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Liposomes as delivery system

HOME \ Liposomes as delivery system

Benefits of liposomes as delivery system

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Liposomes

”Liposome application as nutraceuticals is currently rapidly evolving, mainly inspired by the possibility that liposomal incorporation can enhance the often poor uptake of nutraceutical compounds into the bloodstream after oral intake.”

Liposomes can act as delivery vehicles for a wide spectrum of bioactive compounds [1,2]. Liposomes are small spherical vesicles consisting of one or more membranes surrounding aqueous compartments. Structurally, these membranes consist of bilayers of phospholipids, natural molecules which are also the main component of human cell membranes. Because of the presence of a water as well as a lipid compartment within one liposome particle, both water soluble  and poorly water soluble compounds can be incorporated in liposomes. Until recently, the use of liposomes in medicine was mainly restricted to their use as pharmaceuticals. Their application as nutraceuticals is currently  rapidly evolving, mainly inspired by the possibility that liposomal incorporation can enhance the often poor uptake of nutraceutical compounds into the bloodstream after oral intake.

Liposome structure

Advantages of liposomal nutraceuticals

”The encapsulation of bioactive compounds in liposomes is attractive as liposomes have been shown to be able to overcome serious hurdles actives would otherwise encounter in the gastrointestinal tract”

Liposomal nutraceuticals contain bioactive compounds with health-promoting effects. The encapsulation of bioactive compounds in liposomes is attractive as liposomes have been shown to be able to overcome serious hurdles bioactives would otherwise encounter in the gastrointestinal (GI) tract upon oral intake [5]. Poor water solubility and degradation during their passage through the GI tract are often strongly limiting the entry of these compounds into the bloodstream. Liposome encapsulation can increase the arrival of such compounds in the blood circulation (bioavailability) by providing solubilization and protection. The exact mechanisms by which liposomes are able to increase the bioavailability of such compounds are still further investigated. As liposomes are composed of building blocks that are also naturally occurring as major components of cell membranes in the human body, they are biodegradable and safe for oral use.

Benefits of Phospholipids as building blocks

”Phospholipids are vital to physiological processes and healthy organ function”

Phospholipids are the fundamental building blocks of cell membranes and liposomes. They have a polar, hydrophilic head group and two hydrophobic tails, which are usually fatty acids. They are essential for the formation of the liposomal vesicles for the delivery of bioactive compounds. They also have health benefits themselves. For example, they are required for the assembly and secretion of lipoproteins that transport lipids and cholesterol through the bloodstream. Furthermore, maintaining proper levels and ratios of phospholipid types is vital for healthy organ function [21]. Health effects of dietary phospholipids have been reported in many studies, as exemplified by scientific literature pointing to beneficial effects regarding inflammation [6-12], liver health [13-15], fatigue reduction [16] and brain function [17-20]. Phospholipids like PC and PE naturally occur in several dietary sources such as egg, soybeans and milk [21]. Being composed of phospholipids, our liposomes are fully biologically degradable.

Sources

[1] Filipczak, N., Pan, J., Yalamarty, S., & Torchilin, V. P. (2020). Recent advancements in liposome technology. Advanced drug delivery reviews, 156, 4–22.  

[2] Crommelin, D., van Hoogevest, P., & Storm, G. (2020). The role of liposomes in clinical nanomedicine development. What now? Now what?. Journal of controlled release : official journal of the Controlled Release Society, 318, 256–263.  

[3] DeFelice SL. The nutraceutical revolution: its impact on food industry R&D. Trends Food Sci Technol 1995; 6: 59–61.

[4] Santini, A., Cammarata, S. M., Capone, G., Ianaro, A., Tenore, G. C., Pani, L., & Novellino, E. (2018). Nutraceuticals: opening the debate for a regulatory framework. British journal of clinical pharmacology, 84(4), 659–672. 

[5] Porter, C,J,, Trevaskis, N.L., Charman, W.N. (2007). Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nature Reviews Drug Discovery 6(3), 231-48.

[6] Detopoulou, P., Panagiotakos, D. B., Antonopoulou, S., Pitsavos, C., & Stefanadis, C. (2008). Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study. The American journal of clinical nutrition, 87(2), 424-430.

[7] Ehehalt, R., Wagenblast, J., Erben, G., Lehmann, W. D., Hinz, U., Merle, U., & Stremmel, W. (2004). Phosphatidylcholine and lysophosphatidylcholine in intestinal mucus of ulcerative colitis patients. A quantitative approach by nanoelectrospray‐tandem mass spectrometry. Scandinavian journal of gastroenterology, 39(8), 737-742.

