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Biopharmaceutical classification systems (BCS) class III drugs belongs to a group of drugs with high solubility in gastrointestinal (GI) fluids and low membrane permeability result in significantly low bioavailability. Self-emulsifying drug delivery systems (SEDDS) considered a suitable candidate to enhance the bioavailability of poorly soluble drugs by improving their membrane permeability, however, incorporating hydrophilic drugs in to these carriers remained a great challenge. The aim of this study was to develop hydrophobic ion pairs (HIPs) of a model BCS class-III drug tobramycin (TOB) in order to incorporate into SEDDS and improve its bioavailability. HIPs of TOB were formulated using anionic surfactants sodium docusate (DOC) and sodium dodecanoate (DOD). The efficiency of HIPs was estimated by measuring the concentration of formed complexes in water, zeta potential determination and log P value evaluation. Solubility studies of HIPs of TOB with DOC were accomplished to screen the suitable excipients for SEDDS development. Consequently, HIPs of TOB with DOC were loaded into SEDDS and assessed the log DSEDDS/release medium and dissociation of these complexes at different intestinal pH over time. Moreover, cytotoxic potential of HIPs of TOB and HIPs loaded SEDDS formulations was evaluated. HIPs of TOB with DOC exhibited the maximum precipitation efficiency at a stoichiometric ratio of 1:5. Log P of HIPs of TOB improved up to 1500-fold compared to free TOB. Zeta potential of TOB was shifted from positive to negative during hydrophobic ion pairing (HIP). HIPs of TOB with DOC was loaded at a concentration of 1% (w/v) into SEDDS formulations. Log DSEDDS/release medium of loaded complexes in to oily droplets was above 2 and dissociated up to 20% at various pH within 4 h. Finding of this study suggested that improvement of the lipophilic character of BCS class-III drugs followed by incorporation into oily droplets can be deliberated as a promising tool to enhance the permeation across biological membranes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Asad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The present work aimed to form hydrophobic ion pairs (HIPs) of a small molecule remaining inside the oily droplets of SEDDS to a high extent. HIPs of ethacridine and various surfactants classified by functional groups of phosphates, sulfates, and sulfonates were formed and precipitation efficiency, log D n -octanol/water , and solubility in different excipients were investigated. Most lipophilic HIPs were incorporated into SEDDS and evaluated regarding drug release. Docusate HIPs showed the highest increase in lipophilicity with a precipitation efficiency of 100%, a log D n -octanol/water of 2.66 and a solubility of 132 mg/mL in n -octanol, 123 mg/mL in oleyl alcohol, and 40 mg/mL in medium chain triglycerides. Docusate HIPs were incorporated into three SEDDS of increasing lipophilicity (F1 < F2 < F3) based on medium chain triglycerides, oleyl alcohol, Kolliphor EL, and Tween 80 (F1: 1 + 5 + 2 + 2; F2: 3 + 3 + 2 + 2; F3: 5 + 1 + 4 + 0). Highest achievable payloads ranged from 74.49 mg/mL (F3) to 97.13 mg/mL (F1) and log D SEDDS/RM increased by at least 7.5 units (4.99, F1). Drug release studies via the diffusion membrane method confirmed minor release of docusate HIPs from all SEDDS (<2.7% within 4 h). In conclusion, highly lipophilic HIPs remain inside the oily phase of SEDDS and likely reach the absorption membrane in intact form.

In many jurisdictions, dispersants are included in contingency plans as a viable countermeasure that can help reduce the overall environmental impact of marine oil spills. When used, it is imperative to monitor the progression of dispersant and oil to assess their environmental fate and behaviour. Amphiphilic salt dioctyl sodium sulfosuccinate (DOSS) is the major effective component of the most commonly available dispersants, such as Corexit® EC9500A. Without proper sample preparation, dispersed oil in water samples could interfere with the accurate analysis of DOSS and easily contaminate the LC-MS system. In this work, solid phase extraction (SPE) weak anion exchange (WAX) cartridges were used to separate oil and DOSS in aqueous samples. DOSS was accurately determined by liquid chromatography coupled with a high resolution Orbitrap mass spectrometer (LC-HRMS). Oil fingerprinting analysis was conducted and total petroleum hydrocarbons (TPHs), polycyclic aromatic hydrocarbons (PAHs), and petroleum biomarkers were determined by gas chromatography-flame ionization detection (GC-FID) and mass spectrometry (GC-MS). This SPE-LC/GC-MS method was used for the analysis of oil-dispersant water samples containing a mixture of Corexit® EC9500A and a selection of crude oils and refined petroleum products. Nearly a 100% DOSS recovery was obtained for various oil-surfactant conditions. Parallel quantitation of oils with dispersants was achieved using this method. A portion of the TPH loss was possibly attributed to oil retained by the SPE column. Chemical fingerprints and diagnostic ratios of target compounds in recovered dispersed oil overall remain unchanged compared with those of all studied oils., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Dioctyl Sodium Sulfosuccinate (DOSS, CAS 577-11-7) is a chemical emulsifying surfactant that is widely used in the food and the cosmetic industry, and it is also the major component of the crude oil chemical dispersant Corexit™. Despite of its wide use, the studies related to its negative effect have been evaluated mainly in marine environments showing that DOSS is highly bioactive, extremely low volatile, and potential to persist in the environment longer than other dispersant components. Up to date, there is no available information of DOSS concentration in freshwater environments, little is known about its downstream fate after excretion and its effect on freshwater organisms. The objective of this study was to evaluate the effect of DOSS at different concentrations in embryos and adults of zebrafish Danio