Preparation, Drug Distribution, and In Vivo Evaluation of the Safety of Protein Corona Liposomes for Liraglutide Delivery

Abstract

The development of oral drug delivery systems is challenging, and issues related to the mucus layer and low intestinal epithelial permeability have not yet been surmounted. The purpose of this study was to develop a promising formulation that is more adapted to in vivo absorption and to facilitate the administration of oral liraglutide. Cationic liposomes (CLs) linked to AT-1002 were prepared using a double-emulsion method, and BSA was adsorbed on the surface of the AT-CLs, resulting in protein corona cationic liposomes with AT-1002 (Pc-AT-CLs). The preparation method was determined by investigating various process parameters. The particle size, potential, and encapsulation efficiency (EE%) of the Pc-AT-CLs were 202.9 ± 12.4 nm, 1.76 ± 4.87 mV, and 84.63 ± 5.05%, respectively. The transmission electron microscopy (TEM) imaging revealed a nearly spherical structure of the Pc-AT-CLs, with a recognizable coating. The circular dichroism experiments confirmed that the complex preparation process did not affect the secondary structure of liraglutide. With the addition of BSA and AT-1002, the mucosal accumulation of the Pc-AT-CLs was nearly two times lower than that of the AT-CLs, and the degree of enteric metaplasia was 1.35 times higher than that of the PcCLs. The duration of the intestinal absorption of the Pc-AT-CLs was longer, offering remarkable biological safety.

Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions

“…Indeed, treatment of epithelial or endothelial cells with AT-1002 led to increased permeability by reversible opening of TJs [ 230 , 231 ]. Since its discovery, AT-1002 has become an important permeability-modulating component in drug development that can be used to increase the absorption and distribution of other drugs [ 230 , 232 ]. Several studies showed that AT-1002 can be used to increase intestinal, intranasal, intratracheal, or transdermal penetration of various compounds improving their bioavailability [ 233 ].…”

Concept for a Unidirectional Release Mucoadhesive Buccal Tablet for Oral Delivery of Antidiabetic Peptide Drugs Such as Insulin, Glucagon-like Peptide 1 (GLP-1), and their Analogs

“…Hence, to overcome potential challenges arising from excessive positive charge, CLs can be modified by coating them with negatively charged materials, thereby reducing their net positive charge. For instance, Ding et al developed protein corona liposomes (Pc-CLs) for oral liraglutide delivery [ 77 ]. They prepared CLs using distearoylphosphatidylcholine (DSPC), Chol-PEG-AT-1002 by the double-emulsion method.…”

“…BSA was then adsorbed onto the surface of the CLs to form Pc-CLs. After BSA adsorption, Pc-CLs’ diameter increased from 127 nm to 202 nm, and the zeta potential decreased from +36.1 to 1.76 [ 77 ]. Insulin was loaded into the Pc-CLs using electroporation.…”

“…Insulin was loaded into the Pc-CLs using electroporation. The encapsulation efficiency and loading capacity of insulin in Pc-CLs were 84.63% and 2.08%, respectively [ 77 ]. These Pc-CLs demonstrated a significant improvement in mucus-penetrating velocity compared to native CLs.…”

Advanced Nanomaterials in Biomedical Application

“…Ding et al [ 13 ] designed protein corona cationic liposomes (CLs) with AT-1002 (TJ regulatory peptide) possessing a core–shell structure based on the characteristics of BSA. Liraglutide was effectively encapsulated in the CLs, with the drug EE% of the liposomes equaling 85 ± 5% and the average particle size equal to 203 ± 13 nm.…”