Oral delivery of all-trans retinoic acid mediated by liposome carriers

All-trans retinoic acid (ATRA) is a molecule that finds wide applications in medicine. Connection between cancer cell proliferation and ATRA is a well-established item. Driven by the potential applications of liposomes in stabilizing and protecting therapeutic compounds thus enabling effective delivery of encapsulated compounds, recent research efforts have been directed to understanding mechanisms of oral delivery through the gastrointestinal tract. The surface charge of the liposome bilayers can modify the interactions between the aggregates and the gastrointestinal fluids. Here, we investigated the ability of cationic and anionic liposomes to encapsulate, protect and deliver ATRA in an in-vitro digestion process as a different oral administration route. Stability and encapsulation efficiency of ATRA in negatively and positively charged liposomes enriched with ?-tocopherol were investigated by means of UV?vis spectroscopy, dynamic light scattering and ?-potential. The applicability of the carriers was tested by means of an in-vitro digestion procedure allowing for the measurement of the bioavailability of ATRA. From this study evidence was provided that the water insoluble molecules, ATRA and ?-tocopherol are intercalated in liposome membranes regardless of the surface charge of the vesicle bilayers. Comparisons between cationic and anionic liposomes incorporating retinoic acid show differences in bioavailability. The cationic vesicles are preferable for a larger amount of ATRA bioavailability, which can be understood from electrostatic interactions. Thus ATRA is ionized in a wide range of pHs but protonated in anionic vesicles.

Automated summary

This study investigated the ability of cationic and anionic liposomes to encapsulate, protect, and deliver ATRA in an in-vitro digestion process, showing that cationic vesicles are preferable for higher bioavailability of ATRA.