Nanoemulsions in Skin Cancer Therapy: A Promising Frontier.

Skin cancer, a global burden for particularly white people, is classified as various histopathological types, including malignant melanoma, basal and squamous cell carcinoma, on the basis of affected different skin layers. Clinical adjuvant therapy (electro-chemotherapy, radio- and immuno therapy), surgical techniques (Cryosurgery, laser treatment, dermabrasion, Moh's micrographic surgery), photodynamic treatment and theranostic approaches are confined only for the treatment of serious health issues. Therefore, nanotechnology based approaches, especially nanoemulsion, a non-spontaneous, transparent or translucent, kinetically stable nanostructured (1-1000nm) colloidal dispersion (comprised of oil, water and surfactant/cosurfactant), are being popularised as a potential topical nanocarrier to deliver BCS class II and IV anti-neoplastic drugs attributing to its capacity for both active and passive tumor targeting in controlled or sustained manner and improving bioavailability via enhancing permeabilityretention effect with minimal adverse effects. Numerous research on nanoemulsion for the treatment of both melanoma and non-melanoma skin cancer is only limited to preclinical stages as several physiological variables reduce the effectiveness of nanoemulsion via restricting topical penetration.

Radiation and Radical Grafting Compatibilization of Polymers for Improved Bituminous Binders-A Review.

This review scrutinizes current research on new methods for enhancing bituminous binder performance through radiation and radical grafting of polymer modifiers of bitumen. It investigates innovative methods, including using waste polymers as modifiers and applying radiation for polymer grafting, to overcome challenges like high costs, low aging resistance, and storage stability issues, of which separation of phases polymer/bitumen is the most significant obstacle. These advanced modification techniques promise sustainability through the decrease of the carbon footprint of transportation systems by improving the properties and durability of binders. Additionally, this review discusses the parameters and mechanistic aspects from a scientific perspective, shedding light on the underlying processes that contribute to the improved performance of modified bituminous binders.

Synthesis of Hydrophilic Poly(vinylpyrrolidone)/CuS Free-Standing Thin Films Exhibiting Photothermal Conversion.

Free-standing films without the need for any support materials attract attention because of their excellent flexibility in use and ability to be transferred to various substrates. However, free-standing films containing large amounts of inorganic crystalline particles are hard to achieve due to their low strength. In this study, we found the possibility of preparing a free-standing composite film of CuS/polyvinylpyrrolidone (PVP) at a large loading of CuS (>50%) from a concentrated colloidal dispersion of CuS nanoparticles modified with PVP. Despite the large amount of inorganic crystals contained in the free-standing film, the film was strong enough to be handled without any support materials. As a proof-of-concept application of the free-standing film, a solar water evaporation experiment was performed. The CuS/PVP free-standing film exhibited photothermal conversion under light illumination to generate heat and accelerate water evaporation, achieving an evaporation rate of 4.35 kg·m-2 h-1 and an evaporation efficiency of 96.3% at a power density of 3 suns. In addition, thanks to the free-standing feature, one side of the CuS/PVP film could be hydrophobized with polydimethylsiloxane to form a Janus thin film, allowing for floating on the water surface. As a result, effective water evaporation was achieved because of the selective evaporation of water from the air/water interface.

Design of High-Payload Ascorbyl Palmitate Nanosuspensions for Enhanced Skin Delivery.

A high-payload ascorbyl palmitate (AP) nanosuspension (NS) was designed to improve skin delivery following topical application. The AP-loaded NS systems were prepared using the bead-milling technique, and softly thickened into NS-loaded gel (NS-G) using hydrophilic polymers. The optimized NS-G system consisted of up to 75 mg/mL of AP, 0.5% w/v of polyoxyl-40 hydrogenated castor oil (Kolliphor® RH40) as the suspending agent, and 1.0% w/v of sodium carboxymethyl cellulose (Na.CMC 700 K) as the thickening agent, in citrate buffer (pH 4.5). The NS-G system was embodied as follows: long and flaky nanocrystals, 493.2 nm in size, -48.7 mV in zeta potential, and 2.3 cP of viscosity with a shear rate of 100 s-1. Both NS and NS-G provided rapid dissolution of the poorly water-soluble antioxidant, which was comparable to that of the microemulsion gel (ME-G) containing AP in solubilized form. In an ex vivo skin absorption study using the Franz diffusion cell mounted on porcine skin, NS-G exhibited faster absorption in skin, providing approximately 4, 3, and 1.4 times larger accumulation than that of ME-G at 3, 6, and 12 h, respectively. Therefore, the high-payload NS makes it a promising platform for skin delivery of the lipid derivative of ascorbic acid.

