LiposomePhospholipids (PL) and especially Phosphatidylcholine (PC) are indispensable molecules for cellular differentiation, proliferation, and regeneration, as well as for the transport of molecules through membranes. They control membrane-dependent metabolic processes between the intracellular and intercellular space, maintain and promote the activity and activation of membrane-bound proteins such as enzymes (e.g., Na_-K_-ATPase, lipoprotein lipase, lecithin cholesterol acyltransferase (LCAT) and cytochrome oxidase) and receptors (e.g., of insulin), and contain bound polyunsaturated fatty acids to be released on demand as precursors of cytoprotective prostaglandins and other eicosanoids. They are a source of second messengers in cell signaling (e.g., of diacylglycerol), contain phosphate for cellular processes including ATP formation, participate in fat emulsification in the gastrointestinal tract and bile, are a determinant of erythrocyte and platelet aggregation, and influence immunological processes at the cellular level.6
Due to the unique characteristics of Phospholipids they may be used as excipients in the formulation of various components to enhance the absorption and bioavailability of active ingredients. In this article we are going to focus specifically on the use of Liposomes as an active delivery system, but the forms and use of phospholipid applications as an active delivery system is very broad indeed.
PL Applications include among others: 5
1. Liposomes
2. Mixed Micelles
3. Emulsions
4. Micro-/Nanoemulsions
5. Self-emulsifying Drug Delivery Systems
6. Solid Lipid Nanoparticles
7. Suspensions
8. Phospholipid-Drug Complexes
Liposomes
A basic liposome is a biological vesicle composed of phospholipids consisting of enriched phosphatidylcholine(PC), and consisting of a hydrophilic head group, and hydrophobic tails that are inherently positioned so that the hydrophobic tails are inside the bilayer. The reason for this formation is that Phospholipids have a unique amphiphilic character 1. When placed in water, they form various structures depending on their specific properties and production methods. Mostly, and without interference, phospholipids form micelles, or are organized as lipid bilayers with the hydrophobic tails lined up against one another and the hydrophilic head-group facing the water on both sides. These unique bilayer features make phospholipids very suitable for use as excipients to increase the absorption of biologically active ingredients in pharmaceutical and nutraceuticals applications 5.
Liposomes work in mysterious ways to increase absorption, but it is most likely that the enhanced solubility of lipophilic actives from phospholipid-based systems are not necessarily the direct result of the administered phospholipid arrangement, but more likely the result of the intra-luminal processing of the active before it gets absorbed.5 Normally, the presence of phospholipids in the gastrointestinal tract induces secretion of gastric lipases, pancreatic lipases and co-lipases, which facilitate a special environment in the gut that activates and promotes better absorption 5.
Liposomes have been known within the scientific community for decades as effective carriers of biologically active ingredients used to target specific sites of action. Today, phospholipids are widely used as active ingredients (i.e. PhosChol), and as pharmaceutical, nutraceutical, and cosmecuetical excipients. Phospholipid based delivery applications become very interesting as they offer many oral and topical applications for phospholipids in general, and purified phosphatidylcholine (PPC) in particular.
Phospholipid based and Liposomal formulations, can be applied to influence the absorption of active ingredients via various mechanisms, such as modifying the release of active ingredients, improving their bioavailability, changing the composition and therefore the character of the intestinal environment, stimulating the lymphatic transport of active ingredients 2, interacting with enterocyte-based transport processes and reducing unwanted side effects. In fact, liposomes have received significant attention for their ability to enhance the permeability of actives across the enterocyte, to stabilize actives, and to provide the opportunity of controlled release and efficacious lymphatic delivery. The benefit of increasing lymphatic delivery of actives and bypassing the liver is a unique characteristic of a targeted liposome delivery system 4.
Phospholipids can also be applied to protect active ingredients from degradation in the gastrointestinal tract. The gastrointestinal tract acts as a physiological and chemical barrier, and presents many challenges for oral delivery systems. The development of more advanced composite phospholipid formulation methods help to improve ingredient targeting and bioavailability, and the future potential of this emerging field in active delivery systems has exciting potential. In this context, a deeper knowledge of phospholipids makes them increasingly interesting for the formulation of primary actives and the formation of solubilized phases, by which further increases in absorption and targeting will occur 2.
Additional advantages of phospholipid formulations in active delivery systems are that ingredients prone to decomposition by enzymes in the GI tract may be protected from degradation by formulation with phospholipids and especially phosphatidylcholine (PC). Another benefit of oral formulations with phospholipids is their ability to diminish the harmful GI side effects of NSAIDs in particular and by other substances (e.g., ethanol, prescription drugs, and environmental chemicals) in general 5.
Liposome technology can be used to convert conventional pills and tablets, into liquids and sublingual sprays, thereby enhancing Tmax and Cpmax and overall bioavailability. The result is enhanced therapeutic outcomes as compared to conventional dosage forms that travel through the digestive tract without the many benefits of a phospholipid presence to promote better absorption.*
Bruce Perry
President, Nutrasal, Inc.


References

1. Daniela Kuellenberg, Lenka A. Taylor, Micheal Schneider, Ulrich Massing, Health effects of Dietary Phospholipids: Lipids in Health and Disease, Lipids in Health and Disease, Jaunary 2012.
2. Caitriona M. O’Driscoll, Lipid-based formulations for intestinal lymphatic delivery: European Journal of Pharmaceutical Sciences, 2002 Jun;15(5):405-15
3. C. M. O’Driscoll, Lymphatic Transport of Drugs: Department of Pharmaceutics, Trinity College, University of Dublin, Ireland. (online publication)
4. Hyeongmin Kim1, Yeongseok Kim1, Jaehwi Lee, Liposomal formulations for enhanced lymphatic drug delivery: Asian Journal of Pharmaceutical Sciences, April 2013.
5. Gert Fricker & Torsten Kromp & Armin Wendel & Alfred Blume & Jürgen Zirkel & Herbert Rebmann & Constanze Setzer & Ralf-Olaf Quinkert & Frank Martin & Christel Müller-Goymann, Phospholipids and Lipid-Based Formulations in Oral Drug Delivery: Pharm Res, April 2010.
6. Karl-Josef Gundermann, Ann Kuenker, Erwin Kuntz, Marek DroŸdzik, Activity of essential phospholipids (EPL) from soybean in liver diseases, Pharmacological Reports, Institute for Pharmacology, Polish Academy of Sciences, 2011


*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.**This blog was written by an outside source. This blog does not necessarily reflect the views or position of Natural Partners.