Recycling COVID-19 health care wastes in bitumen modification: a case of disposable medical gloves.

Disposable medical gloves (DMGs) have long been used to mitigate the risk of direct exposure to diverse microorganisms and body fluids; hence, they are a critical weapon to protect patients and healthcare staff from infectious diseases. Measures to control the spread of COVID-19 have sparked the production of an excessive number of DMGs, most of which are eventually being disposed of in landfills. Untreated DMGs in landfills do not only pose a direct risk of transmitting coronavirus and other pathological germs but also pollute air, water, and soil dramatically. As a healthier alternative, recycling discarded polymer-rich DMGs into bitumen modification is considered to be a prospective waste management strategy applicable to the asphalt pavement industry. In this study, this conjecture is tested by examining two common DMGs - latex gloves and vinyl gloves - at four different percentages (1%, 2%, 3%, and 4% by weight). The morphological characteristics of DMG-modified specimens were inspected by using a high-definition scanning electron microscope (SEM) equipped with an energy dispersive X-ray analyzer (EDX). A wide range of laboratory tests including penetration, softening point temperature, ductility, and elastic recovery were undertaken to evaluate the impact of waste gloves on the conventional engineering properties of bitumen. Moreover, viscoelastic behavior and modification processing were studied by conducting the dynamic shear rheometer (DSR) test and the Fourier transform infrared spectroscopy (FTIR) analysis. Test results have revealed the outstanding potential of recycled DMG waste for modifying neat asphalt binder. More specifically, bitumens modified with 4% latex glove and 3% vinyl glove were seen as capable of superiorly withstanding permanent deformations caused by heavy axle loads at high service temperatures. Furthermore, it has been shown that 1.2 tons of modified binder would embed approximately 4000 pairs of recycled DMGs. This study shows that DMG waste can be used as a viable modifier, which would help open a new avenue for mitigating the environmental pollution arising from the COVID-19 pandemic.

Improved recovery of SARS-CoV-2 from wastewater through application of RNA and DNA stabilising agents.

Wastewater Based Epidemiology (WBE) has become an integral part of the public health effort to track the levels of SARS-CoV-2 within communities. Detection of SARS-CoV-2 in wastewater can be challenging due to relatively low levels of virus within the sample. The wastewater matrix is also comprised of commercial and domestically derived contaminants, as well as RNases, all of which can adversely affect RT-qPCR analysis. To improve SARS-CoV-2 detection within wastewater samples we investigated both the effect of template dilution (as a means to reduce RT-qPCR inhibition) and sample stabilisation via addition of DNA/RNA Shield™ and/or RNA Later™ (to prevent RNA degradation via RNases) as a means to improve viral fragment detection. Using both methodologies, a significant improvement in SARS-CoV-2 detection from wastewater samples was observed. No adverse effects of stabilising agent addition on downstream Next-Generation Sequencing workflows were detected.

Prevention of skin lesions caused by the use of protective face masks by an innovative gelatin-based hydrogel patch: Design and in vitro studies.

The recent Covid-19 pandemics led to the increased use of facial masks, which can cause skin lesions due to continuous pressure, tension and friction forces on the skin. A preventive approach is the inclusion of dressings between the face and the mask. However, there are still uncertainties about the protective effect of dressings and whether their use compromises the efficiency of masks. The current study aimed to develop and test the efficacy of a gelatin-based hydrogel patch to be placed between the mask and the facial area. Design of Experiment with a Quality by Design approach tools were used in the patch development and in vitro characterization was performed through rheological evaluation, ATR-FTIR and molecular docking studies. Furthermore, tribology studies were performed to test the patch performance. The results showed that the addition of excipients enhanced gelation temperature, elasticity and adhesiveness parameters. The interactions between excipients were confirmed by ATR-FTIR and molecular docking. The tribology assay revealed similar friction values at room and physiological temperature, and when testing different skin types. In conclusion, the physical properties and the performance evaluation reported in this study indicate that this innovative film-forming system can be used to prevent skin lesions caused by the continuous use of protective masks.

The role of lymphocyte transformation tests (LTT) in suspected severe delayed hypersensitivity reactions following COVID-19 vaccination.

