Influence of Surface-Modification via PEGylation or Chitosanization of Lipidic Nanocarriers on In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Apixaban

Mohamed F Zaky; Taha M Hammady; Shadeed Gad; Abdullah Alattar; Reem Alshaman; Ann Hegazy; Sawsan A Zaitone; Mamdouh Mostafa Ghorab; Mohamed A Megahed

doi:10.3390/pharmaceutics15061668

Influence of Surface-Modification via PEGylation or Chitosanization of Lipidic Nanocarriers on In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Apixaban

Pharmaceutics. 2023 Jun 7;15(6):1668. doi: 10.3390/pharmaceutics15061668.

Authors

Mohamed F Zaky¹, Taha M Hammady², Shadeed Gad², Abdullah Alattar³, Reem Alshaman³, Ann Hegazy⁴, Sawsan A Zaitone^{3

5}, Mamdouh Mostafa Ghorab², Mohamed A Megahed¹

Affiliations

¹ Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt.
² Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
³ Department of Pharmacology & Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia.
⁴ Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
⁵ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

Abstract

Nanostructured lipid carriers (NLCs) have been proven to significantly improve the bioavailability and efficacy of many drugs; however, they still have many limitations. These limitations could hinder their potential for enhancing the bioavailability of poorly water-soluble drugs and, therefore, require further amendments. From this perspective, we have investigated how the chitosanization and PEGylation of NLCs affected their ability to function as a delivery system for apixaban (APX). These surface modifications could enhance the ability of NLCs to improve the bioavailability and pharmacodynamic activity of the loaded drug. In vitro and in vivo studies were carried out to examine APX-loaded NLCs, chitosan-modified NLCs, and PEGylated NLCs. The three nanoarchitectures displayed a Higuchi-diffusion release pattern in vitro, in addition to having their vesicular outline proven via electron microscopy. PEGylated and chitosanized NLCs retained good stability over 3 months, versus the nonPEGylated and nonchitosanized NLCs. Interestingly, APX-loaded chitosan-modified NLCs displayed better stability than the APX-loaded PEGylated NLCs, in terms of mean vesicle size after 90 days. On the other hand, the absorption profile of APX (AUC_0-inf) in rats pretreated with APX-loaded PEGylated NLCs (108.59 µg·mL^-1·h^-1) was significantly higher than the AUC_0-inf of APX in rats pretreated with APX-loaded chitosan-modified NLCs (93.397 µg·mL^-1·h^-1), and both were also significantly higher than AUC_0-inf of APX-Loaded NLCs (55.435 µg·mL^-1·h^-1). Chitosan-coated NLCs enhanced APX anticoagulant activity with increased prothrombin time and activated partial thromboplastin time by 1.6- and 1.55-folds, respectively, compared to unmodified NLCs, and by 1.23- and 1.37-folds, respectively, compared to PEGylated NLCs. The PEGylation and chitosanization of NLCs enhanced the bioavailability and anticoagulant activity of APX over the nonmodified NLCs; this highlighted the importance of both approaches.

Keywords: PEGylation; apixaban; chitosanization; nanostructured lipid carriers; pharmacokinetics/pharmacodynamics.

Grants and funding

This research received no external funding.