OX26-cojugated gangliosilated liposomes to improve the post-ischemic therapeutic effect of CDP-choline

Nicola d'Avanzo; Donatella Paolino; Antonella Barone; Luigi Ciriolo; Antonia Mancuso; Maria Chiara Christiano; Anna Maria Tolomeo; Christian Celia; Xiaoyong Deng; Massimo Fresta

doi:10.1007/s13346-024-01556-3

OX26-cojugated gangliosilated liposomes to improve the post-ischemic therapeutic effect of CDP-choline

Drug Deliv Transl Res. 2024 Mar 13. doi: 10.1007/s13346-024-01556-3. Online ahead of print.

Authors

Affiliations

¹ Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Viale "S. Venuta", 88100, Catanzaro, Italy.
² Department of Health Sciences, University of Catanzaro "Magna Graecia", Viale "S. Venuta", 88100, Catanzaro, Italy.
³ Department of Medical and Surgical Sciences, University of Catanzaro "Magna Graecia", Viale "S. Venuta", 88100, Catanzaro, Italy.
⁴ Department of Cardiac, Thoracic and Vascular Science and Public Health, University of Padova, 35128, Padua, Italy.
⁵ Perdiatric Research Institute "Città della Speranza", Corso Stati Uniti, 4, 35127, Padua, Italy.
⁶ Department of Pharmacy, University of Chieti - Pescara "G. d'Annunzio", Via dei Vestini 31, 66100, Chieti, Italy. c.celia@unich.it.
⁷ Lithuanian University of Health Sciences, Laboratory of Drug Targets Histopathology, Institute of Cardiology, A. Mickeviciaus g. 9, LT-44307, Kaunas, Lithuania. c.celia@unich.it.
⁸ Institute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China. c.celia@unich.it.
⁹ Institute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China. xydeng@shu.edu.cn.
¹⁰ Department of Health Sciences, University of Catanzaro "Magna Graecia", Viale "S. Venuta", 88100, Catanzaro, Italy. fresta@unicz.it.

^# Contributed equally.

PMID: 38478324
DOI: 10.1007/s13346-024-01556-3

Abstract

Cerebrovascular impairment represents one of the main causes of death worldwide with a mortality rate of 5.5 million per year. The disability of 50% of surviving patients has high social impacts and costs in long period treatment for national healthcare systems. For these reasons, the efficacious clinical treatment of patients, with brain ischemic stroke, remains a medical need. To this aim, a liposome nanomedicine, with monosialic ganglioside type 1 (GM1), OX26 (an anti-transferrin receptor antibody), and CDP-choline (a neurotrophic drug) (CDP-choline/OX26Lip) was prepared. CDP-choline/OX26Lip were prepared by a freeze and thaw method and then extruded through polycarbonate filters, to have narrow size distributed liposomes of ~80 nm. CDP-choline/OX26Lip were stable in human serum, they had suitable pharmacokinetic properties, and 30.0 ± 4.2% of the injected drug was still present in the blood stream 12 h after its systemic injection. The post-ischemic therapeutic effect of CDP-choline/OX26Lip is higher than CDP-choline/Lip, thus showing a significantly high survival rate of the re-perfused post-ischemic rats, i.e. 96% and 78% after 8 days. The treatment with CDP-choline/OX26Lip significantly decreased the peroxidation rate of ~5-times compared to CDP-choline/Lip; and the resulting conjugated dienes, that was 13.9 ± 1.1 mmol/mg proteins for CDP-choline/Lip and 3.1 ± 0.8 for CDP-choline/OX26Lip. OX26 increased the accumulation of GM1-liposomes in the brain tissues and thus the efficacious of CDP-choline. Therefore, this nanomedicine may represent a strategy for the reassessment of CDP-choline to treat post-ischemic events caused by brain stroke, and respond to a significant clinical need.

Keywords: Brain targeting; CDP-choline; Liposomes; Nanomedicine; Stroke.