Coronavirus (COVID-19) vaccines have proved to be effective in the pandemic response but can cause adverse events such as delayed hypersensitivity reactions (DHRs). Delayed-reading intradermal tests (IDT) to vaccines are limited by false-positive results and may reflect a cell-mediated rather than IgE-mediated immune response. Lymphocyte transformation test (LTT), which has been utilized in the diagnosis of drug allergy, may be helpful in suspected COVID-19 vaccine and/or its excipient-related DHRs. To investigate the use of LTT in two suspected cases of COVID-19 vaccine-induced DHRs, two patients with suspected DHRs to COVID-19 vaccination were tested by delayed-reading IDT and LTT against vaccines and their excipients. A 47-year-old man developed acute mixed-pattern hepatitis after the second dose of ChAdOx1 vaccine. LTT performed at 2 months post-vaccination revealed reactivity to the ChAdOx1 vaccine, polysorbate 80 and mildly to PEG 2050 but not BNT162b2 vaccine. Delayed-reading IDT returned negative to both vaccines and excipients. He tolerated BNT162b2 vaccination with no adverse events. A 36-year-old woman presented with subacute morbilliform eruption and hepatitis after the first dose of BNT162b2 vaccine. LTT performed 3 months later revealed reactivity to the BNT162b2 but not PEG 2050. Repeat LTT following subsequent natural Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) infection revealed reactivity to ChAdOx1 and NVX-CoV2373 vaccines but not polysorbate 80. Delayed-reading IDT remained negative. She proceeded with NVX-CoV2373 vaccination with no symptom recurrence. LTT may be a useful tool in suspected COVID-19 vaccine-related DHRs. Further evaluation with a larger patient cohort is required.

Betaine- and L-Carnitine-Based Ionic Liquids as Solubilising and Stabilising Agents for the Formulation of Antimicrobial Eye Drops Containing Diacerein.

The therapeutic efficacy of topically administered drugs, however powerful, is largely affected by their bioavailability and, thus, ultimately, on their aqueous solubility and stability. The aim of this study was to evaluate the use of ionic liquids (ILs) as functional excipients to solubilise, stabilise, and prolong the ocular residence time of diacerein (DIA) in eye drop formulations. DIA is a poorly soluble and unstable anthraquinone prodrug, rapidly hydrolysed to rhein (Rhe), for the treatment of osteoarthritis. DIA has recently been evaluated as an antimicrobial agent for bacterial keratitis. Two ILs based on natural zwitterionic compounds were investigated: L-carnitine C6 alkyl ester bromide (Carn6), and betaine C6 alkyl ester bromide (Bet6). The stabilising, solubilising, and mucoadhesive properties of ILs were investigated, as well as their cytotoxicity to the murine fibroblast BALB/3T3 clone A31 cell line. Two IL-DIA-based eye drop formulations were prepared, and their efficacy against both Staphylococcus aureus and Pseudomonas aeruginosa was determined. Finally, the eye drops were administered in vivo on New Zealand albino rabbits, testing their tolerability as well as their elimination and degradation kinetics. Both Bet6 and Carn6 have good potential as functional excipients, showing solubilising, stabilising, mucoadhesive, and antimicrobial properties; their in vitro cytotoxicity and in vivo ocular tolerability pave the way for their future use in ophthalmic applications.

Research Advances on the Stability of mRNA Vaccines.

Compared to other vaccines, the inherent properties of messenger RNA (mRNA) vaccines and their interaction with lipid nanoparticles make them considerably unstable throughout their life cycles, impacting their effectiveness and global accessibility. It is imperative to improve mRNA vaccine stability and investigate the factors influencing stability. Since mRNA structure, excipients, lipid nanoparticle (LNP) delivery systems, and manufacturing processes are the primary factors affecting mRNA vaccine stability, optimizing mRNA structure and screening excipients can effectively improve mRNA vaccine stability. Moreover, improving manufacturing processes could also prepare thermally stable mRNA vaccines with safety and efficacy. Here, we review the regulatory guidance associated with mRNA vaccine stability, summarize key factors affecting mRNA vaccine stability, and propose a possible research path to improve mRNA vaccine stability.

Allergic Contact Dermatitis and Patch Testing in Skin of Color Patients.

