Purpose: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease that severely impairs patient's life quality and represents significant therapeutic challenge due to its pathophysiology arising from skin barrier dysfunction. Topical corticosteroids, the mainstay treatment for mild to moderate AD, are usually formulated into conventional dosage forms that are impeded by low drug permeation, resulting in high doses with consequent adverse effects, and also lack properties that would strengthen the skin barrier. Herein, we aimed to develop biomimetic lamellar lyotropic liquid crystals (LLCs), offering a novel alternative to Methods: In screening studies, pseudoternary phase diagrams alongside polarized light microscopy (PLM) and viscosity measurements were utilized. Next, the selected LCCs underwent comprehensive characterization via PLM, small-angle X-ray scattering, differential scanning calorimetry, and rheological analysis. Lastly, their performance was evaluated and compared with the commercially available reference medicine in chemical stability study, in vitro permeation testing, in vitro safety assessment using cell proliferation assay, inverted light microscopy, and Raman mapping of keratinocytes, besides gap closure assay performed by live-cell imaging. Results: Formulation (L/T)Ho30, containing the highest amount of lecithin/Tween 80 mixture (21%) and hempseed oil (28%), demonstrated lamellar microstructure with high skin hydration potential and favourable rheological features for skin administration. Moreover, in comparison with the reference medicine, it stood out by providing suitable chemical BD (betamethasone dipropionate) stability, improved 3-fold BD permeation, and excellent biocompatibility with over 85% cell proliferation at all tested concentrations, ensuring keratinocytes' integrity, as well as promoting skin healing with gap closure observed after 36 hours. Conclusion: Unique multi-target drug delivery strategy depicted in newly developed bioinspired lamellar LCCs structurally resembling stratum corneum intercellular lipids, with incorporated BD drug, and composed of multifunctional components that synergistically strengthen skin barrier, was presented here and shows a promising approach for improved AD treatment.

Nano- and micro-sized vesicular and colloidal structures mediate cell–cell communication. They are important players in the physiology of plants, animals, and humans, and are a subject of increasing interest. We investigated the effect of three surfactants, N-cetylpyridinium chloride (CPC), sodium dodecyl sulfate (SDS), and Triton X-100 (TX100), and two anionic polyelectrolytes, sodium polystyrene sulfonate (NaPSS) and sodium polymethacrylate (NaPMA), on nanoliposomes. In addition, the effect of SDS and TX100 on selected biological membranes (erythrocytes and microalgae) was investigated. The liposomes were produced by extrusion and evaluated by microcalorimetry and light scattering, based on the total intensity of the scattered light (I_tot), hydrodynamic radius (R_h), radius of gyration (R_g), shape parameter p (=R_h/R_g,0), and polydispersity index. The EPs shed from erythrocytes and microalgae Dunaliella tertiolecta and Phaeodactylum tricornutum were visualized by scanning electron microscopy (SEM) and analyzed by flow cytometry (FCM). The R_h and I_tot values in POPC liposome suspensions with added CPC, SDS, and TX100 were roughly constant up to the respective critical micelle concentrations (CMCs) of the surfactants. At higher compound concentrations, I_tot dropped towards zero, whereas R_h increased to values higher than in pure POPC suspensions (R_h ≈ 60–70 nm), indicating the disintegration of liposomes and formation of larger particles, i.e., various POPC–S aggregates. Nanoliposomes were stable upon the addition of NaPSS and NaPMA, as indicated by the constant R_h and I_tot values. The interaction of CPC, SDS, or TX100 with liposomes was exothermic, while there were no measurable heat effects with NaPSS or NaPMA. The SDS and TX100 increased the number density of EPs several-fold in erythrocyte suspensions and up to 30-fold in the conditioned media of Dunaliella tertiolecta at the expense of the number density of cells, which decreased to less than 5% in erythrocytes and several-fold in Dunaliella tertiolecta. The SDS and TX100 did not affect the number density of the microalgae Phaeodactylum tricornutum, while the number density of EPs was lower in the conditioned media than in the control, but increased several-fold in a concentration-dependent manner. Our results indicate that amphiphilic molecules need to be organized in nanosized particles to match the local curvature of the membrane for facilitated uptake. To pursue this hypothesis, other surfactants and biological membranes should be studied in the future for more general conclusions.