Case Report: Successful Treatment of Recurrent Candida Albicans Meningitis with Kimura's Disease Using Amphotericin B Colloidal Dispersion Combined with Fluconazole.

Background: Candida albicans meningitis is a fungal infectious disease of the central nervous system that most often occurs in immunodeficient populations. Kimura's disease is an IgE-mediated inflammatory reactive disease that is a chronic immune disorder with predominantly lymph node, soft tissue, and salivary gland damage, the treatment of which is hormone-based. The combination of Kimura's disease with C. albicans meningitis is relatively uncommon. Herein, we report a case of C. albicans meningitis in combination with Kimura's disease. Case Presentation: The case is a 26-year-old male with a medical history of Kimura, who presented with symptoms of dizziness, headache, and double vision. Lumbar puncture and cerebrospinal fluid examination revealed an increased white blood cell count. Further analysis through cerebrospinal fluid culture and metagenomic second-generation sequencing (mNGS) led to the final diagnosis of C. albicans meningitis. The patient was treated with fluconazole after the onset of C. albicans meningitis and had a good response. During the treatment, changes in the pathogen genome sequences were monitored dynamically using metagenomic next-generation sequencing. After 1 year, the patient had a recurrence of Candida meningitis. Treatment with fluconazole alone was ineffective, while antifungal treatment with amphotericin B colloidal dispersion was effective with no detectable renal injury. Conclusion: Candida meningitis can occur in the context of Kimura disease. In patients with mild disease, the possibility of recurrence exists with fluconazole treatment alone, and the efficacy of amphotericin B colloidal dispersion combined with fluconazole is better than fluconazole alone in patients with a recurrence. No nephrotoxicity was observed during amphotericin B colloidal dispersion treatment. The mNGS allows dynamic monitoring of pathogen sequencing reads, and for Candida meningitis, there may be a mismatch between peak sequencing reads and disease during treatment, the basis for which is unclear.

A rapid, high-yield and bioinspired synthesis of colloidal silver nanoparticles using Glycyrrhiza glabra root extract and assessment of antibacterial and phytostimulatory activity.

Silver nanoparticles (AgNPs) have emerged as highly effective antimicrobial agents against multidrug-resistant (MDR) pathogens. This study aims to employ green chemistry principles for AgNP synthesis involving phytochemical-rich extract from Glycyrrhiza glabra roots. The approach highlights using renewable feedstocks, safer chemicals, minimum byproducts, and process scale-up. The synthesis of AgNPs was assessed using a surface plasmon resonance band at 420 nm, and structural properties were characterized using TEM, x-ray diffraction, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy. This method enables the production of high-yield dispersions of AgNPs with desired physicochemical characteristics, including dark yellow solution, size (~20 nm), spherical to an oval shape, crystal structure, and stable colloidal properties. The antimicrobial activity of AgNPs was investigated against the MDR bacteria strains of gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli). This work reveals that the antimicrobial activity of AgNPs can be influenced by bacterial cell wall components. The results demonstrate the strong interaction between AgNPs and E. coli, exhibiting a dose-dependent antibacterial response. The green approach facilitated the safer, facile, and rapid synthesis of colloidal dispersions of AgNPs, providing a sustainable and promising alternative to conventional chemical and physical methods. Furthermore, the effect of AgNPs on various growth parameters, including seed germination, root and shoot elongation, and dry weight biomass, was assessed for mung bean seedlings. The results revealed phytostimulatory effects, suggesting the promising prospects of AgNPs in the nano-priming of agronomic seeds. RESEARCH HIGHLIGHTS: Glycyrrhiza glabra root extract enabled rapid, high-yield, and eco-friendly synthesis of silver nanoparticles (AgNPs). Spectrophotometric analysis examined the optical properties, scalability, and stability of AgNPs. Transmission electron microscopy provided insights into the size, shape, and dispersity of AgNPs. Scanning electron microscopy revealed significant damage to gram-negative bacterial cell morphology and membrane integrity. AgNPs were found to enhance seed germination, seedling growth, and biomass yield of Vigna radiata.