Objective: Skin of color patients face important health issues relevant to dermatologists, such as allergic contact dermatitis; however, there is a lack of information surrounding common allergens causing contact dermatitis that disproportionately affect skin of color patients, as well as interpreting patch testing in this population. Methods: Covidence, Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched to identify relevant articles studying allergic and irritant contact dermatitis in skin of color patients. Results: The most common positive reactions in African American patients included PPD, balsam of Peru, bacitracin, fragrance mix, and nickel. The most common positive reactions in Hispanic patients included Carba mix, nickel sulfate, and thiuram mix. The most common positive reactions in Asian patients included nickel sulfate, fragrance mix, and potassium dichromate. When interpreting patch test results in patients with higher Fitzpatrick skin types, positive patch tests presented with lichenification and hyperpigmentation, rather than erythema and vesicles. Furthermore, characteristic bright red or pink hues for positive results may appear violaceous or faint pink. Conclusions: Awareness of the common allergens associated with allergic contact dermatitis in patients of skin of color can help guide patch testing as an important diagnostic tool. Further research must be conducted regarding contact dermatitis in this patient population, especially given the relative lack of data surrounding Hispanic, Asian and Pacific Islander, and Native American patients.

A FluoroSpot B assay for the detection of IgA and IgG SARS-CoV-2 spike-specific memory B cells: Optimization and qualification for use in COVID-19 vaccine trials.

BACKGROUND: The generation of antigen-specific memory B cells is crucial to the long-term effectiveness of vaccines. When the protective antibodies circulating in the blood wane, memory B cells (MBC) can be rapidly reactivated and differentiated into antibody-secreting cells during a new infection. Such MBC responses are considered to be key in providing long-term protection after infection or vaccination. Here, we describe the optimization and qualification of a FluoroSpot assay to measure MBCs directed against the SARS-CoV-2 spike protein in the peripheral blood, for use in COVID-19 vaccine trials. METHODS: We developed a FluoroSpot assay enabling simultaneous enumeration of B cells secreting IgA or IgG spike-specific antibodies after polyclonal stimulation of peripheral blood mononuclear cells (PBMCs) with interleukin-2 and the toll-like receptor agonist R848 for 5 days. The antigen coating was optimized using a capture antibody directed against the spike subunit-2 glycoprotein of SARS-CoV-2 to immobilize recombinant trimeric spike protein onto the membrane. RESULTS: Compared to a direct spike protein coating, the addition of a capture antibody increased the number and the quality of detected spots for both spike-specific IgA and IgG secreting cells in PBMCs from COVID-19 convalescents. The qualification showed good sensitivity of the dual-color IgA-IgG FluoroSpot assay, with lower limits of quantitation of 18 background-subtracted (BS) antibody-secreting cells (ASCs)/well for spike-specific IgA and IgG responses. Linearity was demonstrated at values ranging from 18 to 73 and from 18 to 607 BS ASCs/well for spike-specific IgA and IgG, respectively, as was precision, with intermediate precision (percentage geometric coefficients of variation) of 12% and 26% for the proportion of spike-specific IgA and IgG MBCs (ratio specific/total IgA or Ig). The assay was specific, since no spike-specific MBCs were detected in PBMCs from pre-pandemic samples; the results were below the limit of detection of 17 BS ASCs/well. CONCLUSIONS: These results show that the dual-color IgA-IgG FluoroSpot provides a sensitive, specific, linear, and precise tool to detect spike-specific MBC responses. This MBC FluoroSpot assay is a method of choice for monitoring spike-specific IgA and IgG MBC responses induced by COVID-19 candidate vaccines in clinical trials.

Us vehicles sales. Evidence of persistence after COVID-19.

In this paper, the sales of vehicles in the US are examined to understand if the shock caused by the current COVID-19 pandemic has had permanent or transitory effects on its subsequent evolution. Using monthly data from January 1976 until April 2021 and fractional integration methods, our results indicate that the series reverts and the shocks tend to disappear in the long run, even when they appear to be long lived. The results also indicate that the COVID-19 pandemic has not increased the degree of persistence of the series but, unexpectedly, has slightly reduced its dependence. Thus, shocks are transitory, long lived but, as time goes by, the recovery seems to be faster, which is possibly a sign of the strength of the industry.

Evaluation of roadside air quality using deep learning models after the application of the diesel vehicle policy (Euro 6).

