Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system.

Silk fibroin nanoparticles (FNP) have been increasingly investigated in biomedical fields due to their biocompatibility and biodegradability properties. To widen the FNP versatility and applications, and to control the drug release from the FNP, this study developed the Eudragit S100-functionalized FNP (ES100-FNP) as a pH-responsive drug delivery system, by two distinct methods of co-condensation and adsorption, employing the zwitterionic furosemide as a model drug. The particles were characterized by sizes and zeta potentials (DLS method), morphology (electron microscopy), drug entrapment efficiency and release profiles (UV-Vis spectroscopy), and chemical structures (FT-IR, XRD, and DSC). The ES100-FNP possessed nano-sizes of ∼200-350 nm, zeta potentials of ∼ -20 mV, silk-II structures, enhanced thermo-stability, non-cytotoxic to the erythrocytes, and drug entrapment efficiencies of 30%-60%, dependent on the formulation processes. Interestingly, the co-condensation method yielded the smooth spherical particles, whereas the adsorption method resulted in durian-shaped ones due to furosemide re-crystallization. The ES100-FNP adsorbed furosemide via physical adsorption, followed Langmuir model and pseudo-second-order kinetics. In the simulated oral condition, the particles could protect the drug in the stomach (pH 1.2), and gradually released the drug in the intestine (pH 6.8). Remarkably, in different pH conditions of 6.8, 9.5, and 12, the ES100-FNP could control the furosemide release rates depending on the formulation methods. The ES100-FNP made by the co-condensation method was mainly controlled by the swelling and corrosion process of ES100, and followed the Korsmeyer-Peppas non-Fickian transport mechanism. Whereas, the ES100-FNP made by the adsorption method showed constant release rates, followed the zero-order kinetics, due to the gradual furosemide dissolution in the media. Conclusively, the ES100-FNP demonstrated high versatility as a pH-responsive drug delivery system for biomedical applications.

Silk fibroin hydrogel containing Sesbania sesban L. extract for rheumatoid arthritis treatment.

PURPOSE: Rheumatoid arthritis, a chronic and progressive inflammation condition in the joints, has significantly reduced the patient quality of life and life expectancy. Crucially, there is no complete therapy for this disease, and the current treatments possess numerous side effects. Thus, novel therapeutic approach is necessary. To that end, this study developed novel silk fibroin in-situ hydrogel containing Sesbania sesban L. extract, a plant with high anti-inflammatory actions that are beneficial for rheumatoid arthritis treatments. METHODS: The hydrogels were manufactured using simple method of spontaneous gelation at different temperature. The gel properties of morphology, gelation time, viscosity, gel strength, stability, drug loading capacity, drug release rate, and in-vitro anti-inflammatory activity were investigated with appropriate methods. RESULTS: The optimal formulation had highly porous structure, with a gelation time of 0.5 h at room temperature and bodily temperature of 37 °C, a viscosity of 2530 ± 50 cP, a gel strength of 1880.14 ± 35.10 g, and a physical stability of >6 months. Moreover, the hydrogel contained the Sesbania sesban L. leaf extract with a total phenolic content of 92.8 ± 8.30 mg GAE/g, and sustained the release rate for >20 days, followed the Higuchi model. Regarding the in-vitro activities, all formulations were nontoxic to the RAW 264.7 cell line and demonstrated comparable anti-inflammatory activity to the free extract, in terms of the NO reduction levels. CONCLUSION: Conclusively, the systems possessed potential properties to be further investigated to become a prospective rheumatoid arthritis treatment.

Dysfunction of lipid storage droplet-2 suppresses endoreplication and induces JNK pathway-mediated apoptotic cell death in Drosophila salivary glands.