Amphotericin B colloidal dispersion: an effective drug for the treatment of mucormycosis in China.

Objective: Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but the effective drugs for the treatment are limited. Hence, the study aimed to summarize the characteristics of mucormycosis in patients with hematological malignancies, and investigate the efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) in treating mucormycosis. Methods: In this study, patients with mucormycosis complicated by hematological malignancies who received ABCD at the First Affiliated Hospital of Zhengzhou University from April 2021 to May 2022 were retrospectively enrolled. The clinical data of the enrolled patients were collected, and then, the drug response at 2 weeks, 4 weeks, and the end of treatment; the survival rate at 4, 8, and 12 weeks; and the laboratory-related indicators and adverse events (AEs) associated with ABCD were evaluated. Results: In total, 9 patients with mucormycosis complicated by hematological malignancies were enrolled. The main symptoms were fever, cough, and chest pain. In addition, reversed halo signs (RHS) were found on chest CTs. The responses to ABCD at 2 weeks, 4 weeks, and the end of treatment were 100% (9/9), 77.8% (7/9), and 77.8% (7/9), respectively. The survival rates of the patients at 4, 8, and 12 weeks were 77.8% (7/9), 66.7% (6/9), and 66.7% (6/9), respectively. Among laboratory-related indicators, white blood cell (WBC) counts were significantly increased from baseline after 1 and 2 weeks of ABCD treatment (P<0.05), whereas neutrophil counts were only increased significantly from baseline at 2 weeks post-treatment (P<0.05). The most common AEs were infusion-related AEs manifesting as fever, chills, and pruritus. Moreover, none of the patients suffered from renal injury once again. Conclusion: ABCD is a promising treatment strategy for patients with mucormycosis complicated by hematologic malignancies, showing remarkable efficacy and safety.

Long-term water sorption/solubility of two dental bonding agents containing a colloidal dispersion of titanium dioxide.

The aim was to analyze the influence of the incorporation of 4% by mass of colloidal dispersion of titanium dioxide (TiO2) nanoparticles on the long-term water sorption and solubility of two commercial universal bonding agents. In vitro studies. A colloidal dispersion of TiO2 nanoparticles was formulated and blended into two commercial dental bonding agents, i.e., Ambar Universal (FGM, Brasil) and G-Premio Bond Universal (GC, America) at 4% by mass. Forty bonding agent discs were fabricated and segregated into four bonding agent groups of 10 discs each, i.e., GA: Ambar Universal (control), GB: Ambar Universal (4% TiO2 incorporated), GC: G-Premio Bond universal (control), and GD: G-Premio Bond (4% TiO2 incorporated). The bonding agent discs were developed by dispensing the bonding agents into a silicone cast of 5 mm diameter and 1 mm depth. After bonding agent discs were desiccated, the cured discs were weighed and kept in distilled water to be evaluated for water sorption and solubility over 1 year storage period. Statistical analysis was performed by independent variable t-test performed using the IBM SPSS software (Chicago, IL: SPSS Inc). The incorporated bonding agent groups (GA and GB) showed significantly lower (P < 0.05) water sorption and solubility following 1 year of water storage in comparison to the control bonding agents. Both GC and GD demonstrated remarkably lower water sorption and solubility than GA and GB. Incorporation of the colloidal dispersion of TiO2 nanoparticles at 4% by mass into the universal bonding agents has significantly reduced their water sorption and solubility contrast to their control groups.

Lyotropic Boron Nitride Nanotube Liquid Crystals: Preparation, Characterization, and Wet-Spinning for Fabrication of Composite Fiber.

