Platelet directed lectin-conjugated lipid nanocarriers for ticagrelor oral delivery: Development and evaluation

• Published in: Journal of drug delivery science and technology 2025-01, Vol.103, p.106433, Article 106433
• Main Authors: Abdel-Azeem, Mohamed Nabil, Mohamed, Magdy Ibrahim, Akl, Mohamed A.
• Format: Article
• Language: English
• Subjects: Antiplatelet activity; Bioavailability; Central composite design; Lectin; Lipid nanocarriers; Ticagrelor
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2024.106433

Oral delivery of biopharmaceutical classified IV drugs has a great challenge despite the most convenient route of drug administration. Ticagrelor hydrophobicity properties and non-pKa values within the physiological environment lead to poor solubility and permeability. In the last two decades, ligand-conjugated nanocarriers have emerged to increase the effectiveness and safety of such pharmacotherapeutic agents. This research aimed to study the effect of lectin-conjugated lipid nanocarriers on improving oral bioavailability and antiplatelet activity of ticagrelor. Lipid nanocarriers were prepared using the hot emulsification–ultrasonication technique and were optimized using central composite design. Lectin was subsequently conjugated onto the lipid nanocarriers using carbodiimide chemistry. Non-conjugated and conjugated lipid nanocarriers were characterized for encapsulation efficiency, particle size, size distribution, zeta potential, and drug release. Oral bioavailability and targeting efficiency were evaluated. Results of the study showed that the surface-modified lipid nanocarriers had oral bioavailability 2.37 fold higher than free ticagrelor. Furthermore, Lectin-conjugated lipid nanocarriers accumulated more at the thrombus-modified site and less in the liver tissue compared to the non-conjugated nanocarriers and free ticagrelor. [Display omitted]