The lipid storage droplet-2 (LSD-2) protein of Drosophila is a homolog of mammalian perilipin 2, which is essential for promoting lipid accumulation and lipid droplet formation. The function of LSD-2 as a regulator of lipolysis has also been demonstrated. However, other LSD-2 functions remain unclear. To investigate the role of LSD-2, we performed tissue-specific depletion in the salivary glands of Drosophila using a combination of the Gal4-upstream activating sequence system and RNA interference. LSD-2 depletion inhibited the entry of salivary gland cells into the endoreplication cycle and delayed this process by enhancing CycE expression, disrupting the development of this organ. The deficiency of LSD-2 expression enhanced reactive oxygen species production in the salivary gland and promoted JNK-dependent apoptosis by suppressing dMyc expression. This phenomenon did not result from lipolysis. Therefore, LSD-2 is vital for endoreplication cell cycle and cell death programs.

Effects of Launaea sarmentosa Extract on Lipopolysaccharide-Induced Inflammation via Suppression of NF-κB/MAPK Signaling and Nrf2 Activation.

Launaea sarmentosa has been extensively used as a nutrient herb in traditional Vietnamese remedies for the treatment of various diseases, especially inflammatory diseases. However, no detailed research has been conducted examining the molecular mechanisms involved in the suppression of inflammatory response. Here, we studied the effects of L. sarmentosa methanol extract on lipopolysaccharide (LPS)-induced inflammation using RAW 264.7 macrophages. The extract demonstrated potent antioxidant activity owing to the presence of polyphenolic and flavonoid components. Pretreatment with the extract inhibited LPS-mediated secretion of nitric oxide, reactive oxygen species, and tumor necrosis factor-α as well as the expression of inflammatory cytokines. Furthermore, the activation of the nuclear factor-kappa B pathway and phosphoinositide-3-kinase/protein kinase B pathways was blocked by the extract by inhibiting Akt phosphorylation. Additionally, the mitogen-activated protein kinase pathway was suppressed, and endoplasmic reticulum stress was attenuated. Furthermore, the extract promoted the activity of nuclear factor erythroid-2-related factor 2 resulting in the up-regulation of heme oxygenase-1 pathway, leading to the suppression of oxidative stress and inflammatory response. Taken together, the results indicate that L. sarmentosa exhibits anti-inflammatory effects, and hence, can be further developed as a novel drug for the treatment of diseases associated with excessive inflammation.

Role of Serotonin Transporter in Eye Development of Drosophila melanogaster.

Serotonin transporter (SerT) in the brain is an important neurotransmitter transporter involved in mental health. However, its role in peripheral organs is poorly understood. In this study, we investigated the function of SerT in the development of the compound eye in Drosophila melanogaster. We found that SerT knockdown led to excessive cell death and an increased number of cells in S-phase in the posterior eye imaginal disc. Furthermore, the knockdown of SerT in the eye disc suppressed the activation of Akt, and the introduction of PI3K effectively rescued this phenotype. These results suggested that SerT plays a role in the healthy eye development of D. melanogaster by controlling cell death through the regulation of the PI3K/Akt pathway.

Anti-Inflammatory Effects of Lasia spinosa Leaf Extract in Lipopolysaccharide-Induced RAW 264.7 Macrophages.

Lasia spinosa (L.) Thwaites was used as a traditional medicine to treat many inflammatory diseases for centuries. However, its effects on the inflammatory response are not yet characterized. In this study, we investigated the anti-inflammatory activities of L. spinosa leaf extract in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. We found that ethanol extracts of L. spinosa leaves showed anti-oxidant activity due to the presence of high levels of polyphenolic compounds. Treatment with the leaf extract significantly repressed the production of inflammatory mediators such as nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines in the LPS-stimulated RAW 264.7 cells. Moreover, L. spinosa leaf extract treatment prevented activation of the nuclear factor-kappa B pathway by inhibiting nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) degradation. Furthermore, the mitogen-activated kinase and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways were suppressed upon treatment with the leaf extract. In addition to suppressing inflammatory factors, the extract also activated the nuclear factor erythroid 2-related factor 2/heme-oxygenase-1 pathway. We propose that L. spinosa leaf extract has the potential as an effective therapeutic agent for alleviating oxidative stress and excessive inflammation.