Microfiber fabrication via wet-spinning of lyotropic liquid crystals (LCs) with anisotropic nanomaterials has gained increased attention due to the microfibers' excellent physical/chemical properties originating from the unidirectional alignment of anisotropic nanomaterials along the fiber axis with high packing density. For wet-spinning of the microfibers, however, preparing lyotropic LCs by achieving high colloidal stability of anisotropic nanomaterials, even at high concentrations, has been a critically unmet prerequisite, especially for recently emerging nanomaterials. Here, we propose a cationically charged polymeric stabilizer that can efficiently be adsorbed on the surface of boron nitride nanotubes (BNNTs), which provide steric hindrance in combination with Coulombic repulsion leading to high colloidal stability of BNNTs up to 22 wt %. The BNNT LCs prepared from the dispersions with various stabilizers were systematically compared using optical and rheological analysis to optimize the phase behavior and rheological properties for wet-spinning of the BNNT LCs. Systematic optical and mechanical characterizations of the BNNT microfibers with aligned BNNTs along the fiber axis revealed that properties of the microfibers, such as their tensile strength, packing density, and degree of BNNT alignment, were highly dependent on the quality of BNNT LCs directly related to the types of stabilizers.

Review on Different Vesicular Drug Delivery Systems (VDDSs) and Their Applications.

BACKGROUND: Colloidal dispersions, also known as vesicular drug delivery systems (VDDSs), are highly ordered assemblies composed of one or more concentric bilayers formed by the self-assembly of amphiphilic building blocks in the presence of water. OBJECTIVE: VDDSs are important to target the entrapped drugs at specific sites inside the body, control the drug release, enhance the drug bioavailability, and reduce undesired side effects. METHODS: There are different types of VDDSs suitable for the entrapment of both hydrophilic and lipophilic drugs. According to the patent composition, VDDSs are classified into lipid-based and nonlipid- based VDDSs. RESULTS: There are different types of VDDSs which include liposomes, ethosomes, transferosomes, ufasomes, colloidosomes, cubosomes, niosomes, bilosomes, aquasomes, etc. Conclusion: This review article aims to address the different types of VDDSs, their advantages and disadvantages, and their therapeutic applications.

Fungal Endophthalmitis in a Case of Rhino-Orbito-Cerebral Mucormycosis: Successfully Treated With Amphotericin B Colloidal Dispersion.

Background: Rhino-orbito-cerebral mucormycosis (ROCM) is an acute, fulminant, opportunistic fungal infection that usually occurs in diabetes or immunocompromised patients. Amphotericin B combined with surgical debridement remains the standard treatment, although it is controversial due to its lager nephrotoxicity. Thus far, no studies have reported the treatment for ROCM-associated fungal endophthalmitis because the exact pathogenesis and transmission routes in ROCM remain unclear. Here, we reported a case of ROCM complicated with fungal endophthalmitis treated favorably with amphotericin B colloidal dispersion (ABCD) in combination with other antifungals and surgical debridement. Case Presentation: A 34-year-old woman with diabetes was admitted to our hospital owing to right-sided headache for 8 days, blindness with swelling in the right eye for 5 days, and blindness in the left eye for 1 day. MRI showed that the patient had sphenoid sinus, sinuses, frontal lobe lesions, and proptosis of the right eye. Metagenomic sequencing revealed that the patient had Rhizopus oryzae infection. During hospitalization, the patient received intravenous ABCD, oral posaconazole, and topical amphotericin B and underwent surgical debridement. After 67 days of treatment, the patient's condition was significantly improved, and limb muscle strength showed grade V. Rhizopus oryzae showed negative results, and conjunctival swelling decreased. Additionally, no nephrotoxicity occurred during treatment. After discharge, the patient's treatment was transitioned to oral posaconazole and she was free of complaints during the 30-day follow-up without any additional treatment for ROCM. Conclusion: Treatment with ABCD combined with other antifungal drugs and surgical debridement for ROCM complicated with fungal endophthalmitis showed remarkable efficacy and good safety. Hence, this regimen is a promising treatment strategy for this fatal disease.

The Influence of Solvents and Colloidal Particles on the Efficiency of Molecular Antioxidants.

