Nebulization of single-chain tissue-type and single-chain urokinase plasminogen activator for treatment of inhalational smoke-induced acute lung injury

Surasarang, Soraya Hengsawas; Sahakijpijarn, Sawittree; Florova, Galina; Komissarov, Andrey A.; Nelson, Christina; Enkhbaatar, Perenlei; Fukuda, Seisuke; Wolfson, Marla R.; Shaffer, Thomas H.; Idell, Steven; Williams, Robert O.

doi:10.1016/j.jddst.2018.04.013

Cited by 3 publications

(1 citation statement)

References 79 publications

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“…The dispersions were put on ice to separate the dispersion into two phases, including PFC phase (bottom layer) and aqueous phase (upper layer). The upper layer was collected and analyzed for the protein content by BCA assay and the enzyme activity by kinetic activity assay and then the specific enzyme activity was calculated as described previously 30 …”

Section: Methodsmentioning

confidence: 99%

Perfluorochemical‐facilitated plasminogen activator delivery to the airways: A novel treatment for inhalational smoke‐induced acute lung injury

Wolfson

Enkhbaatar

Fukuda

et al. 2020

Clinical & Translational Med

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Background Effective clinical management of airway clot and fibrinous cast formation of severe inhalational smoke‐induced acute lung injury (ISALI) is lacking. Aerosolized delivery of tissue plasminogen activator (tPA) is confounded by airway bleeding; single‐chain urokinase plasminogen activator (scuPA) moderated this adverse effect and supported transient improvement in gas exchange and lung mechanics. However, neither aerosolized plasminogen activator (PA) yielded durable improvements in physiologic responses or reduction in cast burden. Here, we hypothesized that perfluorochemical (PFC) liquids would facilitate PA distribution and sustain improvements in physiologic outcomes in ISALI. Methods Spontaneously breathing adult sheep (n = 36) received anesthesia and analgesia and were instrumented, exposed to cotton smoke inhalation, and supported by mechanical ventilation for 48 h. Groups (n = 6/group) were studied without supplemental treatment, or, starting 4 h post injury, they received intratracheal low volume (8 mL) PFC liquid alone or a dose range of tPA/PFC or scuPA/PFC suspensions (4 or 8 mg in 8 mL PFC) every 8 h. Outcomes were evaluated by sequential measurements of cardiopulmonary parameters, lung histomorphology, and biochemical analyses of bronchoalveolar lavage fluid. Results Dose‐response and PA‐type comparisons of outcomes demonstrated sustained superiority with low‐volume PFC suspensions of scuPA over tPA or PFC alone, favoring the highest dose of scuPA/PFC suspension over lower doses, without airway bleeding. Conclusions We propose that this improved profile over previously reported aerosolized delivery is likely related to improved dose distribution. Sustained salutary responses to scuPA/PFC suspension delivery in this translational model are encouraging and support the possibility that the observed outcomes could be of clinical importance.

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Section: Methodsmentioning

confidence: 99%

Perfluorochemical‐facilitated plasminogen activator delivery to the airways: A novel treatment for inhalational smoke‐induced acute lung injury

Wolfson

Enkhbaatar

Fukuda

et al. 2020

Clinical & Translational Med

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Nanosystems with potential application as carriers for skin depigmenting actives

Castro,

Pinto,

Dos Santos

et al. 2024

Nanotechnology

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Hyperpigmentation is a skin disorder characterized by excessive production of melanin in the skin and includes dyschromias such as post-inflammatory hyperchromias, lentigens, melasma and chloasma. Topical products containing depigmenting agents offer a less aggressive treatment option for hyperpigmentation compared to methods like chemical peels and laser sessions. However, some of these agents can cause side effects such as redness and skin irritation. Encapsulating these actives in nanosystems shows promise in mitigating these effects and improving product safety and efficacy. In addition, nanocarriers have the ability to penetrate the skin, potentially allowing for targeted delivery of actives to the affected areas. The most commonly investigated nanosystems are nanoemulsions, vesicular nanosystems and nanoparticles, in which different materials can be used to generate different compositions in order to improve the properties of these nanocarriers. Nanocarriers have already been widely explored, but it is necessary to understand the evolution of these technologies when applied to the treatment of skin hyperchromias. Therefore, this literature review aims to present the state of the art over the last 15 years on the use of nanosystems as a potential strategy for encapsulating depigmenting actives for potential application in cosmetic products for skin hyperchromia. By providing a comprehensive overview of the latest research findings and technological advances, this article can contribute to improving the care and quality of life of people affected by this skin condition.

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Repurposing of Plasminogen: An Orphan Medicinal Product Suitable for SARS-CoV-2 Inhalable Therapeutics

et al. 2020

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The SARS-CoV-2 infection is associated with pulmonary coagulopathy, which determines the deposition of fibrin in the air spaces and lung parenchyma. The resulting lung lesions compromise patient pulmonary function and increase mortality, or end in permanent lung damage for those who have recovered from the COVID-19 disease. Therefore, local pulmonary fibrinolysis can be efficacious in degrading pre-existing fibrin clots and reducing the conversion of lung lesions into lasting scars. Plasminogen is considered a key player in fibrinolysis processes, and in view of a bench-to-bedside translation, we focused on the aerosolization of an orphan medicinal product (OMP) for ligneous conjunctivitis: human plasminogen (PLG-OMP) eye drops. As such, the sterile and preservative-free solution guarantees the pharmaceutical quality of GMP production and meets the Ph. Eur. requirements of liquid preparations for nebulization. PLG-OMP aerosolization was evaluated both from technological and stability viewpoints, after being submitted to either jet or ultrasonic nebulization. Jet nebulization resulted in a more efficient delivery of an aerosol suitable for pulmonary deposition. The biochemical investigation highlighted substantial protein integrity maintenance with the percentage of native plasminogen band > 90%, in accordance with the quality specifications of PLG-OMP. In a coherent way, the specific activity of plasminogen is maintained within the range 4.8–5.6 IU/mg (PLG-OMP pre-nebulization: 5.0 IU/mg). This is the first study that focuses on the technological and biochemical aspects of aerosolized plasminogen, which could affect both treatment efficacy and clinical dosage delivery. Increasing evidence for the need of local fibrinolytic therapy could merge with the availability of PLG-OMP as an easy handling solution, readily aerosolizable for a fast translation into an extended clinical efficacy assessment in COVID-19 patients.

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Nebulization of single-chain tissue-type and single-chain urokinase plasminogen activator for treatment of inhalational smoke-induced acute lung injury

Cited by 3 publications

References 79 publications

Perfluorochemical‐facilitated plasminogen activator delivery to the airways: A novel treatment for inhalational smoke‐induced acute lung injury

Perfluorochemical‐facilitated plasminogen activator delivery to the airways: A novel treatment for inhalational smoke‐induced acute lung injury

Nanosystems with potential application as carriers for skin depigmenting actives

Repurposing of Plasminogen: An Orphan Medicinal Product Suitable for SARS-CoV-2 Inhalable Therapeutics

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