.

Phytochemical-Based Nanoantioxidants Stabilized with Polyvinylpyrrolidone for Enhanced Antibacterial, Antioxidant, and Anti-Inflammatory Activities.

Despite the inhibitory effect of phytoncide (Pht) on food-borne pathogenic bacterial growth, the hydrophobic nature and susceptibility to biodegradation under physiological conditions limits its applications. Here, we developed Pht-loaded polyvinylpyrrolidone (PVP) micelles (Pht@PVP MC) via micelle packing. Pht was solubilized using different types of PVP as micellar vehicles. The as-prepared Pht@PVP MCs were characterized using dynamic light scattering and transmission electron microscopy. The sizes of the Pht@PVP MCs were controlled from 301 ± 51 to 80 ± 3 nm by adjusting the PVP content. The polydispersity index of Pht@PVP MC was between 0.21 ± 0.03 and 0.16 ± 0.04, indicating homogeneous size. A colony-counting method was employed to evaluate the improvement in antibacterial activity after Pht encapsulation in PVP micelles. The reactive oxygen species (ROS)-scavenging activity and anti-inflammatory efficacy of Pht@PVP MC were analyzed in a concentration range of 10-100 µg/mL by evaluating in vitro ROS and nitric oxide levels using DCFDA and Griess reagents. PVP with both hydrophobic and hydrophilic moieties improved the aqueous solubility of Pht and stabilized it via steric hindrance. Higher-molecular-weight PVP at higher concentrations resulted in a smaller hydrodynamic diameter of Pht@PVP MC with uniform size distribution. The spherical Pht@PVP MC maintained its size and polydispersity index in a biological buffer for 2 weeks. Pht@PVP MC exhibited enhanced antibacterial activity compared to bare Pht. The growth of Staphylococcus aureus was effectively inhibited by Pht@PVP MC treatment. Furthermore, biocompatible Pht@PVP MC exhibited dose-dependent antioxidant and anti-inflammatory activities in vitro. Overall, Pht@PVP MC is an effective alternative to synthetic antibacterial, antioxidant, and anti-inflammatory chemicals.

Influence of Linear Diamine Counterions on the Self-Assembly of Glycine-, Alanine-, Valine-, and Leucine-Based Amphiphiles.

Electrical conductimetry and dynamic light scattering (DLS) were used to investigate the aggregation behaviors of four amino acid-based surfactants (AABSs; undecanoyl-glycine, undecanoyl-l-alanine, undecanoyl-l-valine, undecanoyl-l-leucine) in the presence of five linear diamine counterions (1,2-diaminoethane, 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, 1,6-diaminohexane). Electrical conductimetry was used to measure the CMCs for each system, which ranged from 5.1 to 22.5 mM. With respect to counterions, the obtained CMCs decreased with increases in the interamine spacer length; this was attributed to the improved torsional binding flexibility in longer counterions. Strong linear correlations (mean R2 = 0.9443) were observed between the CMCs and predicted surfactant partition coefficients (logP; water/octanol), suggesting that micellization is primarily driven by the AABS's hydrophobicity for these systems. However, significant deviations in this linear relationship were observed for systems containing 1,2-diaminoethane, 1,4-diaminobutane, and 1,6-diaminohexane (p = 0.0774), suggesting altered binding dynamics for these counterions. pH measurements during the CMC determination experiments indicated the full deprotonation of the AABSs but did not give clear insights into the counterion protonation states, thus yielding an inconclusive evaluation of their charge stabilization effects during binding. However, DLS measurements revealed that the micellar size remained largely independent of the counterion length for counterions longer than 1,2-diaminoethane, with hydrodynamic diameters ranging from 2.2 to 2.8 nm. This was explained by the formation of charge-stabilized noncovalent dimers, with each counterion bearing a full +2 charge. Conductimetry-based estimates of the degrees of counterion binding (ß) and free energies of micellization (ΔG°M) revealed that bulky AABSs exhibit preferential binding to counterions with an even number of methylene groups. It is proposed that when these counterions form noncovalent dimers, perturbations in their natural geometries result in the formation of a binding pocket that accommodates the AABS steric bulk. While the direct application of these systems remains to be seen, this study provides valuable insights into the structure-property relationships that govern AABS aggregation.

Why Do Ionic Surfactants Significantly Alter the Chemiluminogenic Properties of Acridinium Salt?