[8] Braun, A., Treede, I., Gotthardt, D., Tietje, A., Zahn, A., Ruhwald, R., Schoenfeld, U., Welsch, T., Kienle, P., Erben, G., Lehmann, W.D., Fuellekrug, J., Stremmel, W., Ehehalt, R. (2009). Alterations of phospholipid concentration and species composition of the intestinal mucus barrier in ulcerative colitis: a clue to pathogenesis. Inflammatory Bowel Diseases, 15(11), 1705-1720.

[9] Stremmel, W., Merle, U., Zahn, A., Autschbach, F., Hinz, U., Ehehalt, R. (2005). Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis. Gut, 54(7), 966-971.

[10] Stremmel, W., Ehehalt, R., Autschbach, F., Karner, M. (2007). Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Annals of Internal Medicine, 147(9), 603-610.

[11] Stremmel, W., Braun, A., Hanemann, A., Ehehalt, R., Autschbach, F., Karner, M. (2010). Delayed release phosphatidylcholine in chronic-active ulcerative colitis: a randomized, double-blinded, dose finding study. Journal of Clinical Gastroenterology, 44(5), e101-e107.

[12] Karner, M., Kocjan, A., Stein, J., Schreiber, S., von Boyen, G., Uebel, P., Schmidt, C., Kupcinskas, L., Dina, I., Zuelch, F., Keilhauer, G., Stremmel, W. (2014). First multicenter study of modified release phosphatidylcholine “LT-02” in ulcerative colitis: a randomized, placebo-controlled trial in mesalazine-refractory courses. American Journal of Gastroenterology, 109(7), 1041-1051.

[13] Li, Z., Agellon, L.B., Allen, T.M., Umeda, M., Jewell, L., Mason, A., Vance, D.E. (2006). The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metabolism, 3(5), 321-31.

[14] Puri, P., Baillie, R.A., Wiest, M.M., Mirshahi, F., Choudhury, J., Cheung, O., Sargeant, C., Contos, M.J., Sanyal, A.J. (2007). A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology, 46(4), 1081-1090.

[15] Nicolson, G. L., & Ash, M. E. (2017). Membrane Lipid Replacement for chronic illnesses, aging and cancer using oral glycerolphospholipid formulations with fructooligosaccharides to restore phospholipid function in cellular membranes, organelles, cells and tissues. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1859(9), 1704-1724.

[16] Hirose, A., Terauchi, M, Osaka, Y., Akiyoshi, M., Kato, K., Miyasaka, N. (2018). Effect of soy lecithin on fatigue and menopausal symptoms in middle-aged women: a randomized, double-blind, placebo-controlled study. Nutrition Journal, 17(1), 1-8. 

[17] Lieber, C.S., Robins, S.J., Li, J., DeCarli, L.M., Mak, K.M., Fasulo, J.M., Leo, M.A. (1994). Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology, 106(1), 152-159.

[18] Poly, C., Massaro, J.M., Seshadri, S., Wolf, P.A., Cho, E., Krall, E., Jacques, P.F., Au, R. (2011). The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. The American Journal of Clinical Nutrition, 94(6), 1584-1591. 

[19] Suzuki, S., Yamatoya, H., Sakai, M., Kataoka, A., Furushiro, M., Kudo, S. (2001). Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats. The Journal of Nutrition, 131(11), 2951-2956.

[20] Lee, B., Sur, B.J., Han, J.J., Shim, I., Her, S., Lee, Y.S., Lee, H.J., Hahm, D.H. (2015). Oral administration of squid lecithin-transphosphatidylated phosphatidylserine improves memory impairment in aged rats. Progress in Neuro-psychopharmacology and Biological Psychiatry, 56, 1-10.

[21] Zhou, M.M., Xue, Y., Sun, S.H., Wen, M., Li, Z.J., Xu, J., Wang, J.F., Yanagita, T., Wang, Y.M., Xue, C.H. (2016). Effects of different fatty acids composition of phosphatidylcholine on brain function of dementia mice induced by scopolamine. Lipids in Health and Disease, 15(1), 1-10. 

[22] Küllenberg, D., Taylor, L.A., Schneider, M., Massing, U. (2012). Health effects of dietary phospholipids. Lipids in Health and Disease, 11(1), 1-16.

Liposomal drug product compared with conventional suspension

This graph outlines the results of an example study in which a liposomal drug product is compared with the drug formulated as a conventional suspension. The results show that with specially engineered liposomal formulations improved drug levels and thus better bioavailability can be achieved in specific cases [22].

Additional liposome studies

Liposome technology

Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S.W., Zarghami, N., Hanifehpour, Y., Samiei, M., Kouhi, M., Nejati-Koshki, K. (2013). Liposome: classification, preparation, and applications. Nanoscale Research Letters 8(1), 102. doi: 10.1186/1556-276X-8-102.

