Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Investigating the Impact of Secukinumab Bulk and Liposome Forms on Lymphocytes from Psoriasis Patients, as Compared to Healthy Controls, to Determine the Improvement in Bioavailability of Secukinumab Nanoliposomes

Version 1 : Received: 7 March 2024 / Approved: 8 March 2024 / Online: 8 March 2024 (15:31:07 CET)

How to cite: Layas, G.; Isreb, M.; Ghaderi, N.; Shahzad, F.; Akhbari, P.; Anderson, D.; Wright, A.; Mojgan Najafzadeh, M. Investigating the Impact of Secukinumab Bulk and Liposome Forms on Lymphocytes from Psoriasis Patients, as Compared to Healthy Controls, to Determine the Improvement in Bioavailability of Secukinumab Nanoliposomes. Preprints 2024, 2024030483. https://doi.org/10.20944/preprints202403.0483.v1 Layas, G.; Isreb, M.; Ghaderi, N.; Shahzad, F.; Akhbari, P.; Anderson, D.; Wright, A.; Mojgan Najafzadeh, M. Investigating the Impact of Secukinumab Bulk and Liposome Forms on Lymphocytes from Psoriasis Patients, as Compared to Healthy Controls, to Determine the Improvement in Bioavailability of Secukinumab Nanoliposomes. Preprints 2024, 2024030483. https://doi.org/10.20944/preprints202403.0483.v1

Abstract

Psoriasis is a multi-factorial immune-mediated disease that affects approximately 2% of the UK population and 2.5% worldwide. The condition can impact multiple organs, including the skin and joints. In moderate to severe cases, systemic and topical medications may not provide adequate relief, and as a result, biologic treatments are often administered as a monotherapy or in combination with other treatments. While biologic treatments are more effective than systemic and topical medications in treating psoriasis, patients require close supervision and monitoring while receiving this type of treatment. Liposomes are highly versatile and can be employed for therapy and research applications. They enhance drug retention at the site of administration, thereby reducing systemic side effects. Our study was the first to investigate the genotoxicity of secukinumab, an ideal biologic treatment for psoriasis (a human IgG1k antibody, anti-IL17A), in bulk and liposome nanoparticles on the lymphocytes of psoriasis patients compared to healthy individuals. We evaluated and com-pared the genotoxicity of secukinumab in bulk and liposomal form using the Comet and micronucleus assays. Both assays demonstrated that secukinumab in both forms did not ex-hibit genotoxicity and reduced DNA damage following treatment of the lymphocytes from healthy individuals and psoriatic patients with secukinumab bulk and liposomes format. Both concentrations of secukinumab used (2.1 and 2.8 µg/mL) effectively decreased H2O2-induced DNA damage in both groups to nearly the level of the negative control. Secukinumab bulk and liposome form significantly decreased H2O2-induced damage and efficiently attenuated its adverse effects both in the Comet (p<0.0001) and micronucleus assays (p<0.01). Overall, secukinumab in both forms exhibited protective and an-ti-genotoxic effects by demonstrating its potential to reduce DNA damage caused by oxida-tive stress and by not inducing any further damage in the lymphocytes of either healthy in-dividuals or patients.

Keywords

Secukinumab; liposome; Psoriasis; Bioavailability; DNA damage

Subject

Medicine and Pharmacology, Dermatology

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