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06 Feb 2024

Cyclosporine A micellar nasal spray characterization and antiviral action against SARS-CoV-2

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The upper respiratory tract serves as the primary gateway for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections to infiltrate the respiratory system, leading to the development of severe respiratory illnesses. In response to this critical challenge, researchers have undertaken an innovative approach by developing α-tocopheryl-polyethylene-glycol succinate (TPGS) micelles loaded with cyclosporine A (CSA) for nasal administration. This study aims to evaluate the effectiveness of these micellar formulations in preventing and treating SARS-CoV-2 infections during the early stages, focusing on their stability, mucopenetration capabilities, spray characteristics, and antiviral activity.

To ensure the suitability of the micellar formulation for nasal delivery, researchers first assessed its stability and mucopenetration rate in the presence of simulated nasal mucus. The results revealed the formulation’s remarkable long-term stability, a crucial attribute for drug delivery systems. Additionally, the micelles exhibited fast diffusion across the glycoproteins matrix present in the nasal mucus. This indicates that the TPGS micelles loaded with CSA can efficiently traverse the nasal mucosal barrier, potentially improving drug delivery to the upper respiratory tract.

The study further investigated the spray characteristics of the micellar formulation and its deposition profile within a silicon nasal model. Three distinct nasal spray devices were employed to analyze the delivery efficiency. Remarkably, the research identified the nasal spray pump from BiVax, Aptar, as the most effective in providing uniform and widespread deposition throughout the nasal cavity. This finding highlights the significance of selecting an appropriate nasal delivery device for enhancing the therapeutic outcomes of nasal spray formulations.

One of the pivotal aspects of this study was evaluating the antiviral efficacy of CSA-loaded micelles against SARS-CoV-2, particularly the Omicron BA.1 variant. Vero E6 cells were utilized in experiments mimicking treatment scenarios before, during, and after viral infection within the upper respiratory tract. Strikingly, complete viral inactivation was observed when using the CSA-loaded micelles, demonstrating their potent antiviral properties. In contrast, the non-formulated CSA exhibited only minimal antiviral activity. This stark contrast underscores the synergistic effect of the drug and the micellar formulation in combating SARS-CoV-2 infections.

This research showcases the potential clinical efficacy of α-tocopheryl-polyethylene-glycol succinate (TPGS) micelles loaded with cyclosporine A (CSA) as a nasal spray delivery system for the prevention and treatment of SARS-CoV-2 infections. The combination of long-term stability, efficient mucopenetration, and potent antiviral activity against the Omicron BA.1 variant suggests that these micellar formulations have the capacity to be highly effective against a broad spectrum of coronavirus variants. This innovative approach represents a promising step forward in the ongoing battle against COVID-19 and other respiratory infections.

This research presents an exciting development in the field of nasal spray delivery systems, offering a potential solution to combat SARS-CoV-2 infections during the early stages of respiratory tract invasion. The stability, mucopenetration capabilities, and impressive antiviral activity of CSA-loaded micelles hold promise for future clinical applications, offering hope for the effective prevention and treatment of a wide range of coronavirus variants.

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