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Hyaluronic acid, a naturally occurring carbohydrate biopolymer in human tissues, finds wide application in cosmetics, medicine, and material science. Its anionic properties play a crucial role in its interaction with positively charged macromolecules and ions. Among these macromolecules, positively charged arginine molecules or polyarginine peptides demonstrate potential in drug delivery when complexed with hyaluronan. This study aimed to compare and elucidate the results of both experimental and computational investigations on the interactions between hyaluronic acid polymers and polyarginine peptides. Experimental findings revealed that by varying the length of polyarginine peptides and the molar ratio, it is possible to modulate the size, solubility, and stability of hyaluronan-arginine particles. To further explore these interactions, molecular dynamics simulations were conducted to model the complexes formed between hyaluronic acid polymers and arginine peptides. The simulations are considered in different molar ratios and lengths of polyarginine peptides. By analysis of the data, we successfully determined the shape and size of the resulting complexes. Additionally, we identified the primary driving forces behind complex formation and explained the observed variations in peptide interactions with hyaluronan.

High-resolution ultrasound spectroscopy (HR-US), size and ζ-potential titrations, and isothermal titration calorimetry (ITC) were used to characterize the interactions between hyaluronan and catanionic ion pair amphiphile vesicles composed of hexadecyltrimethylammonium-dodecylsulphate (HTMA-DS), dioctadecyldimethylammonium chloride (DODAC), and cholesterol. In addition to these methods, visual observations were performed with the selected molecular weight of hyaluronan. A very good correlation was obtained between data from size titration, HR-US, and visual observation, which indicated in lower charge ratios the formation of hyaluronan-coated vesicles. On the contrary, at higher charge ratios, coated vesicles disintegrated to a size of around 2000 nm. The intensity of these interactions and the disaggregation were dependent on the molecular weight of hyaluronan. All interactions studied by ITC showed strong exothermic behavior, and these interactions between vesicles and hyaluronan were confirmed from the first addition, independently of the molecular weight of hyaluronan.

This work is focused on the study of the effect of cholesterol on the properties of vesicular membranes of ionic amphiphilic pairs at different temperatures. The hexadecyltrimethylammonium-dodecyl sulfate ionic amphiphilic pair system with the addition of 10 mol % dioctadecyldimethylammonium chloride was chosen for a detailed study of vesicle properties. A large range of cholesterol concentrations (0-73 mol %) in the temperature range 10-80 °C was studied. Under these conditions, the size distribution, the membrane fluidity, and the surface layer were monitored together with the change in the mobility of water in the surface layer. Obtained quantities were correlated with each other and combined into appropriate graphs. It was found that in stable systems that meet the condition of unimodal size distribution with a PDI value lower than 0.3, temperature has virtually no effect on the size of vesicular systems. On the contrary, when studying the hydration and fluidity of the membrane, significant changes in these parameters were found, which, however, do not affect the short-term stability of these vesicular systems. The presented results thus indicate the possibility of adjusting the composition of the vesicular system in terms of fluidity and membrane hydration while maintaining short-term stability and size distribution.

Interactions in a cationic surfactant-hyaluronan system in water and in sodium chloride solution were investigated by high-resolution ultrasonic spectroscopy at 25 °C. Two alkyltrimethylammonium bromide surfactants of different chain lengths (tetradecyl and hexadecyl) were used; hyaluronan molecular weight ranged from 10 to 1750 kDa. Two main parameters-ultrasonic velocity and attenuation-were measured in the titration regime. Up to six different regions could be identified in the velocity titration profiles in water in a narrow interval of surfactant concentration. These regions differed primarily in the compressibility of structures formed in the system. The number of detected transitions was higher for the tetradecyl surfactant; therefore, the increased length of the hydrophobic chain simplified the details of the structure-forming behavior. The measurement of attenuation was much less sensitive and detected only the formation of microheterogeneous structures or visible phase separates. The richness of the titration profiles was depressed in salt solution, where essentially only two principal regions were observed. On the other hand, the effect of hyaluronan molecular weight on the positions of boundaries between regions was more significant in the presence of salt. Besides electrostatic interactions, hydrophobic interactions are also relevant for determining the behavior of hyaluronan-surfactant systems and the properties of formed complexes (aggregates).

Steady-state and time-resolved fluorescence and UV-vis techniques were used to study the formation and dissociation of acridine orange dimer in order to investigate hyaluronan-acridine orange, hyaluronan-CTAB (cetyltrimethylammonium bromide), polystyrenesulfonate-acridine orange, and polystyrenesulfonate-CTAB interactions in aqueous solution. Steady-state and time-resolved fluorescence and the dimer:monomer absorbance ratio of acridine orange (AO) were used to determine dimer formation on polymer chains of polyelectrolytes. Acridine orange clearly formed dimers on polystyrensulfonate chains as well as on hyaluronan, but we show that the electrostatic interaction is much weaker in the case of hyaluronan. After the addition of surfactant, we observed an enhancement of fluorescence intensity, indicating the dissociation of AO dimers into monomers and the replacement of acridine orange on polymer chains by surfactant molecules. Importantly, we show that surfactant molecules bind to polymer chains before the critical micelle concentration is reached and form the so-called "bottle-brush" structure.