Euro 6 is the latest vehicle emission standards for pollutants such as CO, NO2 and PM, that all new vehicles must comply, and it was introduced in September 2015 in South Korea. This study examined the effect of Euro 6 by comparing the measured pollutant concentrations after 2016 (Euro 6-era) to the estimated concentrations without Euro 6. The concentration without Euro 6 was estimated by first modeling the air quality using various environmental factors related to diesel vehicles, meteorological conditions, temporal information such as date and precursors in 2002-2015 (pre-Euro 6-era), and then applying the model to predict the concentration after 2016. In this study, we used both recurrent neural network (RNN) and random forest (RF) algorithms to model the air quality and showed that RNN can achieve higher R2 (0.634 ~ 0.759 depending on pollutants) than RF, making it more suitable for air quality modeling. According to our results, the measured concentrations during 2016-2019 were lower than the concentrations predicted using RNN by - 1.2%, - 3.4%, and - 4.8% for CO, NO2 and PM10. Such reduction can be attributed to the result of Euro 6.

Extracellular Vesicles as Therapeutic Resources in the Clinical Environment.

The native role of extracellular vesicles (EVs) in mediating the transfer of biomolecules between cells has raised the possibility to use them as therapeutic vehicles. The development of therapies based on EVs is now expanding rapidly; here we will describe the current knowledge on different key points regarding the use of EVs in a clinical setting. These points are related to cell sources of EVs, isolation, storage, and delivery methods, as well as modifications to the releasing cells for improved production of EVs. Finally, we will depict the application of EVs therapies in clinical trials, considering the impact of the COVID-19 pandemic on the development of these therapies, pointing out that although it is a promising therapy for human diseases, we are still in the initial phase of its application to patients.

Encapsulation of Bromelain in Combined Sodium Alginate and Amino Acid Carriers: Experimental Design of Simplex-Centroid Mixtures for Digestibility Evaluation.

Bromelain has potential as an analgesic, an anti-inflammatory, and in cancer treatments. Despite its therapeutic effects, this protein undergoes denaturation when administered orally. Microencapsulation processes have shown potential in protein protection and as controlled release systems. Thus, this paper aimed to develop encapsulating systems using sodium alginate as a carrier material and positively charged amino acids as stabilizing agents for the controlled release of bromelain in in vitro tests. The systems were produced from the experimental design of centroid simplex mixtures. Characterizations were performed by FTIR showing that bromelain was encapsulated in all systems. XRD analyses showed that the systems are semi-crystalline solids and through SEM analysis the morphology of the formed systems followed a pattern of rough microparticles. The application of statistical analysis showed that the systems presented behavior that can be evaluated by quadratic and special cubic models, with a p-value < 0.05. The interaction between amino acids and bromelain/alginate was evaluated, and free bromelain showed a reduction of 74.0% in protein content and 23.6% in enzymatic activity at the end of gastric digestion. Furthermore, a reduction of 91.6% of protein content and 65.9% of enzymatic activity was observed at the end of intestinal digestion. The Lis system showed better interaction due to the increased stability of bromelain in terms of the amount of proteins (above 63% until the end of the intestinal phase) and the enzymatic activity of 89.3%. Thus, this study proposes the development of pH-controlled release systems aiming at increasing the stability and bioavailability of bromelain in intestinal systems.

Boosting the anti MERS-CoV activity and oral bioavailability of resveratrol via PEG-stabilized emulsomal nano-carrier: Factorial design, in-vitro and in-vivo assessments.

Resveratrol (RSV) is a phytoceutical polyphenolic compound exhibiting a well evidenced wide range of therapeutic activities. Unfortunately, its diminished aqueous solubility and extensive metabolism in gastro intestinal tract (GIT) and liver prohibit its biological activity and systemic availability. Herein the conducted study PEG stabilized emulsomes (PEMLs) were customized to enclose RSV aiming to boost its biological availability and antiviral activity. PEGylating the vesicles not only grant the promoted steric stability of the system but also being beneficial in exaggerating the intestinal permeability and extending the period of circulation of the drug, hence its targeted clinical use. The Investigation of the influence of predetermined variables on the physical characterization of formulae (entrapment efficiency EE%, particle size PS and zeta potential ZP) was implemented utilizing Design Expert® software. (F4) with desirability value (0.772), picked to be the optimal formula, which is fabricated utilizing 35 mg compritol as the lipidic core and 60 mg 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-Mpeg-2000). The dominance of the F4 relative to RSV dispersion was affirmed by the data acquired from ex-vivo and pharmacokinetic studies. In addition, F4 exhibited significant lower EC50 value (0.0127 µg/mL) relative to that of RSV dispersion(0.338 µg/mL) by around 26 times denoting the capability of the formulation to boost the antiviral activity. To a great extent, F4 was able to significantly suppress the inflammatory response and oxidative stress resulted from MERS-CoV infection on comparison with RSV dispersion. Finally, the potentiality of PEMLs as nano-panel with boosted both antiviral and oral bioavailability for RSV could be deduced based on the outcomes mentioned herein.

