Presence of humic acid in the environment holds promise as a potential mitigating factor for the joint toxicity of polystyrene nanoplastics and herbicide atrazine to Chlorella vulgaris: 96-H acute toxicity.

Increasing amounts of amino-functionalized polystyrene nanoplastics (PS-NH2) are entering aquatic ecosystems, raising concerns. Hence, this study investigated 96-h acute toxicity of PS-NH2 and its combination with the pesticide atrazine (ATZ) in the absence/presence of humic acid (HA) on the microalgae Chlorella vulgaris (C. vulgaris). Results showed that both PS-NH2 and PS-NH2+ATZ reduced algal growth, photosynthetic pigments, protein content, and antioxidant capacity, while increasing enzymatic activities. Gene expression related to oxidative stress was altered in C. vulgaris exposed to these treatments. Morphological and intracellular changes were also observed. The combined toxicity of PS-NH2+ATZ demonstrated a synergistic effect, but the addition of environmentally relevant concentration of HA significantly alleviated its toxicity to C. vulgaris, indicating an antagonistic effect due to the emergence of an eco-corona, and entrapment and sedimentation of PS-NH2+ATZ particles by HA. This study firstly highlights the role of HA in mitigating the toxicity of PS-NH2 when combined with other harmful compounds, enhancing our understanding of HA's presence in the environment.

Alleviating binary toxicity of polystyrene nanoplastics and atrazine to Chlorella vulgaris through humic acid interaction: Long-term toxicity using environmentally relevant concentrations.

In this study, microalgae Chlorella vulgaris (C. vulgaris) were simultaneously exposed to environmental concentrations of amino-functionalized polystyrene nanoplastics (PS-NH2; 0.05, 0.1, 0.2, 0.3 and 0.4 mg/L) and the world's second most used pesticide, the herbicide atrazine (ATZ; 10 µg/L), in the absence and presence of humic acid (HA; 1 mg/L) for 21 days. Due to the low concentrations of PS-NH2, the majority of them could not cause a significant difference in the end-points of biomass, chlorophylls a and b, total antioxidant, total protein, and superoxide dismutase and malondialdehyde compared to the control group (p > 0.05). On the other hand, by adding ATZ to the PS-NH2, all the mentioned end-point values showed a considerable difference from the control (p < 0.05). The exposure of PS-NH2+ATZ treatments to the HA could remarkably reduce their toxicity, additionally, HA was able to decrease the changes in the expression of genes related to oxidative stress (e.g., superoxide dismutase, glutathione reductase, and catalase) in the C. vulgaris in the most toxic treatment group (e.g., PS-NH2+ATZ). The synergistic toxicity of the PS-NH2+ATZ group could be due to their enhanced bioavailability for algal cells. Nevertheless, the toxicity alleviation in the PS-NH2+ATZ treatment group after the addition of HA could be due to the eco-corona formation, and changes in their zeta potential from positive to negative value, which would increase their electrostatic repulsion with the C. vulgaris cells, in such a way that HA also caused a decrease in the formation of C. vulgaris-NPs hetero-aggregates. This research underscores the complex interplay between PS-NH2, ATZ, and HA in aquatic environments and their collective impact on microalgal communities.

Discovery of the Effects of the Hemiprotonic Phenanthroline-Phenanthroline+ against Trichophyton rubrum by Inducing Fungal Apoptosis.

