The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19.

Dry skin is a major dermatological problem and consumer research indicates that although current moisturizers are effective they are not completely meeting consumer expectation. Several technological approaches have been taken but influencing stratum corneum (SC) lipid phase behaviour as a novel water permeability barrier-enhancing and moisturizing mechanism has only been started to be investigated recently. Both the long periodicity SC lipid lamellar phase and the orthorhombic lipid packing state have been proposed to define optimal SC water permeability barrier properties. Several lipophillic moisturizers have been tested for their ability to modify SC lipid lateral packing namely glyceryl monoisostearate (GMIS), isopropyl isostearate (IPIS) and isostearyl isostearate (ISIS) of which IPIS and ISIS are reported to induce the orthorhombic phase. Despite the improvements in the lateral packing of SC lipids, these ingredients have been shown not to improve transepidermal water loss. However, using a novel skin surface water loss method we have observed for the first time significant improvements in SC water permeability barrier function for ISIS compared with IPIS, GMIS and petrolatum. However, using synthetic membranes and measuring water vapour transport rates we showed that the isostearyl esters were not occlusive like petrolatum. As the effects of ISIS were not because of what would be considered as true occlusion, we propose that the differences in the SC water permeability barrier properties from use of ISIS to the other ingredients tested are because of its reported effects on SC lipid phase behaviour. Further studies probably using spectroscopic approaches, however, will be needed to specifically test this hypothesis in vivo.

SARS-CoV-2 uses the human cell surface protein angiotensin converting enzyme 2 (ACE2) as the receptor by which it gains access into lung and other tissue. Early in the pandemic, there was speculation that a number of commonly used medications—including ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs)—have the potential to upregulate ACE2, thereby possibly facilitating viral entry and increasing the severity of COVID-19. We investigated the influence of the NSAIDS with a range of cyclooxygenase (COX)1 and COX2 selectivity (ibuprofen, flurbiprofen, etoricoxib) and paracetamol on the level of ACE2 mRNA/protein expression and activity as well as their influence on SARS-CoV-2 infection levels in a Caco-2 cell model. We also analysed the ACE2 mRNA/protein levels and activity in lung, heart and aorta in ibuprofen treated mice. The drugs had no effect on ACE2 mRNA/protein expression and activity in the Caco-2 cell model. There was no up-regulation of ACE2 mRNA/protein expression and activity in lung, heart and aorta tissue in ibuprofen-treated mice in comparison to untreated mice. Viral load was significantly reduced by both flurbiprofen and ibuprofen at high concentrations. Ibuprofen, flurbiprofen, etoricoxib and paracetamol demonstrated no effects on ACE2 expression or activity in vitro or in vivo. Higher concentrations of ibuprofen and flurbiprofen reduced SARS-CoV-2 replication in vitro.

Humectant and occlusive technologies have traditionally been used for the treatment of dry skin. Originally, non-lamellar-forming ingredients were used such as petrolatum but recent research has shown the advantage of using lamellar-forming ingredients such as ceramides, pseudoceramides and phospholipids in the relief of dry skin. Nevertheless, the importance of using lipid-phase transition inducers, such as long-chain fatty acids, has not been studied clinically. The evaluation of a novel complex of lipophilic ingredients was of interest: cetyl alcohol, isostearyl isostearate, potassium cetyl phosphate, cetyl behenate and behenic acid. The combination of all these ingredients was shown to be more effective than any single component in water vapour transmission rate studies. This was thought to be owing to the formation of a unique structural organization of the lipids upon dry-down from an O/W emulsion as was examined by X-ray diffraction and optical microscopy. When evaluated clinically in a randomized double-blind and vehicle-controlled moisturization efficacy trial, this novel blend of ingredients was shown to not only improve the visible signs of skin dryness to a significantly greater extent than a comparable mineral oil-containing vehicle but also then maintain a better skin condition during the regression no-treatment phase of the study. This combination of ingredients offers a new technology option for the treatment of dry skin.

Objective: The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) relates not only to the individual NSAID used but also to differences in formulation design. The aim of this study was to investigate the fundamental differences in ibuprofen and diclofenac drug delivery vehicles, specifically gels and plasters, compared to a recently launched 200 mg ibuprofen medicated plaster and characterize the resulting dermatologic-pharmacokinetic profiles into and through ex vivo human skin layers. Methods: In vitro skin permeation testing over 24 h and sacrificial timepoint penetration experiments (at 1, 4, 8, 12, and 24 h) were conducted using an automated flow-through diffusion cell system. The amount of drug delivered to the epidermis, dermis, and receptor solution (representing deeper tissue) was determined by liquid chromatography-tandem mass spectrometry. Skin protein binding of ibuprofen and diclofenac was investigated by spiking skin homogenate with increasing concentrations of each drug and determining the fraction unbound. Results: Differences were observed in the amount of drug recovered at sacrificial timepoints and rate at which drug was delivered to the target site between plaster and gel formulations of ibuprofen and diclofenac and between plaster formulations of the same drug (ibuprofen). While the amount of drug quantified at sacrificial timepoints did not necessarily determine in vivo flux rates, differences in drug distribution within the skin layers indicated where drug reservoirs were formed. Conclusions: These findings highlight the importance of intelligent formulation design in determining NSAID delivery through skin layers. Further work is required to quantify drug delivery into deeper tissues and the resultant local anti-inflammatory effects.