Ibuprofen, a traditional drug that may impact the course of COVID-19 new effective formulation in nebulizable solution

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 1x106 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.publishedVersionFil: García Canclini, Néstor. Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: García Canclini, Néstor. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Porta, Daniela Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Porta, Daniela Josefina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Muñoz, Sonia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina. Instituto de Investigaciones en Ciencias de la Salud; Argentina; Argentina.Fil: Muñoz, Sonia Edith. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Alasino, Roxana Valeria. Ministerio de Ciencia y Tecnología de Córdoba. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina.Fil: Beltramo, Dante MiguelIcon. Ministerio de Ciencia y Tecnología de Córdoba. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina

Effect of ethylcellulose on the structure and stability of non-aqueous oil based propylene glycol emulsions

The hydrophobic polymer ethylcellulose (EC) has been used to structure vegetable oils and as a stabilizer of oil/water (o/w) emulsions, among other non food uses. in this work we show that EC dissolved in medium chain triglycerides (MCT) or soybean oil (SO) is able to stabilize non-aqueous emulsions of propylene glycol (PG) as a dispersed phase. Cream-like emulsions can be obtained at both low and high homogenization speeds which show a very good stability for at least one month without the requirement of co-surfactants. PG-in-oil emulsions at concentrations of EC below 5% (w/w) display pseudoplastic behavior and greater viscosity than the respective solutions of the polymer in MCT or SO. However, at concentrations of EC above 5% (w/w) firm gels are formed in MCI' or SO and after the addition of PG, the emulsions formed have lower viscosity than the original solutions of the polymer in MCI' or SO. Such effects were independent of the mean molecular weight (MMW) of the EC at high shear stress and inversely proportional at low shear stress. These results indicate that the stabilizing effect of EC in PG-in-oil emulsions might not be caused mainly by an increase in the viscosity of the continuous phase. Comparing all the results obtained, we can infer that EC, despite being insoluble in PG, is promoting interactions which are responsible for the observed effects.These PG-in-oil emulsions have interesting structural and flow properties which make them attractive to be used in food formulations, either as emulsions themselves or as potential vehicles for active ingredients. (C) 2014 Elsevier B.V. All rights reserved.CONICETCtr Excelenda Prod & Proc CEPROCOR, Buenos Aires, DF, ArgentinaConsejo Nacl Invest Cient & Tecn CONICET, Buenos Aires, DF, ArgentinaUniversidade Federal de São Paulo, Inst Ciencia & Tecnol, São Paulo, BrazilUniv Catalica Cordoba, Fac Ciencias Quim, Lab Biotecnol, Cordoba, ArgentinaUniv Nacl La Rioja, Dept Ciencias Exactas Fis & Natr, La Rioja, ArgentinaUniversidade Federal de São Paulo, Inst Ciencia & Tecnol, São Paulo, BrazilCONICET: PIP 11220100100502CONICET: PIP 11220090100732Web of Scienc

High Concentrations of Sodium Chloride Improve Microbicidal Activity of Ibuprofen against Common Cystic Fibrosis Pathogens

Ibuprofen (IBU-H), a widely used anti-inflammatory, also shows a marked antimicrobial effect against several bacterial species, including those involved in cystic fibrosis such as Pseudomona aeruginosa, methicillin resistant Staphylococcus aureus and Burkholderia cepacia complex. Additionally, our results show significant synergy between water soluble Na-ibuprofen (IBU-Na) and ionic strength. Salt concentrations above 0.5 M modify the zeta potential promoting the action of Na-IBU; thus, with 1 M sodium chloride, IBU-Na is ten times more efficient than in the absence of ionic strength, and the minimum effective contact time is reduced from hours to minutes. In short time periods, where neither IBU-Na nor controls with 1 M NaCl show activity, the combination of both leads to a reduction in the bacterial load. We also analyzed whether the changes caused by salt on the bacterial membrane also promoted the activity of other microbicide compounds used in cystic fibrosis like gentamicin, tobramycin and phosphomycin. The results show that the presence of ionic strength only enhanced the bactericidal activity of the amphipathic molecule of IBU-Na. In this respect, the effect of saline concentration was also reflected in the surface properties of IBU-Na, where, in addition to the clear differences observed between 145 mM and 1 M, singular behaviors were also found, different in each condition. The combination of anti-inflammatory activity and this improved bactericidal effect of Na-IBU in hypertonic solution provides a new alternative for the treatment of respiratory infections of fibrotic patients based on known and widely used compounds

Eudragit Films as Carriers of Lipoic Acid for Transcorneal Permeability

Diabetes mellitus (DM) is a highly prevalent disease affecting almost 10% of the world population; it is characterized by acute and chronic conditions. Diabetic patients have twenty-five times higher risk of going blind and developing cataracts early than the general population. Alpha-lipoic acid (LA) is a highly valuable natural antioxidant for the prevention and treatment of ophthalmic complications, such as diabetic keratopathy and retinopathy. However, its applicability is limited due to its low solubility in water; therefore, suitable systems are required for its formulation. In this work we developed an erodible insert based on Eudragit E100 (E PO) and Lipoic Acid (LA) for the delivery of this compound for the preventive treatment of ocular diseases especially in diabetic patients. Film evaluation was carried out by mechanical and thermal properties, mucoadhesivity, drug release, dynamic light scattering and corneal permeability as the concentration of LA increased. It was shown that upon LA release, it forms nanoparticles in combination with E PO that favor corneal permeation and LA retention in the cornea. These E PO-LA films also resulted non-irritable hence they are promising for their application in the treatment of ocular diseases