Briuglia, M.L., Rotella, C., McFarlane, A., Lamprou, D.A. (2015). Influence of cholesterol on liposome stability and on in vitro drug release. Drug Delivery and Translational Research 5(3), 231-42. doi: 10.1007/s13346-015-0220-8.

Chen, W., Zou, M., Ma, X., Lv, R., Ding, T., Liu, D. (2019). Co-Encapsulation of EGCG and Quercetin in Liposomes for Optimum Antioxidant Activity. Journal of Food Science 84(1), 111-120. doi: 10.1111/1750-3841.14405.

Kraft, J.C., Freeling, J.P., Wang, Z., & Ho R.J.Y. (2014). Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. Journal of Pharmaceutical Sciences 103(1), 29–52.

Bioavailability of active compounds

Martinez, M.N., Amidon, G.L. (2002). A mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals. Journal of Clinical Pharmacology 42(6), 620-43.

Takahashi, M., Uechi, S., Takara, K., Asikin, Y., & Wada, K. (2009). Evaluation of an Oral Carrier System in Rats: Bioavailability and Antioxidant Properties of Liposome-Encapsulated Curcumin. Journal of Agricultural and Food Chemistry 57(19), 9141–9146.

Wajda, R., Zirkel, J., Schaffer, T. (2007). Increase of bioavailability of coenzyme Q(10) and vitamin E. Journal of Medicinal Food 10(4), 731-4.

DHA

Sun, G. Y., Simonyi, A., Fritsche, K. L., Chuang, D. Y., Hannink, M., Gu, Z., Greenlief, C. M., Yao, J. K., Lee, J. C., & Beversdorf, D. Q. (2018). Docosahexaenoic acid (DHA): An essential nutrient and a nutraceutical for brain health and diseases. Prostaglandins, leukotrienes, and essential fatty acids 136, 3–13. doi: 10.1016/j.plefa.2017.03.006.

Weiser, M. J., Butt, C. M., & Mohajeri, M. H. (2016). Docosahexaenoic Acid and Cognition throughout the Lifespan. Nutrients 8(2), 99. doi: 10.3390/nu8020099.

PEA

Davis, M. P., Behm, B., Mehta, Z., & Fernandez, C. (2019). The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review. The American journal of hospice & palliative care 36(12), 1134–1154. doi: 10.1177/1049909119850807.

Mattace Raso, G., Russo, R., Calignano, A., & Meli, R. (2014). Palmitoylethanolamide in CNS health and disease. Pharmacological research 86, 32–41. doi: 10.1016/j.phrs.2014.05.006.

Lutein

Mares J. (2016). Lutein and Zeaxanthin Isomers in Eye Health and Disease. Annual review of nutrition 36, 571–602. doi: 10.1146/annurev-nutr-071715-051110.

Ranard, K. M., Jeon, S., Mohn, E. S., Griffiths, J. C., Johnson, E. J., & Erdman, J. W., Jr (2017). Dietary guidance for lutein: consideration for intake recommendations is scientifically supported. European journal of nutrition, 56(Suppl 3), 37–42. doi: 10.1007/s00394-017-1580-2.

Melatonin

Andersen, L. P., Werner, M. U., Rosenkilde, M. M., Harpsøe, N. G., Fuglsang, H., Rosenberg, J., & Gögenur, I. (2016). Pharmacokinetics of oral and intravenous melatonin in healthy volunteers. BMC pharmacology & toxicology 17, 8. doi: 10.1186/s40360-016-0052-2.

Meng, X., Li, Y., Li, S., Zhou, Y., Gan, R. Y., Xu, D. P., & Li, H. B. (2017). Dietary Sources and Bioactivities of Melatonin. Nutrients 9(4), 367. doi: 10.3390/nu9040367

CBD

Fraguas-Sánchez, A. I., & Torres-Suárez, A. I. (2018). Medical Use of Cannabinoids. Drugs 78(16), 1665–1703. doi: 10.1007/s40265-018-0996-1.

Lucas, C. J., Galettis, P., & Schneider, J. (2018). The pharmacokinetics and the pharmacodynamics of cannabinoids. British journal of clinical pharmacology 84(11), 2477–2482. doi: 10.1111/bcp.13710.

Pisanti, S., Malfitano, A. M., Ciaglia, E., Lamberti, A., Ranieri, R., Cuomo, G., Abate, M., Faggiana, G., Proto, M. C., Fiore, D., Laezza, C., & Bifulco, M. (2017). Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacology & therapeutics 175, 133–150. doi: 10.1016/j.pharmthera.2017.02.041.

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