Probing Molecular Interactions of Antibody Drugs, Silicone Oil, and Surfactant at Buried Interfaces In Situ.

Antibody drugs have been rapidly developed to cure many diseases including COVID-19 infection. Silicone oil is commonly used as a lubricant coating material for devices used in the pharmaceutical industry to store and administer antibody drug formulations. However, the interaction between silicone oil and antibody molecules could lead to the adsorption, denaturation, and aggregation of antibody molecules, impacting the efficacy of antibody drugs. Here, we studied the molecular interactions between antibodies and silicone oil in situ in real time. The effect of the surfactant on such interactions was also investigated. Specifically, the adsorption dynamics of a bispecific antibody (BsAb) onto a silicone oil surface without and with different concentrations of the surfactant PS80 in antibody solutions were monitored. Also the possible lowest effective PS80 concentrations that can prevent the adsorption of BsAb as well as a monoclonal antibody (mAb) onto silicone oil were measured. It was found that different concentrations of PS80 are required for preventing the adsorption of different antibodies. Both BsAB and mAB denature on silicone oil without a surfactant. However, for a low surfactant concentration in the solution, although the surfactant could not completely prevent the antibody from adsorption, it could maintain the native structures of adsorbed BsAb and mAb antibodies on silicone oil. This is important knowledge, showing that to prevent antibody aggregation on silicone oil it is not necessary to add surfactant to a concentration high enough to completely minimize protein adsorption.

Recent developments in lactose blend formulations for carrier-based dry powder inhalation.

Lactose is the most commonly used excipient in carrier-based dry powder inhalation (DPI) formulations. Numerous inhalation therapies have been developed using lactose as a carrier material. Several theories have described the role of carriers in DPI formulations. Although these theories are valuable, each DPI formulation is unique and are not described by any single theory. For each new formulation, a specific development trajectory is required, and the versatility of lactose can be exploited to optimize each formulation. In this review, recent developments in lactose-based DPI formulations are discussed. The effects of varying the material properties of lactose carrier particles, such as particle size, shape, and morphology are reviewed. Owing to the complex interactions between the particles in a formulation, processing adhesive mixtures of lactose with the active ingredient is crucial. Therefore, blending and filling processes for DPI formulations are also reviewed. While the role of ternary agents, such as magnesium stearate, has increased, lactose remains the excipient of choice in carrier-based DPI formulations. Therefore, new developments in lactose-based DPI formulations are crucial in the optimization of inhalable medicine performance.

Assessment of Immediate Allergic Reactions After Immunization With the Pfizer BNT162b2 Vaccine Using Intradermal Skin Testing With the COVID-19 Vaccines.

BACKGROUND: Allergic reactions to the coronavirus disease 2019 (COVID-19) vaccines have raised concerns, particularly as repeated doses are required. Skin tests with the vaccines excipient were found to be of low value, whereas the utility of skin tests with the whole vaccine is yet to be determined. OBJECTIVE: To evaluate a panel of skin tests and the outcomes of subsequent doses of immunization among subjects who suffered an immediate allergic reaction to the BioNTech (BNT162b2) COVID-19 vaccine. METHODS: Between March and December 2021, patients who experienced symptoms consistent with immediate allergic reactions to the BNT162b2 vaccine and were referred to the Sheba Medical Center underwent skin testing with polyethylene glyol (PEG)-containing medicines, Pfizer-BNT162b2, and Oxford-AstraZeneca vaccine (AZD1222). Further immunization was performed accordingly and under medical observation. RESULTS: A total of 51 patients underwent skin testing for suspected allergy to the COVID vaccines, of which 38 of 51 (74.5%) were nonreactive, 7 of 51(13.7%) had no skin sensitization but suffered a clinical reaction during skin testing (mainly cough), and 6 of 51 (11.7%) exhibited immediate skin sensitization. Both skin sensitization and cough during testing were related to a higher use of adrenaline following immunization (P = .08 and P = .024, respectively). Further immunization with the BNT162b2 vaccine was recommended unless sensitization or severe reaction to previous immunization was evident. The latter were referred to be tested/receive the alternative AZD1222 vaccine. Ten patients underwent skin testing with AZD1222: 2 of 10 (20%) demonstrated skin sensitization to both vaccines; thus, 8 of 10 were immunized with the AZD1222, of which 2 of 8 (25%) had allergic reactions. CONCLUSIONS: Immediate allergic reactions to COVID-19 vaccines are rare but can be severe and reoccur. Intradermal testing with the whole vaccine may discriminate sensitized subjects, detect cross-sensitization between vaccines, and enable estimation of patients at higher risk.