The radical scavenging activity of three molecular antioxidants (trolox, rutin and ellagic acid) was investigated in different solvents with and without added polymer-based colloidal particles (SL-IP-2). Rutin and ellagic acid showed poor solubility in water, preventing the accurate measurement of the effective antioxidant concentration values, which were determined in ethanol/water (EtOH/H2O) mixtures. The presence of trolox and rutin changed neither the surface charge properties nor the size of SL-IP-2 in these solvents, while significant adsorption on SL-IP-2 was observed for ellagic acid leading to overcharging and rapid particle aggregation at appropriately high antioxidant concentrations in EtOH/H2O. The differences in the radical scavenging capacity of trolox and ellagic acid that was observed in homogeneous solutions using water or EtOH/H2O as solvents vanished in the presence of the particles. Rutin lost its activity after addition of SL-IP-2 due to the larger molecular size and lower exposure of the functional groups to the substrate upon interaction with the particles. The obtained results shed light on the importance of the type of solvent and particle-antioxidant interfacial effects on the radical decomposition ability of molecular antioxidants, which is of crucial importance in industrial processes involving heterogeneous systems.

Use of casein micelles to improve the solubility of hydrophobic pea proteins in aqueous solutions via low-temperature homogenization.

The dairy industry struggles to maintain consumer attention in the midst of declining fluid milk sales. Current trends create an opportunity to incorporate plant-based proteins with milk to produce a high-protein, multisourced, functional food product. Plant-based proteins, such as those in peas, can be challenging to use in food systems because of their low solubility and undesirable off-flavors. Casein micelles have unique structural properties that allow for interactions with small ions and larger macromolecules that aid in their noteworthy ability as a nanovehicle for hydrophobic compounds. The objective of this study was to use the inherent structure of the casein micelle along with common dairy processing equipment to create a stable colloidal dispersion of casein micelles with pea protein to improve its solubility in aqueous solutions. We created 3 blends with varying ratios of casein-to-pea protein (90:10, 80:20, 50:50). We subjected the mixtures to 3 cycles of homogenization using a bench-top GEA 2-stage homogenizer at 27,580 kPa maintained at 4°C, followed by pasteurization at 63°C for 30 min. The resulting blends were homogeneous liquids with increased stability due to the lack of protein precipitation. Further protein analysis by HPLC and AA sequencing revealed that vicilin, an insoluble storage protein, was the main pea protein incorporated within the casein micelle structure. These results supported our hypothesis that low-temperature homogenization can successfully be used to create a colloidal dispersion with increased stability, in which insoluble plant-based proteins may be incorporated with casein micelles in an aqueous solution. Additionally, 3-dimensional microscope images of the blends indicated a noticeable difference between the surface roughness upon addition of pea protein to the casein micelle matrix. This research highlights a promising application for other plant-based proteins to be used within the dairy industry to help drive future product innovation while also meeting current processing conditions and consumer demands.

Colloidal dispersion of poly(ionic liquid)/Cu composite particles for protective surface coating against SAR-CoV-2.

Herein, we report a waterproof anti-SARS-CoV-2 protective film prepared by spray-coating of an aqueous colloidal dispersion of poly(ionic liquid)/copper (PIL/Cu) composite nanoparticles onto a substrate. The PIL dispersion was prepared by suspension polymerization of 3-dodecyl-1-vinylimdiazolium bromide in water at 70°C. The copper acetate salt was added into the PIL nanoparticle dispersion and in situ reduced into copper nanoparticles anchoring onto the PIL nanoparticles. Despite being waterborne, the PIL in bulk is intrinsically insoluble in water and the formed coating is stable in water. The formed surface coating by PIL/copper composite nanoparticles was able to deactivate SARS-CoV-2 virions by 90.0% in 30 minutes and thus may effectively prevent the spread of SARS-CoV-2 through surface contact. This method may provide waterborne dispersions for a broad range of antivirus protective surface coatings for both outdoor and indoor applications.

Surface Functionalization of WS2 Nanosheets with Alkyl Chains for Enhancement of Dispersion Stability and Tribological Properties.

