Title : Polymer-modified liposomes as nanocarrier for oral delivery of natural active molecules
Abstract:
Liposomes, with their ability to incorporate molecules of different polarity, are particularly suitable for the delivery of drugs, proteins and other bioactive molecules. Nevertheless, first-generation vesicles suffer from some limitations including physical instability, short in vivo circulation lifetime, reduced payload, uncontrolled release properties, and low targeting abilities. Liposome performance can be improved using both natural and synthetic polymers.
In this study, we exploited polymer-liposomes hybrid system for the oral delivery of natural active molecules. Specifically, we used curcumin, a natural hydrophobic compound with antioxidant, anti-inflammatory and antimicrobial properties but that shows low aqueous solubility and therefore very poor bioavailability, in vivo instability, and rapid metabolism. Therefore, encapsulation of curcumin in liposomes adapted for oral delivery could be a valid approach to protect it from degradation in the gastrointestinal tract (GIT) and promote its absorption. This work illustrates how it is possible to adapt liposomes to oral delivery of curcumin by modulating their composition and coupling them to a suitable polymeric cover. In particular liposomes prepared by micelle-to-vesicle transition method were coated with the pH-sensitive polymer Eudragit S100 using a pH-driven and organic solvent-free method.
The maximum EE% obtained was around 98%. Liposomes were very stable, showing a low tendency to aggregate both at 4 ° C and 25 ° C. The antioxidant and release properties have proved excellent, with a TEAC comparable with that of free curcumin and a cumulative release complete after 200 min. TEM investigations revealed that the Eudragit S100 coating includes several liposomes into clusters of variable shape and size. Prepared vesicles are able to enter in Caco-2 cells through a mechanism of endocytosis where they exert a protective action against oxidative stress as proved by in vitro tests. Liposomes with a double polymer shell were also prepared to gain mucus penetrating and bile salts resistant features in GIT. Vesicles were covered with a first polymer shell of PEG-2000 and then with a second shell of Eudragit-S100. In silico investigations have been conducted to optimize the encapsulation efficiency (EE%) and the loading capacity (LC%) of the curcumin in these conditions. In vitro simulated saliva-gastrointestinal digestion of such systems was performed.
