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

Abstract

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.

Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study

“…In addition, we recommended considering different models for water and its effect on protein-protein interaction in the absence and presence of these drugs. Another important aspect is to consider is the energetic and structural disturbance of the RBD-ACE2 complex under different concentration gradients of Ibuprofen on the surface or near the complex, this due to the apparent dependence of the antiviral activity shown by Ibuprofen with the bioavailability [45,94]. Why although there are no pharmacological and theoretical results in a similar direction, reflecting the novelty of our study, there is experimental research in a similar direction that has shown that Ibuprofen could contribute to the treatment of COVID-19 [45].…”

“…The WHO has indicated that there is no evidence to confirm an aggravation of COVID-19 infection with the administration of NSAIDs [30,31]. In fact, it has been reported that some NSAIDs could have some type of activity against viruses such as VZV [32], HCMV [32], HSV-1 [33], influenza virus A⁄ H1N1 subtype [34,35], VSV [36,37], EBOLA [38,39], HIV [40], JEV [41], CHIKV [42], SARS-CoV-1 [43], and recently against SARS-CoV-2 [35,44,45]. Additionally, many studies have been carried out that propose various targets for blocking virus recognition, importation and replication processes through the use of reused drugs, immunotherapies, interference strategies and various inhibitory compounds [46].…”

Improved protection of filtering facepiece through inactivation of pathogens by hypertonic salt solutions – A possible COVID-19 prevention device

“…Zhang et al, 2017 , Muñoz et al, 2018 , Michon et al, 0000 , García et al, 2020 , Qiu et al, 2017 , Han and Ivanovski , Scrivo et al, 2019 .…”

Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program

“…The mechanism by which NaIHS induces an apparent rapid improvement in oxygenation and other vital signs in COVID-19 patients is unknown, but multiple potential mechanisms can be evoked. These include the classical anti-inflammatory activity mediated by inhibition of prostaglandin and bradykinin synthesis, inhibition of thromboxane’s platelet aggregation, and reduction of reactive oxygen species by polymorphonuclear cells, as previously observed [ 27 ]. A potential benefit of nebulized hypertonic saline, recognized to be a mucolytic agent and used for this purpose in the treatment of cystic fibrosis and bronchiectasis, should not be overlooked.…”

“…Each vial comprised a single dose. A three-times daily dosing schema, each dose with 50 mg dose, was selected based on preliminary observations [ 21 , 27 ]. The total daily administered ibuprofen dose was therefore ≤ 150 mg, recognizing that some drug is exhaled.…”