No abstract

The cationic acrylate polymer Eudragit E100 (E100) produces a biphasic effect on the stability of casein micelles disrupting their internal structure. These results suggested that this polymer could have some amphipathic character. Therefore, in this study the polymer was characterized with respect to its interaction with different amphipathic systems (bile-acid micelles, lipoproteins and liposomes), cell membranes (red blood cells) and virus membranes (Herpes simplex type 2 virus). As with caseins, a biphasic effect was observed with bile acids with a precipitation phase at low polymer/bile acid ratio and a solubilization phase when the polymer concentration was increased. Upon interaction with human plasma, an important reduction in cholesterol and triglycerides was observed upon remotion of E100 by a rise in pH to 8.5 and centrifugation. In agreement with this finding, an important reduction in plasma lipoproteins was observed upon its treatment with E100 and further remotion by pH rise and centrifugation. However, the amount of the major protein components of human plasma and the activity of several enzymes and antibodies were not affected by their treatment with E100. The membrane-destabilizing properties of E100 were confirmed by its lytic activity on liposomes and red blood cells and by an important antiviral effect of E100 on Herpes simplex virus type 2. Altogether, these results show that, despite its water solubility and cationic character, E100 displays a significative amphipathic and membrane-destabilizing character with potential biotechnological applications. [diagram in text].

When whole or skim milk was incubated with the cationic acrylate polymer Eudragit E100, a biphasic effect on the stability of casein micelles was observed. A precipitation phase was observed at low polymer/casein ratios. Strikingly, a solubilization phase of the aggregates was observed when the ratios of polymer/casein were increased. Purified alpha(s)-, beta-, and kappa-caseins or dephosphorylated caseins were equally precipitated and resolubilized by the cationic polymer, indicating no special selectivity for a particular protein or phosphate residue for these events. An increase in the size of the aggregates as the optimum precipitating amount of Eudragit E100 was reached suggests a crossbridging of the micelles by the polymer. The inhibition of the precipitation phase by high ionic strength indicates that electrostatic interactions play a critical role in complex formation. Furthermore, a dramatic reduction in size of the protein colloidal particles upon solubilization of the aggregates was observed by dynamic light scattering, indicating a dissociation of the micellar structure. Taken together, the results indicate that at low concentration Eudragit E100 may act as a precipitant of casein micelles, mainly by ionic interaction and at high concentration as an amphipathic agent, solubilizing casein micelles with a disruption of their internal structure.

The traditional formulation of ibuprofen is poorly soluble in water, so the administered dose must be 10 times higher than the dose required for a therapeutic effect. The development of a hydrosoluble form of ibuprofen can be a strategy to reach a high concentration in the lungs by using modern inhalation devices. Therefore, the development of an inhalable formulation with high bioavailability in the lungs was the leitmotiv of our investigation. The hypertonic ibuprofen solution to be nebulized (NIH) presents great relevant characteristics: bactericidal, virucidal, mucolytic and has a known anti-inflammatory property. Bactericidal and virucidal effects are related to the physico-chemical properties of Na-ibuprofenate as an amphipathic molecule. It has the capability to insert into the bilayer membranes destabilizing the structure, altering its biological properties and avoiding the duplication or infection. Our preliminary results indicate that the presence of this high ionic strength solution reduces 10 times the amount of ibuprofen necessary to kill bacteria, but also the time to kill 1x10 6 bacteria, from 4 h (in its absence) to only three minutes (in its presence). That was observed using Pseudomona aeruginosa, methicillin-resistant Staphylococcus aureus and Burkholderia cepacia. Also, "in vitro'' ibuprofen demonstrated virucidal activity against the so-called enveloped virus, a family that includes coronavirus strain (2019-nCoV). We observed too, the markedly reduced local inflammation in the airways after administering NIH lays on its ability to inhibit the enzyme cyclooxygenase and to markedly diminish reactive oxygen species (ROS). Other investigators also showed the importance of actin in the rapid spread of virus infection. Furthermore, reorganization of the actin filaments is a key step in lung inflammation induced by systemic inflammatory responses caused by SARS-CoV-2. These findings suggest that the interaction between actin proteins and S1 is involved in the 2019-nCoV infection and pathogenesis. Consequently, the possibility of interfering in this interaction could represent a valid hypothesis for the development of promising therapeutic and prevention strategies. In conclusion, we consider that treating people with COVID-19 with NIH may be beneficial and an opportunity to contribute for the current global health emergency.