Modern isothermal titration calorimetry instruments give great precision, but for comparable accuracy they require chemical calibration. For the heat factor, one recommended process is HCl into the weak base TRIS. In studying this reaction with a VP-ITC and two Nano-ITCs, we have encountered some problems, most importantly a titrant volume shortfall Δv ≈ 0.3 μL, which we attribute to diffusive loss of HCl in the syringe tip. This interpretation is supported by a mathematical treatment of the diffusion problem. The effect was discovered through a variable-v protocol, which thus should be used to properly allow for it in any reaction that similarly approaches completion. We also find that the effects from carbonate contamination and from OH^- from weak base hydrolysis can be more significant that previously thought. To facilitate proper weighting in the least-squares fitting of data, we have estimated data variance functions from replicate data. All three instruments have low-signal precision of σ ≈ 1 μJ; titrant volume uncertainty is a factor of ∼2 larger for the Nano-ITCs than for the VP-ITC. The final heat factors remain uncertain by more than the ∼1 % precision of the instruments and are unduly sensitive to the HCl concentration.

To understand the impact of alkaline counterions on the self-assembly of atypical dianionic surfactants, we synthesized a series of novel amphiphilic compounds featuring a bulky dianionic head based on closo-dodecaborate and a hydrophobic alkoxy tail connected via short linkers of different complexation ability toward alkaline cations. The synthetic strategy relied on the opening of cyclic oxonium derivatives by activated alcohol, enabling the attachment of hydrophobic chains to the boron cluster framework. The synthesis of novel surfactants with high cationic purity free from contaminating ions or additional inorganic salts is described. Self-assembly of the dodecaborate-based surfactants at the air-water interface and in aqueous solutions was investigated using tensiometry, various NMR spectroscopy techniques, dynamic light scattering, and all-atom MD simulations. Interestingly, despite their dianionic heads, the surfactants form compact monolayers in cases in which efficient binding of counterions to surfactant dianions occurs. MD simulations suggested relatively small surfactant micelles above the critical micelle concentration, which was confirmed by light scattering analysis. There is evidence that their aggregation number and morphology are strongly dependent on counterion immobilization. The mobility of counterions was observed directly by ⁷Li, ²³Na, ³⁹K, and ¹³³Cs NMR spectroscopy, which allowed us to understand the binding abilities of linkers and dianionic heads toward counterions.

Using experiments based on the NaCl dilution calibration method, we examine several previously unstudied instrumental effects that can lead to systematic errors in isothermal titration calorimetry (ITC). We confirm earlier results that power feedback can affect estimated heats and find further that it can also affect cell temperature and introduce temperature "noise." To estimate effects from loss of titrant from the syringe through diffusion, and concentration changes in the cell from mixing with the overflow volume, we conduct experiments with injections separated by time intervals Δt from 8 to 60 min, giving run durations from 6 h to over 2 days. Because the effects are small, we have developed a global least-squares fitting algorithm to analyze 20 datasets simultaneously, from which three parameters governing diffusion and mixing ("leakage") are estimated, along with calibration parameters for heat and cell volume. Expressed as an effective volume loss from the syringe, Δv_dif is found to be of order ∼0.03 μL per injection for NaCl into water. Its effect is predicted to be negligible in many ITC applications. The effects from leakage are more significant but their neglect is still predicted to affect both NaCl calibration and 1:1 binding results by ∼1 %, which is marginally significant for calibration but seldom so for 1:1 binding. The calibration results for the cell volume V₀ are particularly sensitive to temperature and to the literature source for the relative molar enthalpy function for NaCl(aq).