Soy lecithin-based liposomes for lymphatic delivery of biologically active substances

Introduction. The targeted delivery of lipophilic chemotherapeutic and immunomodulatory agents through the lymphatic system is a promising approach in cancer treatment. Lipid-based carriers (e.g., liposomes) are able to not only to enhance the solubility and stability of drugs, but also to ensure their protection from degradation in the gastrointestinal tract. Research into the potential of lymphatic delivery of bioactive substances using liposomes can further improve the effectiveness of lipophilic drugs.

Objective. To study the prospects for using first-generation soy lecithin-based liposomes (cholesterol-free) as a lymphatic carrier for biologically active substances.

Materials and methods. Liposomes were prepared from soy lecithin containing green fluorescent protein GFP (with a maximum fluorescence at a wavelength of 506 nm) using the method of thin-film hydration/rehydration. Some liposomes were modified by 1%, 0.5%, and 0.1% chitosan solutions. The GFP incorporation into the liposomes was visualized using confocal microscopy. In vivo studies were conducted in three groups of female Balb/c mice aged 11–13 weeks (three animals in each): a control group; a group receiving native fluorescent protein, and a group with the design formulation (liposomes containing fluorescent protein). After intake, the small intestine was retrieved followed by its preparation and cryosection staining. The analysis of the cell suspension was performed using a CytoFLEX V5-B5-R3 flow cytometer.

Results. The confocal microscopy study found the particle size of the liposomes obtained by the thin-film hydration method to range within 1–5 μm. The incorporation of the model protein into the liposomes, as evidenced by its content before and after the liposome formation, was at least 60%. In vivo experiments on mice found that intragastric administration of fluorescent protein-containing liposomes enables successful protein delivery to the intestinal wall.

Conclusions. Soy lecithin-based liposomes were obtained using the thin-film hydration method. Confocal microscopy was used to evaluate the size of the obtained liposomes and to assess qualitatively the incorporation of green fluorescent protein. The incorporation of chitosan into the liposome shell resulted in a significant aggregation of the final product, which may reduce the effectiveness of liposome delivery to cells. Confocal microscopy of cryosections and cytofluorometry of cell suspensions obtained from small intestine fragments showed the capacity of the engineered system to deliver fluorescent protein and, possibly, intact liposomes to the intestinal wall.

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