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Hypothesis: Amino acid-based surfactants have been proposed as skin permeation enhancers. In this work, we investigated the potentiality of two arginine-based amphiphiles as permeation enhancers by studying their interaction with stratum corneum (SC) model lipid membranes., Experiments: N α -benzoyl arginine decyl- and dodecylamide were tested in comparison with the classical enhancer, oleic acid, and the non-enhancer, stearic acid. Two complementary approaches were used: lipid monolayers, taken as models of the unit film layer of SC, and atomistic molecular dynamics simulations., Findings: The arginine-based amphiphiles studied were able to be incorporated into the SCM membrane and alter its rheological and structural properties by disordering the lipid chains, enhancing membrane elasticity, and thinning the overall membrane. They also affected the lateral structure of heterogeneous SC membranes at the nanoscale by relaxing and rounding the domain borders. Our work shows that the alteration observed of the overall rheological and structural properties of the SC membranes appears to be a shared ability for several amphiphilic permeation enhancers. Our results encourage future exploration of those amphiphiles as skin permeation enhancers., 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 Elsevier Inc. All rights reserved.)

Objectives: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN)., Methods: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease., Results: Forty-two patients with PAN received a total of 53 biologic courses, including TNF-α blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases and other biologics in 10 cases. TNF-α blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission, partial response, treatment failure and treatment discontinuation due to severe adverse events occurred in, respectively, 40%, 13%, 40% and 7% of patients receiving TNF-α blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the three biologics, leading to early biologics discontinuation in only three cases., Conclusion: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cationic amino acid-based surfactants are known to interact with the lipid bilayer of microorganism resulting in cell death through a disruption of the membrane topology. To elucidate the interaction of a cationic surfactant synthesized in our lab, investigations involving N α -benzoyl-arginine decyl amide (Bz-Arg-NHC 10 ), and model membranes composed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were done. Bz-Arg-NHC 10 was able to penetrate into DPPC monolayers up to a critical pressure of 59.6 mN m -1 . Differential scanning calorimetry revealed that as the concentration of Bz-Arg-NHC 10 increased, the main transition temperature of DPPC slightly decreased. Atomic force microscopy (AFM) in situ experiments performed on supported DPPC bilayers on mica allowed monitoring the changes induced by Bz-Arg-NHC 10 . DPPC bilayer patches were partially removed, mainly in borders and bilayer defects for 50 µM Bz-Arg-NHC 10 solution. Increasing the concentration to 100 µM resulted in a complete depletion of the supported bilayers. Surface plasmon resonance (SPR) experiments, carried out with fully DPPC bilayers covered chips, showed a net increase of the SPR signal, which can be explained by Bz-Arg-NHC 10 adsorption. When patchy DPPC bilayers were formed on the substrate, a SPR signal net decrease was obtained, which is consistent with the phospholipids' removal observed in the AFM images. The results obtained suggest that the presence of the benzoyl group attached to the polar head of our compound would be the responsible of the increased antimicrobial activity against gram-negative bacteria when compared with other arginine-based surfactants.

The strong UV absorption of the bromide in aqueous solution undergoes a remarkable red shift of more than 10 nm induced by the addition of the salts that constitute a saline buffer. The maximum absorption wavelength of the bromide is displaced from approximately 194 nm in ultrapure water to wavelengths above 200 nm, depending on the composition of the solution. The bromide spectrum as counterion of the cetyltrimethylammonium in the surfactant CTAB also shows sensitivity to the aggregation behavior of the tensioactive, being able to detect intermolecular interactions even at concentrations lower than the critical micelle concentration. And, when the micelles are assembled, the bromide absorption detects the interfacial rearrangements caused by the incorporation of ions. To know more about those interfacial features, the pyrene molecular probe was used, taking advantage of the extensive knowledge of its spectroscopy. Pyrene verifies the existence of changes in the interfacial organization which confirm that the sensitivity of the bromide spectrum is based on the ability of the ion to detect its microenvironment, and therefore reaffirms that its absorption spectrum can be used as a local sensor. The present work encourages the use of bromide as a sensor ion in the UV region between 190 and 210 nm, which would avoid the introduction of external molecular probes that could disturb the system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A novel arginine-based cationic surfactant N α -benzoyl-arginine dodecylamide (Bz-Arg-NHC 12 ) was synthesized in our laboratory. In this paper we study the interaction of Bz-Arg-NHC 12 with sheep and human red blood cells (SRBC and HRBC respectively) due to their different membrane physicochemical/biophysical properties. SRBC demonstrated to be slightly more resistant than HRBC to the hemolytic effect of the surfactant, being the micellar structure responsible for the hemolytic effect in both cases. Moreover, besides the hemolytic effect, a dual behavior was observed for the surfactant studied: Bz-Arg-NHC 12 was also able to protect red blood cells against hypotonic lysis for HRBC in a wide range of surfactant concentrations. However, the degree of protection showed for SRBC was about 50% lower than for HBRC. In this regard, a remarkable volume expansion was evidenced only for SRBC treated with Bz-Arg-NHC 12 , although no correlation with the antihemolytic potency (pAH) was found. On the contrary, our surfactant showed a greater pAH when human erythrocytes were submitted to hypotonic stress, with a low volume expansion, showing a higher amount of solubilized phospholipids in the supernatant when compared with SRBC behavior. Surface plasmon resonance measurements show the molecular interaction of the surfactant with lipid bilayers from HRBC and SRBC lipids, demonstrating that in the latter neither microvesicle release or lipid extraction occurred. Our results demonstrate that the volume expansion of erythrocytes is not the only mechanism responsible for the protection by surfactants against hypotonic hemolysis: volume expansion could be compensated via microvesicle release or by the extraction of membrane components upon collisions between red blood cells and surfactant aggregates depending on the membrane composition., (Copyright © 2018 Elsevier B.V. All rights reserved.)