COVID vaccination can be performed in patients with a history of allergic reactions to the vaccines or their components: experience from a specialist clinic in South Australia.

BACKGROUND: The development of vaccines against SARS-CoV2 has been a key public health response to the COVID-19 pandemic. However, since their introduction, there have been reports of anaphylactic reactions to vaccines in individuals with history of allergic reactions to other vaccines, excipients or to COVID vaccines. AIM: A dedicated adult COVID vaccine allergy clinic with a standardised allergy testing protocol was set up to investigate safety and suitability of available COVID vaccines in Australia. METHODS: Patients referred to a state-wide COVID-19 vaccine allergy clinic between March and August 2021 with a history of allergy underwent skin-prick testing and intradermal testing to both available vaccine formulations (BNT162b2 and ChAdOx1-S), excipients (polyethylene glycol and polysorbate 80), excipient-containing medications and controls. Basophil activation testing was conducted in few subjects with convincing history of immediate type reactions. RESULTS: Fifty-three patients underwent testing for possible excipient allergy (n = 19), previous non-COVID vaccine reaction (n = 13) or previous reaction to dose 1 of COVID-19 vaccine (n = 21). Patients were predominantly female (n = 43, 81%), aged 18-83 (median 54) years. Forty-four patients tested negative and 42 of these received at least their first dose of a COVID-19 vaccine. Nine patients tested positive to excipients or excipient-containing medication only (n = 3), or vaccines (n = 6). Five patients were positive to just BNT162b2, 3/5 have been vaccinated with ChAdOx1-S. One who was skin test positive to both vaccines, but negative BAT to ChAdOx1-S was successfully vaccinated with ChAdOx1-S. CONCLUSION: Even in a high-risk population, most patients can be vaccinated with available COVID-19 vaccines. This paper reports local experiences using a combined allergy testing protocol with skin testing and BAT during the pandemic.

Remdesivir powders manufactured by jet milling for potential pulmonary treatment of COVID-19.

Remdesivir is one of the effective drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, the study on inhalable regimen is currently limited though COVID-19 is respiratory diseases and infects lung area. This work aims to prepare inhalable remdesivir formulations and verify their effectiveness through in vitro evaluations. Formulations containing different ratios of jet-milled inhalable remdesivir (5, 10, 20,40, and 70%) with excipients were produced and characterized in terms of the particle size distribution, particle morphology, flowability, water content, crystallinity, the water sorption and desorption capabilities, and the aerodynamic performance. Results indicating that drug loading are a vital factor in facilitating the dispersion of remdesivir dry powder, and the ternary excipient plays a negligible role in improving aerosol performance. Besides, the 70% remdesivir with lactose carrier (70% RD-Lac) was physically stable and retain high aerosol performance after conditioned at 40 °C and 75% RH for a month. Therefore, formulation 70% RD-Lac might be recommended as a candidate product for the potential treatment of COVID-19.

Nanoformulated Remdesivir with Extremely Low Content of Poly(2-oxazoline)-Based Stabilizer for Aerosol Treatment of COVID-19.

The rise of the novel virus SARS-CoV2 which causes the disease known as COVID-19 has led to a global pandemic claiming millions of lives. With no clinically approved treatment for COVID-19, physicians initially struggled to treat the disease, and a need remains for improved antiviral therapies in this area. It is conceived early in the pandemic that an inhalable formulation of the drug remdesivir which directly targets the virus at the site of infection could improve therapeutic outcomes in COVID-19. A set of requirements are developed that would be conducive to rapid drug approval: 1) try to use GRAS reagents 2) minimize excipient concentration and 3) achieve a working concentration of 5 mg/mL remdesivir to obtain a deliverable dose which is 5-10% of the IV dose. In this work, it is discovered that Poly(2-oxazoline) block copolymers can stabilize drug nanocrystal suspensions and provide suitable formulation characteristics for aerosol delivery while maintaining antiviral efficacy. The authors believe POx block copolymers can be used as a semi-ubiquitous stabilizer for the rapid development of nanocrystal formulations for new and existing diseases.