Title:Construction and Evaluation of Liraglutide Delivery System based on Milk
Exosomes: A New Idea for Oral Peptide Delivery
Volume: 23
Issue: 8
Author(s): Yanan Shi*, Shiqi Guo, Yanzi Liang, Lanze Liu, Aiping Wang, Kaoxiang Sun and Youxin Li*
Affiliation:
- College of Life Science, Yantai University, Yantai, 264005, P.R. China
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, P.R. China
- State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharmaceutical Co., Ltd., Yantai, China
Keywords:
Milk exosomes, liraglutide, oral delivery system, nanovesicle, peptide-carrying exosomes, dialysis bag.
Abstract:
Background: Increasing the bioavailability of peptide or protein drugs have always
been an important topic in the field of pharmacy. Milk exosomes as a carrier for oral drug
delivery systems have begun to attract attention in recent years. The application of oral milk
exosomes carriers to peptide drugs, such as liraglutide, is worth trying.
Objectives: Milk-derived exosomes are used in this study to try to encapsulate the GLP-1
receptor agonist liraglutide and the feasibility of using this drug delivery system for oral
biomolecules delivery in the future is explored.
Methods: The size and morphology of milk exosomes were characterized. The gastrointestinal
stability of milk exosomes was evaluated in a dialysis bag. The cellular uptake of milk
exosomes in the intestinal cells was observed. Six drug loading methods have been evaluated
and compared preliminarily and they are incubation method, sonication method, extrusion
method, freeze-thaw cycles method, saponin-assisted method and electroporation method.
Results: As demonstrated in this study, milk exosomes showed significant stability in the
gastrointestinal environment and excellent affinity with intestinal cells, indicating their unique
benefits used for drug oral delivery. Effective drug loading method for exosomes is challenging.
Among the six drug loading methods used in this study, the liraglutide-Exo prepared by the
extrusion method obtained the largest drug load, which was 2.45 times the direct incubation
method. The liraglutide-Exo obtained by the freeze-thaw cycles method has the smallest
morphological change.
Conclusion: The study showed that milk exosome-based oral drug delivery systems are
promising.