Tungsten disulfide (WS2) exhibits intriguing tribological properties and has been explored as an excellent lubricious material in thin-film and solid lubricants. However, the poor dispersibility of WS2 has been a major challenge for its utilization in liquid lubricant applications. Herein, a top-down integrated approach is presented to synthesize oxygenated WS2 (WS2-O) nanosheets via strong acid-mediated oxidation and ultrasound-assisted exfoliation. The ultrathin sheets of WS2-O, comprising 4-7 molecular lamellae, exhibit oxygen/hydroxyl functionalities. The organosilanes having variable surface-active leaving groups (chloro and ethoxy) are covalently grafted, targeting the hydroxyl/oxygen functionalities on the surface of WS2-O nanosheets. The grafting of organosilanes is governed by the reactivity of chloro and ethoxy leaving groups. The DFT calculations further support the covalent interaction between the WS2-O nanosheets and organosilanes. The alkyl chain-functionalized WS2-O nanosheets displayed excellent dispersibility in mineral lube base oil. A minute dose of chemically functionalized-WS2 (0.2 mg.mL-1) notably enhanced the tribological properties of mineral lube oil by reducing the friction coefficient (52%) and wear volume (79%) for a steel tribopair. Raman analysis of worn surfaces revealed WS2-derived lubricious thin film formation. The improved tribological properties are attributed to ultralow thickness, stable dispersion, and low shear strength of chemically functionalized WS2 nanosheets, along with protective thin film formation over the contact interfaces of a steel tribopair. The present work opens a new avenue toward exploiting low-dimensional nanosheets for minimizing energy losses due to high friction.

Metronomic delivery of orally available pemetrexed-incorporated colloidal dispersions for boosting tumor-specific immunity.

In this study, we developed oral pemetrexed (PMX) for metronomic dosing to enhance antitumor immunity. PMX was electrostatically complexed with positively charged lysine-linked deoxycholic acid (DL) as an intestinal permeation enhancer, forming PMX/DL, to enhance its intestinal permeability. PMX/DL was also incorporated into a colloidal dispersion (CD) comprised of the block copolymer of poly(ethylene oxide) and poly(propylene oxide), and caprylocaproyl macrogol-8 glycerides (PMX/DL-CD). CD-containing PMX/DL complex in a 1:1 molar ratio [PMX/DL(1:1)-CD] showed 4.66- and 7.19-fold greater permeability than free PMX through the Caco-2 cell monolayer and rat intestine, respectively. This resulted in a 282% improvement in oral bioavailability in rats. In addition, low-dose metronomic PMX led to more immunogenic cell death in CT26.CL25 cells compared to high PMX concentrations at the maximum tolerated dose. In CT26.CL25 tumor-bearing mice, oral metronomic PMX/DL-CD elicited greater antitumor immunity not only by enhancing the number of tumor-infiltrating lymphocytes but also by suppressing T cell functions. Oral PMX/DL-CD substantially increased programmed cell death protein ligand-1 (PD-L1) expression on tumor cells compared to the control and PMX-IV groups. This increased antitumor efficacy in combination with anti-programmed cell death protein-1 (aPD-1) antibody in terms of tumor rejection and immunological memory compared to the combination of PMX-IV and aPD-1. These results suggest that oral metronomic scheduling of PMX/DL-CD in combination with immunotherapy has synergistic antitumor effects.

Pharmacokinetics and Safety of Single-Dose Amphotericin B Colloidal Dispersion in Healthy Chinese Subjects and Population Pharmacokinetic/Pharmacodynamic Analysis to Inform Clinical Efficacy in Invasive Infections Caused by Candida albicans.

PURPOSE: Amphotericin B colloidal dispersion (ABCD) is a less toxic formulation of amphotericin B for the treatment of invasive fungal infections. The pharmacokinetic (PK) profile and safety of a generic ABCD were investigated after a single dose (0.5 to 1.5 mg/kg) administered as an intravenous infusion in 30 healthy Chinese subjects. METHODS: PK data from healthy Chinese male subjects were applied for developing a population PK model to predict the PK profiles of standard doses (3 or 4 mg/kg) in patients. A 5000-time Monte Carlo simulation of AUC0-24/MIC target was implemented to determine the probability of target attainment (PTA) and cumulative fraction of response (CFR) under standard doses. FINDINGS: The PK profiles of intravenous administration of ABCD were best described by a 3-compartmental model with a time-varying clearance and a dose-dependent volume of distribution in the peripheral compartment. PK/pharmacodynamic (PK/PD) analysis revealed that 3 or 4 mg/kg ABCD once a day resulted in favorable CRF (>98%) with 2-log reduction of Candida albicans. A high PTA (>90%) was achieved at MIC ≤2 mg/L for the dosing regimen of ABCD 3 mg/kg and 4 mg/kg for MIC ≤4 mg/L. IMPLICATIONS: PK/PD analysis indicated that a favorable efficacy of ABCD could be reached at a dose of 3 or 4 mg/kg once daily for 14 to 28 days to treat invasive fungal infections caused by C albicans. ClinicalTrials.gov identifier: NCT03577509.