Trichophyton rubrum (T. rubrum) is the most common causative agent of dermatophytosis worldwide. The development of antifungal drugs will contribute to treating the disease. In this study, we suggest that a hemiprotonic compound phenanthroline-phenanthroline+ (ph-ph+) is active in inhibiting the growth and reproduction of T. rubrum, and the minimum inhibitory concentration and minimum fungicidal concentration values were 2 µg/ml and 8 µg/ml, respectively. In an in vitro onychomycosis model, ph-ph+ killed T. rubrum by inducing apoptosis, which was evaluated by transmission electron microscopy and Annexin V-FITC/propidium iodide staining. Transcriptomic analysis and biochemical assay showed that ph-ph+ elevated iron ion content in T. rubrum cells and reduced glutathione antioxidant system level, leading to an increase in the contents of ROS and malondialdehyde. Therefore, the antifungal mechanism of ph-ph+ would be associated with iron ion-induced cell apoptosis, which is different from other known antifungal drugs. Furthermore, ph-ph+ was prepared into gel for application in guinea pigs with dermatophytosis caused by T. rubrum. The results showed that the ph-ph+ gel eliminated the fungus in the animals without causing skin irritation or other adverse reactions. The study would not only provide a potential compound to treat dermatophytosis, but also suggest that iron ion-induced cell apoptosis might be a new approach to killing fungi.

Quaternary enteric solid dispersion prepared by hot-melt extrusion to mask the bitter taste and enhance drug stability.

To mask the bitterness of drug is profoundly important especially in children's medication. This study designed and investigated a quaternary enteric solid dispersion (QESD) by secondary hot-melt-extrusion. Erythromycin (EM) was chosen as a model drug. The optimal QESD contained enteric polymer HPMCP-55, plasticizer and water-soluble polymer copovidone VA64. Raman and Atomic force microscope has exploited that majority EM was distributed in VA64 matrix, nanometer-sized EM-VA64 system was entrapped within enteric continuous phase to form a solid emulsion-like structure. For the prepared QESD, EM released concentration was far less than bitterness threshold (7 µg/mL to 20 µg/mL) in artificial saliva within the first 30 s. And dissolution rate was increased by 10% in article intestine fluid, which dominated by water-soluble VA64. Stress testing after two months at high-humidity (75% RH) and high-temperature (60 °C) revealed, compared with traditional enteric SDs, the chemical degradation of EM was slowed down in QESD. Furthermore, hydrogen and salt bonds were respectively formed between EM and VA64 and between leaking EM and HPMCP-55, which increasing the system stability and taste-masking. The effect of masking bitter taste can be satisfied as well as enhance drug dissolution rate in the intestine, and formulation physicochemical stability during storage.

Encapsulation of Azithromycin Ion Pair in Liposome for Enhancing Ocular Delivery and Therapeutic Efficacy on Dry Eye.

The aim of this work was to design a novel ocular delivery carrier based on liposomes loaded with azithromycin (AZM) for the treatment of dry eye (DE) disease. To improve the drug loading efficiency, an AZM-cholesteryl hemisuccinate (CHEMS) ion pair (ACIP) was first prepared, and the successful formation of the ACIP was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD), which demonstrated a stable interaction between CHEMS and AZM. The ACIP-loaded liposome (ACIP-Lip) appeared as spherical particles under TEM, with a uniform particle size of 60 ± 2 nm and zeta potential of -20.3 ± 4.6 mV. The entrapment efficiency (EE) and drug loading (DL) of ACIP-Lip were greatly improved to 95.6 ± 2.0 and 9.2 ± 0.7%, respectively, which was attributed to the enhanced loading capacity of the liposomes through use of the ion pair and addition of MCT. ACIP-Lip also exhibited a high stability during a 3 month storage period at both 4 and 25 °C. In vitro release of AZM from ACIP-Lip was pH-dependent, with a more rapid release at pH 6.0 than at pH 7.4, which is beneficial for ocular therapy. Furthermore, the corneal permeation of AZM was enhanced by ACIP-Lip, demonstrating an apparent permeability coefficient ( Papp × 106) of 8.92 ± 0.56 cm/s, which was approximately 2-fold greater that of the AZM solution. Finally, an in vivo pharmacodynamical study showed that the essential symptoms of DE rats were significantly improved by ACIP-Lip, as it was highly efficient and superior compared to hyaluronic acid sodium eye drops available on the market. Hence, ACIP-Lip is a promising formulation for DE treatment.