Pulmonary delivery of nintedanib has noticeable advantages over the current oral administration in managing idiopathic pulmonary fibrosis (IPF). However, it remains a challenge to construct an efficient lung delivery system for insoluble nintedanib to resist nebulization instabilities and alveolar macrophage clearance. Herein, we attempted to develop nintedanib as inhalable nanocrystals stabilized with polysorbates. Different types of polysorbates (polysorbate 20, 40, 60, 80) and various drug-surfactant molar ratios (DSR = 10, 30, 60) were screened to determine the optimal nintedanib nanocrystal formulation. Most formulations (except those stabilized by polysorbate 40) could tailor nintedanib nanocrystals with sizes around 600 nm, and the nebulization-caused drug loss could be significantly reduced when DSR increased to 60. Meanwhile, all nanocrystals boosted the in vitro drug dissolution rate and improved the aerosol performance of nintedanib. Although nebulization-caused particle aggregation was found in most formulations, the nanocrystal stabilized with polysorbate 80 at DSR 60 presented no apparent size change after nebulization. This formulation exhibited superior alveolar macrophage evasion, enhanced fibroblast cluster infiltration, and improved fibroblast cluster inhibition compared with other formulations, indicating its significant potential for pulmonary nintedanib delivery. Overall, this study explored the potential of polysorbates in stabilizing nintedanib nanocrystals for nebulization and proposed practical solutions to transfer nintedanib from oral to lung delivery.

The study investigates the effect of biotin concentration on the role of anaplerotic reactions catalysed by pyruvate carboxylase (PC) and phosphoenolpyruvate carboxylase (PEPC) in glutamic acid production by requires biotin for its growth, and its glutamic acid production can be induced by the addition of Tween 40 or penicillin or by biotin limitation. The biotin enzyme PC and the non-biotin enzyme PEPC catalyse two anaplerotic reactions to supply oxaloacetic acid to the TCA cycle in . Therefore, they are crucial for glutamic acid production in this bacterium. In this study, we investigated the contribution of each anaplerotic reaction to Tween 40- and penicillin-induced glutamic acid production using disruptants of PEPC and PC. In the presence of 20 µg l biotin, which is sufficient for growth, the PEPC-catalysed anaplerotic reaction mainly contributed to Tween 40- and penicillin-induced glutamic acid production. However, when increasing biotin concentration 10-fold (i.e. 200 µg l), both PC- and PEPC-catalysed reactions could function in glutamic acid production. Western blotting revealed that the amount of biotin-bound PC was reduced by the addition of Tween 40 and penicillin in the presence of 20 µg l. However, these induction treatments did not change the amount of biotin-bound PC in the presence of 200 µg l biotin. These results indicate that both anaplerotic reactions are functional during glutamic acid production in and that biotin concentration mainly affects which anaplerotic reactions function during glutamic acid production.

Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent development of biofilms within the wound area necessitates the identification of novel treatment strategies for use within infected chronic wounds. Here, several non-antibiotic compounds, polyhexamethylene biguanide (PHMB), curcumin, retinol, polysorbate 40, ethanol, and D-α-tocopheryl polyethylene glycol succinate 1000 (TPGS) were screened for their antibacterial and antibiofilm capabilities. The minimum inhibitory concentration (MIC) and crystal violet (CV) biofilm clearance against two bacteria frequently associated with infected chronic wounds, and , were determined. PHMB was observed to have highly effective antibacterial activity against both bacteria, but its ability to disperse biofilms at MIC levels was variable. Meanwhile, TPGS had limited inhibitory activity but demonstrated potent antibiofilm properties. The subsequent combination of these two compounds in a formulation resulted in a synergistic enhancement of their capability to kill both and and disperse their biofilms. Collectively, this work highlights the utility of combinatory approaches to the treatment of infected chronic wounds where bacterial colonization and biofilm formation remains significant issues.

The purpose of this work was to evaluate the possibility of adding tea saponin (TS) to reduce the synthetic surfactant concentration, and maintain or improve the shelf stability of nanoemulsions. The essential oil (2.5 wt%) loaded oil-in-water nanoemulsions were co-stabilized by Tween 40 (0.5-2.5 wt%) and TS (0.1-5 wt%). A combination of several analytical techniques, such as dynamic laser scattering, interfacial tension, zeta potential, and transmission electron microscope, were used for the characterization of nanoemulsions. Low levels of TS (0.1-0.5 wt%) with Tween 40 had significant effects on the emulsification, and a nanoemulsion with the smallest droplet diameter of 89.63 ± 0.67 nm was obtained. However, in the presence of high TS concentration (0.5-5 wt%), micelles generated by the non-adsorbed surfactants in the aqueous lead to droplets growth. In addition, the combinations of Tween 40 and TS at the high level (>3.5 wt%) exerted a synergistic effect on stabilizing the nanoemulsions and preventing both Ostwald ripening and coalescence. The negative charged TS endowed the droplets with electrostatic repulsion and steric hinderance appeared to prevent flocculation and coalescence. These results would provide a potential application of natural TS in the preparation and stabilization of nanoemulsions containing essential oil.