Delivery strategies of amphotericin B for invasive fungal infections.

Invasive fungal infections (IFIs) represent a growing public concern for clinicians to manage in many medical settings, with substantial associated morbidities and mortalities. Among many current therapeutic options for the treatment of IFIs, amphotericin B (AmB) is the most frequently used drug. AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance. In this review, we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs. We have also discussed the mechanism of actions of AmB, rationale for treating IFIs, and recent advances in formulating AmB for clinical use. Finally, this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.

Molecular Functionalization of 2H-Phase MoS2 Nanosheets via an Electrolytic Route for Enhanced Catalytic Performance.

The molecular functionalization of two-dimensional MoS2 is of practical relevance with a view to, for example, facilitating its liquid-phase processing or enhancing its performance in target applications. While derivatization of metallic 1T-phase MoS2 nanosheets has been relatively well studied, progress involving their thermodynamically stable, 2H-phase counterpart has been more limited due to the lower chemical reactivity of the latter. Here, we report a simple electrolytic strategy to functionalize 2H-phase MoS2 nanosheets with molecular groups derived from organoiodides. Upon cathodic treatment of a pre-expanded MoS2 crystal in an electrolyte containing the organoiodide, water-dispersible nanosheets derivatized with acetic acid or aniline moieties (∼0.10 molecular groups inserted per surface sulfur atom) were obtained. Analysis of the functionalization process indicated it to be enabled by the external supply of electrons from the cathodic potential, although they could also be sourced from a proper reducing agent, as well as by the presence of intrinsic defects in the 2H-phase MoS2 lattice (e.g., sulfur vacancies), where the molecular groups can bind. The acetic acid-functionalized nanosheets were tested as a non-noble metal-based catalyst for nitroarene and organic dye reduction, which is of practical utility in environmental remediation and chemical synthesis, and exhibited a markedly enhanced activity, surpassing that of other (1T- or 2H-phase) MoS2 materials and most non-noble metal catalysts previously reported for this application. The reduction kinetics (reaction order) was seen to correlate with the net electric charge of the nitroarene/dye molecules, which was ascribed to the distinct abilities of the latter to diffuse to the catalyst surface. The functionalized MoS2 catalyst also worked efficiently at realistic (i.e., high) reactant concentrations, as well as with binary and ternary mixtures of the reactants, and could be immobilized on a polymeric scaffold to expedite its manipulation and reuse.

Multidomain drug delivery systems of ß-casein micelles for the local oral co-administration of antiretroviral combinations.

The antiretroviral (ARV) cocktailrevolved the treatment of the human immunodeficiency virus (HIV) infection. Drug combinations have been also tested to treat other infectious diseases, including the recentcoronavirus disease 2019 (COVID-19) outbreak. To simplify administration fixed-dose combinationshave been introduced, however, oral anti-HIV therapy still struggles with low oral bioavailability of many ARVs.This work investigated the co-encapsulation of two clinically relevant ARV combinations,tipranavir (TPV):efavirenz (EFV) anddarunavir (DRV):efavirenz (EFV):ritonavir (RTV),within the core of ß-casein (bCN) micelles. Encapsulation efficiency in both systems was ~100%. Cryo-transmission electron microscopy and dynamic light scattering of the ARV-loaded colloidaldispersions indicatefull preservation of the spherical morphology, and x-ray diffraction confirm that the encapsulated drugs are amorphous. To prolong the physicochemical stabilitythe formulations were freeze-driedwithout cryo/lyoprotectant, and successfully redispersed, with minor changes in morphology.Then, theARV-loaded micelles were encapsulated within microparticles of Eudragit® L100, which prevented enzymatic degradation and minimized drug release under gastric-like pH conditionsin vitro. At intestinal pH, the coating polymer dissolved and released the nanocarriers and content. Overall, our results confirm the promise of this flexible and modular technology platform for oral delivery of fixed dose combinations.