Evaluation of the Pharmacokinetic parameters of Imatinib lipid nanoparticles modified with HER2 aptamer

Abstract

Breast cancer is one of the top five causes of death in women globally. Current treatment options for various breast cancer subtypes are based on the molecular categorization of the malignant cells. Although imatinib is expected to inhibit breast cancer, its therapeutic effectiveness is limited by off-target cardiotoxicity. Lipid nanoparticles (liposomes and SLNs) have great potential for the delivery of anti-cancer agents due to their rapid uptake, biodegradability. Aptamers can to improve the therapeutic potential of pharmaceuticals by serving as a targeted delivery vehicle. Purposes: This research aimed to design and formulate Her2 aptamer modified lipid nanoparticles loaded with IMT and evaluate in vitro characteristics such as particle size, polydispersity index, zeta potential, encapsulation performance, release performance, stability, and cytotoxicity. and investigating the pharmacokinetic parameters of the prepared formulations in Sprague–Dawley (SD rats ) orthotopic model. Methods: Aptamer modifed Lipid nanoparticles (SLNs and liposomes) were prepared, evaluateted and the Pharmacokinetic parameters of each formulation has been studied. Results: The Aptamer modified lipis nanoparticles showed an average size of 101.6 ± 50.80 nm with a zeta potential value of -19.66 ± 0.55 mV, a PDI of 0.250 and 81.96% ± 0.98% drug entrapment efficiency, meanwhile displayed a sustained release profile Following intravenous administration to rats, APT-IM-LIP not only extended the half-life of IMT, but also prolonged retention of IMT compared with plain IMT after intravenous administration.Conclusion: The study shows potential applications of the aptamerModified lipid nanparticles for active delivery of IMT and the method for the development of LNPs in sustained release of IM for better therapeutic outcomes. Conclusively, the prepared IMT-LNPs were well designed in nanosized ranges and may be a promising formulation for active targeting of IMT.Pharmacokinetic parameters pointed out the potential of formulations for Her2 positive breast cancer cells.