Growing evidence has shown that some pharmaceutical excipients can act on drug transporters. The present study was aimed at investigating the effects of 13 commonly used excipients on the intestinal absorption of metformin (MTF) and the underlying mechanisms using Caco-2 cells and an mouse non-everted gut sac model. First, the uptake of MTF in Caco-2 cells was markedly inhibited by nonionic excipients including Solutol HS 15, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, and crospovidone. Second, transport profile studies showed that MTF was taken up via multiple cation-selective transporters, among which a novel pyrilamine-sensitive proton-coupled organic cation (H/OC) antiporter played a key role. Third, Solutol HS 15, polysorbate 40, and polysorbate 60 showed -inhibitory effects on the uptake of either pyrilamine (prototypical substrate of the pyrilamine-sensitive H/OC antiporter) or 1-methyl-4-phenylpyridinium (substrate of traditional cation-selective transporters including OCTs, MATEs, PMAT, SERT, and THTR-2), indicating that their suppression on MTF uptake is due to the synergistic inhibition toward multiple influx transporters. Finally, the pH-dependent mouse intestinal absorption of MTF was significantly decreased by Solutol HS 15, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, and pyrilamine. In conclusion, this study revealed that a novel transport process mediated by the pyrilamine-sensitive H/OC antiporter contributes to the intestinal absorption of MTF in conjunction with the traditional cation-selective transporters. Mechanistic understanding of the interaction of excipients with cation-selective transporters can improve the formulation design and clinical application of cationic drugs.

In this study, the effects of Tween 40 and ethanol supplementation on the secretion, structure and antioxidant activities of exopolysaccharide (EPS) from Inonotus rickii were investigated. It was observed that Tween 40 and ethanol displayed a stimulatory effect on EPS secretion. The EPSs obtained by the addition of Tween 40 (EPS-T), ethanol (EPS-E) and control (EPS-C) were purified by Sepharose CL-6B gel chromatography and molecular weights of EPS-T, EPS-E and EPS-C were estimated to be 22.1, 30.0, and 40.5 kDa, respectively. Monosaccharide composition analysis indicated that EPS-T, EPS-E and EPS-C were mainly composed of mannose and glucose. Furthermore, EPS-E exhibited better OH• and DPPH scavenging activities than those of EPS-C and EPS-T, which might be associated with its molecular characterization.

L-ornithine is a valuable amino acid with a wide range of applications in the pharmaceutical and food industries. However, the production of L-ornithine by fermentation cannot compete with other methods, because of the low titers produced with this technique. Development of fermentation techniques that result in a high yield of L-ornithine and efficient strategies for improving L-ornithine production are essential.

Dispersants including Tween 20, Tween 40, Tween 60, and polyacrylic acid (PAA) were used to modify nanoscale zero-valent iron (nZVI). All dispersants dispersed nZVI effectively. PAA-modified nZVI was more stable than nZVI that was modified with Tween surfactant. Iron nanoparticles that were prepared using 0.5-5.0% (vol%) of PAA remained in suspension for more than 2 h. nZVI that was modified using Tween surfactant remained in suspension for 30-60 min, and there was complete sedimentation of bare iron in 10 min. When 2.0-5.0% (vol%) of Tween surfactant was used, the stability of the nZVI that was modified using Tween 20 was much better than that for nZVI that was modified using Tween 40 or Tween 60. The results for the transportation test show that nZVI that was prepared using 2% (vol%) of Tween 20 exhibited the best mobility in porous media. Approximately 83-90% of TCE was degraded by bare, PAA-modified, and Tween 20-modified nZVI, and about 63-67% of TCE was removed by nZVI that was modified using Tween 40 and Tween 60 during 20 days of reaction. The production of cis-dichloroethene (DCE) and 1,1-DCE demonstrates that TCE is removed via reductive dechlorination. The results of this study show that PAA- and Tween 20-modified nZVI are more practical for in situ remediation because they exhibit good mobility and degrade TCE effectively.

Understanding the bioactive partitioning between the phases of an emulsion system underpins strategies for improving the efficiency of bioactive protection against degradation. We analysed partitioning of β-carotene in emulsions with various formulations in-situ using confocal Raman microscopy (CRM). The partitioning of β-carotene into the aqueous phase of emulsions increased when whey protein isolate (WPI) was heat or high pressure-treated prior to emulsion formation. However, increasing the concentration of high pressure-treated WPI reduced the β-carotene partitioning into the aqueous phase. Increasing the solid fat content in the carrier oil favoured the migration of β-carotene into the aqueous phase. The use of WPI as the emulsifier resulted in a greater partitioning of β-carotene into the aqueous phase compared to when Tween 40 was the emulsifier. This study demonstrates that partitioning of β-carotene between the aqueous and oil phase is dependent on the characteristics of the oil phase, emulsifier type and processing.

Two O/W forskolin-loaded nano-emulsions (0.075% wt.) based on medium chain triglycerides (MCT) and stabilized by a nonionic surfactant (Polysorbate 80 or Polysorbate 40) were studied as forskolin delivery systems. The nano-emulsions were prepared by the PIC method. The mean droplet size of the nano-emulsions with Polysorbate 80 and Polysorbate 40 with oil/surfactant (O/S) ratios of 20/80 and 80% water concentration, measured by Dynamic Light Scattering (DLS), was of 118 nm and 111 nm, respectively. Stability of the formulations, as assessed by light backscattering for 24 h, showed that both nano-emulsions were stable at 25°C. Studies of forskolin in vitro skin permeation from the nano-emulsions and from a triglyceride solution were carried out at 32°C, using Franz-type diffusion cells. A mixture of PBS/ethanol (60/40 v/v) was used as a receptor solution. The highest flux and permeability coefficient was obtained for the system stabilized with Polysorbate 80 (6.91±0.75 µg · cm·h and 9.21 · 10±1.00 · 10 cm · h, respectively) but no significant differences were observed with the flux and permeability coefficient value of forskolin dissolved in oil. The obtained results showed that the nano-emulsions developed in this study could be used as effective carriers for topical administration of forskolin.