Acridinium esters, due to their capability for chemiluminescence (CL), are employed as indicators and labels in biomedical diagnostics and other fields. In this work, the influence of ionic surfactants, hexadecyltrimethylammonium chloride and bromide (CTAC and CTAB, cationic) and sodium dodecyl sulphate (SDS, anionic) on the CL parameters and mechanism of representative emitter, 10-methyl-9-[(2-methylphenoxy)carbonyl]acridinium trifluoromethanesulphonate (2MeX) in a H2O2/NaOH environment, is studied. Our investigations revealed that the type of surfactant and its form in solution have an impact on the CL kinetic constants and integral efficiencies, while changes in those emission properties resulting from the type of ion (Cl- vs. Br-) are negligible. The major changes were recorded for systems containing surfactants at concentrations higher than the critical micelle concentration. The cationic surfactants (CTAC, CTAB) cause a substantial increase in CL emission kinetics and a moderate increase in its integral efficiency. At the same time, the opposite effect is observed in the case of SDS. Molecular dynamics simulations suggest that changes in emission parameters are likely due to differences in the binding strength of 2MeX substrate with surfactant molecules, which is higher for SDS than for CTAC. The results can help in rational designing of optimal acridinium CL systems and demonstrate their usefulness in distinguishing the pre- and post-micellar environment and the charge of surfactants.

Biological Fate Tracking of Nitric Oxide-Propelled Microneedle Delivery System Using an Aggregation-Caused Quenching Probe.

Nanoparticle-loaded dissolving microneedles (DMNs) have attracted increasing attention due to their ability to provide high drug loading, adjustable drug release behavior, and enhanced therapeutic efficiency. However, such delivery systems still face unsatisfied drug delivery efficiency due to insufficient driving force to promote nanoparticle penetration and the lack of in vivo fate studies to guide formulation design. Herein, an aggregation-caused quenching (ACQ) probe (P4) was encapsulated in l-arginine (l-Arg)-based nanomicelles, which was further formulated into nitric oxide (NO)-propelled nanomicelle-integrated DMNs (P4/l-Arg NMs@DMNs) to investigate their biological fate. The P4 probe could emit intense fluorescence signals in intact nanomicelles, while quenching with the dissociation of nanomicelles, providing a "distinguishable" method for tracking the fate of nanomicelles at a different status. l-Arg was demonstrated to self-generate NO under the tumor microenvironment with excessive reactive oxygen species (ROS), providing a pneumatic force to promote the penetration of nanomicelles in both three-dimensional (3D)-cultured tumor cells and melanoma-bearing mice. Compared with passive microneedles (P4 NMs@DMNs) without a NO propellant, the P4/l-Arg NMs@DMNs possessed a good NO production performance and higher nanoparticle penetration capacity. In conclusion, this study offered an ACQ probe-based biological fate tracking approach to demonstrate the potential of NO-propelled nanoparticle-loaded DMNs in penetration enhancement for topical tumor therapy.

Evaluation of Anticancer Efficacy of D-α-Tocopheryl Polyethylene-Glycol Succinate and Soluplus® Mixed Micelles Loaded with Olaparib and Rapamycin Against Ovarian Cancer.

Purpose: Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer. Methods: We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system. Results: OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was >65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (**p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo. Conclusion: Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer.

Preparation and Study of the Physicochemical and Functional Properties of Nano/Micromicellar Structures Containing Chokeberry Fruit Pomace Extracts Using Egg White and Egg Yolk.

There is currently a growing interest in health-promoting foods. The beneficial effects of food on human health are actively promoted by health professionals and nutritionists. This growing awareness is influencing the increasing range of functional foods and the pursuit of more innovative solutions. Recent research indicates that spherical nanoparticles have the potential to be used as functional biomaterials in the food industry, particularly for encapsulating hydrophobic natural phytochemicals. Techniques and systems based on micro- and nano-encapsulation are of great importance in the food and pharmaceutical industries. It is of paramount importance that encapsulation materials are safe for use in food. The aim of this study was to obtain micelles containing extracts from chokeberry fruit pomace using egg yolk powder (EYP) for emulsification (as a source of lecithin) and egg white powder (EWP) for stabilisation. The structural properties of the micelles in the resulting powders were characterised using Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) analysis confirmed the presence of spherical micellar structures between 500 and 1000 nm in size. The water activity and water content of the obtained powders were determined, and the thermal (DSC) and antioxidant properties were investigated. The results indicated that the powder with the micellar structures had a higher stability compared to the powder obtained by simple mixing without the use of encapsulation techniques.