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ADVANCED LIPID FORMULATIONS FOR ORAL DELIVERY
Advanced lipid formulations contain bioactive compounds with health-promoting effects. These compounds are encapsulated in liposomes or NLCs to enable them to overcome serious hurdles they would otherwise encounter in the gastrointestinal (GI) tract upon oral intake [1,2]. Liposomes and NLCs are particularly useful for the delivery of bioactive compounds with a molecular structure that is hydrophobic (i.e. ‘water fearing’). Their hydrophobic nature is the reason why such compounds are poorly soluble in aqueous media including GI fluids, making low solubility the first hurdle to be overcome. Also, prior to absorption into the bloodstream, hydrophobic bioactives must resist degradation due to the harsh conditions in the GI tract. Finally, they face the low permeability of the GI tract wall. Next to hydrophobic compounds, liposomes can encapsulate hydrophilic actives as well.
LIPOSOME AND NLC TECHNOLOGY
Despite most marketing claims, these problematic factors make it unlikely for many nutraceuticals and drug substances to reach their full potential without proper delivery. LIPOSOMA’s solution is to exploit liposomal and other technologies for this delivery purpose. LIPOSOMA’s well-developed and well-characterized liposomal and NLC technology allows for stable encapsulation and optimal delivery, maximizing the chance of achieving the intended physiological effects and health benefits.
INNOCUOUS NATURE & STRUCTURAL VERSATILITY
Over the years, a large variety of delivery systems have been reported. Of these, most excitement has been engendered by the liposome system [3,4]. Liposomes are very small (usually smaller than 1 micrometer) spherical vesicles made of phospholipid bilayers enclosing an aqueous interior. Liposomes are suitable for loading poorly water-soluble compounds (within the bilayer membranes) as well as water-soluble compounds (within the internal aqueous cavity). Phospholipids are also naturally occurring as major components of cell membranes in the human body. They render liposomes biodegradable and safe for oral and parenteral use by humans. Structural versatility in terms of size, charge and lipid composition is another important feature of liposomal formulations, allowing optimal tailoring to the type of bioactive that needs to be incorporated. Thanks to their structure, liposomes also have the potential to deliver more than one bioactive compound via co-encapsulation.
Solubilization of poorly water-soluble bioactive compounds
Many natural bioactive compounds are poorly water soluble (often termed hydrophobic meaning ‘water fearing’). This property is usually strongly limiting their administration and in the case of oral administration, with inferior bioactivity as a consequence. Liposomes offer the opportunity to solubilize such compounds in their phospholipid bilayers and to enhance their transport over the GI tract wall [5]. Once trapped in this hydrophobic bilayer environment, the compounds are well accommodated by the liposomes as they avoid the water molecules in the surrounding aqueous medium. NLCs can encapsulate hydrophobic compounds in their lipid core and keep them in amorphous state, thereby preventing their crystallisation and precipitation and enhancing the absorption and bioavailability of the actives.
Protection of encapsulated bioactive compounds
Bioactive compounds may be metabolized by different enzymes or undergo chemical degradation (e.g. hydrolysis and oxidation) during their passage through the GI tract before reaching the epithelium cells in the GI tract wall [1]. Obviously, the occurrence of such processes translates into a loss of the amount of the active ingredient which can be absorbed into the bloodstream. Encapsulation in liposomes or NLCs can protect bioactive compounds against such detrimental processes [2-5].
Robust liposome production technology
Liposomes have matured as a delivery system for therapeutic agents, as evidenced by the availability of quite some pharmaceutical liposome products in important disease areas in the clinic [7]. Currently, we see a wave of new liposomal products entering the field of nutraceuticals and food supplements. Despite this progress, it is important to realize that the production of liposomal pharmaceuticals and nutraceuticals is certainly not without challenges [8]. Solidly grounded in scientific research and with broad expertise in manufacturing and quality control, LIPOSOMA is the optimal partner for anyone with the ambition to investigate, develop and/or produce liposomal health products.
ENHANCED BIOAVAILABILITY WITH ORAL ADMINISTRATION
The above mentioned hurdles can strongly limit the entry of the orally administered nutraceuticals into the blood circulation. Poor absorption from the GI tract lumen results in low bioavailability (i.e. the amount reaching the bloodstream) of the compound and therefore low bioactivity. It is well documented that liposome or NLC encapsulation can increase the bioavailability of bioactive compounds with low water solubility [2,5]. Liposomal oral delivery can also improve the body distribution of a lipophilic active molecule after the process of intestinal uptake, by locally stimulating the production of so-called chylomicrons (small fat particles) that enter the lymphatic system instead of the blood circulation. This way, rapid deactivation of the bioactive by the liver enzymes can be avoided [6]. Moreover, liposomal redirection of the actives after uptake protects the active substance from rapid clearance. Many active substances that are administered in the traditional manner are simply lost because following absorption they are led straight to the liver (the ‘hepatic portal system’). The liver breaks down the active substance before it has the chance to reach the target cells. Liposomal encapsulation can help prevent this loss [5,6].
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].
VITAMIN C
Another study has shown that the intravenous administration of liposomal vitamin C leads to the highest rise in vitamin C levels in the blood. The oral administration of liposomal vitamin C leads to slightly lower blood levels of vitamin C, but even these are still much higher than after the oral administration of non-liposomal vitamin C [7].
IMPROVED UPTAKE
However, even if intact passage through the stomach and intestine is not achieved, liposome products such as liposome vitamin supplements can be of great benefit. Especially lipophilic active substances that have low solubility in water, show poor absorption and thus inferior efficacy. It has been shown that lipid formulations can significantly improve the intestinal uptake of such difficult-to-formulate lipophilic actives [8].
[1] Rein, M.J., Renouf, M., Cruz-Hernandez, C., Actis-Goretta, L., Thakkar, S.K., da Silva Pinto, M. (2013). Bioavailability of bioactive food compounds: a challenging journey to bioefficacy. British Journal of Clinical Pharmacology 75(3), 588-602. doi: 10.1111/j.1365-2125.2012.04425.x.
[2] Fricker, G., Kromp, T., Wendel, A., Blume, A., Zirkel, J., Rebmann, H., Setzer, C., Quinkert R., Martin, F., Muller-Goymann, C. (2010). Phospholipids and lipid-based formulations in oral drug delivery. Pharmaceutical Research 27(8), 1469-1486.
[3] Liposome Technology, Volumes I-III, G. Gregoriadis, Ed. (Informa Healthcare, New York, London, 2007)
[4] Allen, T.M., & Cullis, P.R. (2013). Liposomal drug delivery systems: from concept to clinical applications. Advanced Drug Delivery Reviews 65, 36-48.
[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] Kim H., Kim. Y and Lee J. (2013) Liposomal formulations for enhanced lymphatic drug delivery. Asian Journal of Pharmaceutical Sciences 8, 96-103
[7] Crommelin, D.J.A., Van Hoogevest, P., Storm, G. (2020) The role of liposomes in clinical nanomedicine development. What now? Now what? Journal of Controlled Release 318, 256-263
[8] Metselaar, J.M., Lammers, T. (2020) Challenges in nanomedicine clinical translation. Drug Delivery and Translational Research 10, 721–725