rerio in an acute-static bioassays of 96 h. The median lethal concentration in embryos was 33.3 mg/L. Malformations started to be observed at 10 mg/L. In adults, the gene expression analysis in gill tissues showed a deregulation in genes associated with the antioxidant system and the nucleotide excision repair mechanism. Additionally, Micronuclei (DNA damage) in erythrocytes, and fat degeneration in liver, hypertrophy and hyperplasia in gills, and hyaline drops in kidney tissues were also observed. In conclusion, the concentrations of DOSS evaluated here would be of health relevance to fish based on morphological alterations in embryos and changes in the gene expression profile, DNA damage and tissue impairment in adults., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hydrophobic ion pairing is a promising strategy to raise the lipophilic character of therapeutic peptides and proteins. In past studies, docusate, an all-purpose surfactant with a dialkyl sulfosuccinate structure, showed highest potential as hydrophobic counterion. Being originally not purposed for hydrophobic ion pairing, it is likely still far away from the perfect counterion. Thus, within this study, docusate analogues with various linear and branched alkyl residues were synthesized to derive systematic insights into which hydrophobic tail is most advantageous for hydrophobic ion pairing, as well as to identify lead counterions that form complexes with superior hydrophobicity. The successful synthesis of the target compounds was confirmed by FT-IR, 1 H-NMR, and 13 C-NMR. In a screening with the model protein hemoglobin, monostearyl sulfosuccinate, dioleyl sulfosuccinate, and bis(isotridecyl) sulfosuccinate were identified as lead counterions. Their potential was further evaluated with the peptides and proteins vancomycin, insulin, and horseradish peroxidase. Dioleyl sulfosuccinate and bis(isotridecyl) sulfosuccinate significantly increased the hydrophobicity of the tested peptides and proteins determined as logP or lipophilicity determined as solubility in 1-octanol, respectively, in comparison to the gold standard docusate. Dioleyl sulfosuccinate provided an up to 8.3-fold higher partition coefficient and up to 26.5-fold higher solubility in 1-octanol than docusate, whereas bis(isotridecyl) sulfosuccinate resulted in an up to 6.7-fold improvement in the partition coefficient and up to 44.0-fold higher solubility in 1-octanol. The conjugation of highly lipophilic alkyl tails to the polar sulfosuccinate head group allows the design of promising counterions for hydrophobic ion pairing. STATEMENT OF SIGNIFICANCE: Hydrophobic ion pairing enables efficient incorporation of hydrophilic molecules into lipid-based formulations by forming complexes with hydrophobic counterions. Docusate, a sulfosuccinate with two branched alkyl tails, has shown highest potential as anionic hydrophobic counterion. As it was originally not purposed for hydrophobic ion pairing, its structure is likely still far away from the perfect counterion. To improve its properties, analogues of docusate with various alkyl tails were synthesized in the present study. The investigation of different alkyl residues allowed to derive systematic insights into which tail structures are most favorable for hydrophobic ion pairing. Moreover, the lead counterions dioleyl sulfosuccinate and bis(isotridecyl) sulfosuccinate bearing highly lipophilic alkyl tails provided a significant improvement in the hydrophobicity of the resulting complexes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Reverse micelle (RM) aggregates have a wide range of applications in various areas of science and technology. A continuous demand exists to replace interfacial surfactant molecules with various nonconventional amphiphiles. Ionic liquid (IL)-like surfactants (IL-surf's) constitute a class of such molecules that are being researched extensively. Here, we have formulated several water/IL-surf/oil microemulsions by optimizing the core droplet size with varying oil phases. The best composition of water/[BMIM][AOT]/IPM ([BMIM][AOT]: 1-butyl-3-methylimidazolium dioctyl sulfosuccinate; IPM: isopropyl myristate) was then analyzed in detail through experimental and computer simulations. Our results from DLS measurements suggest a structural transition from spherical aggregates in the parent water/[Na][AOT]/IPM solution to cylindrical droplets in the IL-surf-based system. The Raman and ATR-FTIR spectral analysis suggest a variation in the microstructure of the water/oil interface due to the differential interaction of the counterions with AOT headgroups and water. Molecular dynamics simulation results provided the direct image of the interface showing a structured versus uneven water/oil interface in [Na][AOT] versus [BMIM][AOT] RMs, where the larger [BMIM] cations weakly bind with the AOT headgroups due to their low charge density. Finally, an application of this IL-surf-based formulation was tested by carrying out a Heck cross-coupling reaction that showed significantly higher yield under milder reaction conditions.

Aerosol-OT reverse micelles represent a chemical construct where surfactant molecules self-assemble to stabilize water nanodroplets 1-10 nm in diameter. Although commonly assumed to adopt a spherical shape, all-atom molecular dynamics simulations and some experimental studies predict a nonspherical shape. If these aggregates are not spherical, then what shape do they take? Because the tools needed to evaluate the shape of something that lacks regular structure, order, or symmetry are not well developed, we present a set of three intuitive metrics─coordinate-pair eccentricity, convexity, and the curvature distribution─that estimate the shape of an amorphous object, and we demonstrate their use on a simulated aerosol-OT reverse micelle. These metrics are all well-established methods and principles in mathematics, and each provides unique information about the shape. Together, these metrics provide intuitive descriptions of amorphous shapes, facilitate ways to quantify those shapes, and follow their changes over time.