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In vivo Pharmacokinetics and in vitro Release of Imatinib Mesylate-Loaded Liposomes for Pulmonary Delivery

Authors Xu H, Ji H, Li Z, Qiao W, Wang C, Tang J

Received 29 November 2020

Accepted for publication 11 January 2021

Published 16 February 2021 Volume 2021:16 Pages 1221—1229


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Yan Shen

Hongfei Xu,1,* Hongyu Ji,1,2,* Zerong Li,1,3 Wenmei Qiao,1,4 Chenghao Wang,1 Jingling Tang1

1Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, People’s Republic of China; 3Department of Pharmacy, The Second People’s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518028, People’s Republic of China; 4Department of Pharmacy, Shenzhen Luohu Hospital Group-Shenzhen Luohu Traditional Chinese Medicine Hospital, Shanghai University of Traditional Chinese Medicine-Shenzhen Hospital, Shenzhen, 518001, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jingling Tang
Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, People’s Republic of China
Tel +86-0451-86660103
Fax +86-0451-86664073

Background: Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of vascular endothelial and smooth muscle cells and causes occlusion of pulmonary arterioles that eventually results in right heart failure and death. The platelet-derived growth factor (PDGF) plays a prominent role in abnormal remodeling of pulmonary resistance vessels. Imatinib mesylate (IM), a PDGF-receptor tyrosine kinase inhibitor, was able to ameliorate PAH by reversing pulmonary vascular remodeling.
Methods: In the present study, IM-loaded liposomes (IM-LPs) were developed and administered via the pulmonary route to delay the drug release and improve patient compliance for the treatment of PAH. The IM-LPs were prepared by the transmembrane gradient method with the spherical vesicles. The compatibility of the IM-LPs was studied by determining the viability of pulmonary arterial smooth muscle cells (PASMCs). Particle uptake by rat PASMCs was evaluated by incubating the particles with rat PASMCs. Pharmacokinetic studies were performed in male SD rats.
Results: The IM-LPs 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. Liposomes obviously increased intracellular accumulation of Rhodamine B by PASMCs using the fluorescence microscopic. Following intratracheal administration to rats, IM-LPs not only extended the half-life of IM, but also prolonged retention of IM compared with plain IM solution after intratracheal and intravenous administration.
Conclusion: The study show potential applications of the LPs for pulmonary delivery of IM and the method for the development of LPs in sustained release of IM for better therapeutic outcomes. Conclusively, the prepared IM-LPs were well designed in nanosized ranges and may be a promising formulation for pulmonary delivery of IM.

Keywords: imatinib mesylate, pulmonary arterial hypertension, liposomes, pulmonary delivery, pharmacokinetics

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