Welcome to www.phytosomes.info

The Phytosome^® formulation increases the absorption of active ingredients when topically applied on the skin^(1-10), and improves systemic bioavailability when administered orally^(11-15). In water medium, a Phytosome^® will assume a micellar shape, forming a liposome-like structure.

Bioavailability of flavonoids, both in aglyconic or glycosidic form, is reported to be low and erratic due to limited absorption, elevated presistemic metabolism and rapid elimination. Flavonoid aglycons and glycosides, once ingested, reach the small intestine intact and then are metabolized to the methylated, glucuronidated or sulfated metabolites. Flavonoids or flavonoids metabolites that reach the colon are usually further metabolized by local enzymes and then absorbed. This figure is at the base of a non-linear pharmacokinetics and has to be taken into account when evaluating the relationship among in vitro biochemical effects, oral dosages and plasma levels.

Here below we are reporting some examples of increased bioavailability with different phytochemicals and different administration routes.

The pharmacokinetic profile of Ginkgoselect® Phytosome® has been defined in experimental animals(16) and in human volunteers(17). Its bioavailability has been compared to Ginkgo biloba extract (GBE). Chart 1 reports human plasma concentrations of ginkgolide A which, according to AUC, shows a 3.5 folds higher absorption of the Ginkgoselect® Phytosome®. Fifteen healthy volunteers were randomly divided into two groups and administered respectively 160 mg of free formulation of GBE (corresponding to 9.6 mg of terpene lactone) and 160 mg of Ginkgoselect® Phytosome® (corresponding to the same amount of terpene lactone). The subjects switched formulations after a week of wash out. Blood samples were collected at 30, 60, 120, 180, 240, 300 and 400 min after ingestion. Terpene lactone detection was performed by means of liquid cromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-ITMS). Ginkgolides A, B and bilobalide were absorbed to a higher extent (about threefold) after administration of Ginkgoselect® Phytosome®.	Chart 1. Increase in plasma levels of total ginkgolides (A and B) and bilobalide in healthy volunteers5
GBE and Ginkgoselect® Phytosome® demonstrated their effective antioxidant capacity by increasing total plasma and brain antioxidant capacity in vivo, according to the experimental protocol described below, as well. Ginkgoselect® Phytosome®, though, induced a higher antioxidant protection compared to GBE. GBE and Ginkgoselect® Phytosome® have been administered to a group of 5 rats respectively (plus a control group) at 300 mg/kg/day (and 300 mg/kg/day as GBE for the complexed form). The total plasma antioxidant capacity and the brain antioxidant capacity have been measured by FRAP method. Ginkgoselect® Phytosome® total plasma antioxidant capacity in rats resulted 27.9% higher compared to GBE (Chart 2).	Chart 2. Total plaama antioxidant capacity in rats (FRAP: ferric reducing ability of plasma)
Similar results have been also seen comparing the absorbtion (-)-epigallocatechin 3-O-gallate (EGCG), the main constituent of  Greenselect® Phytosome®(18). Twelve healthy male volunteers were randomly divided in two groups. One received a single dose of Greenselect® (containing 240 mg of tea catechins by HPLC). The second group received 1,200 mg of Greenselect® Phytosome® (containing 240 mg of tea catechins by HPLC). EGCG was chosen as the biomarker for absorption.The peak concentration at 2 hours is more than doubled with Greenselect® Phytosome® in comparison with to the non complexed Greenselect®. Further the plasma levels of EGCG remain considerably higher with Greenselect® Phytosome® (Chart 3).	Chart 3. Time course of EGCG after ingestion of Greenselect® and Greenselect® Phytosome®
As demonstrated by pharmacokinetic studies in comparison with free silybin and silymarin, Siliphos® represents the most absorbable form of silybin known until now. In rats, after oral administration of 200 mg/kg of silybin, the plasma levels of this drug and its conjugated metabolites were below the analytical detection limit, while, after oral administration of Siliphos® (200 mg/kg as silybin) the plasma levels of silybin (free and total) were easily measurable (Chart 4.). Furthermore, after oral administration of Siliphos®, the biliary elimination of silybin was not complete at 24 h and accounted for about 3.7% of the administered dose. The compound was rapidly excreted in urine where at 72 h the amount recovered accounted for about 3.3%. After administration of uncomplexed silybin, biliary and urinary elimination accounted for only 0.001% and 0.032%, respectively(12).	Chart 4. Mean plasma levels of total silybin after treatment with Siliphos® and after silybin in rats (n=6)
Finally as an example, an activity comparison between the Phytosome® and non Phytosome® form by topical application is here reported as well. The anti-inflammatory and anti-oedemigenous effects of the 18ß-Glycyrrhetinic Acid Phytosome® were assessed in the experimental model of Croton oil-induced oedema reduction. At the same dose (0.16 μM), the action of the 18ß-Glycyrrhetinic Acid Phytosome® was found to be greater and to last longer than that of 18ß-glycyrrhetic acid alone. This means that the complex with the Phytosome® not only increases the active ingredient tolerability and absorption, but also improves its efficacy.	Chart 5. Comparison action on oedema reduction between the free and complexed 18ß-Glycyrrhetic Acid in a croton oil model.

 

1. Bombardelli E, Curri SB, Gariboldi P. Gariboldi, cosmetic utilization of complexes of Panax ginseng saponins with phospholipids in PHYTOSOME® form. Fitoterapia 1989;60:55–70 [Suppl. to issue N.1]. 
2. Bombardelli E. Phytosome®: new cosmetic delivery system. Boll Chim Farma 1991;130:431–8. 
3. Bombardelli E (Indena S.p.A.). Pharmaceutical and cosmetic compositions containing complexes of flavanolignans with phospholipids. Patent EP0300282B1, 1992. 
4. Bombardelli E, Patri G, Pozzi R (Indena S.p.A.). Complexes of saponins and their aglycons with phospholipids and pharmaceutical and cosmetic compositions containing them. Patent US5166139, 1992. 
5. Bombardelli E, Patri G (Indena S.p.A.). Complex compounds of bioflavonoids with phospholipids, their preparation and use, and pharmaceutical and cosmetic compositions containing them. Patent EP0275005B1, 1993. 
6. Bombardelli E, Patri G, Pozzi R (Indena S.p.A.). Complexes of saponins with phospholipids and pharmaceutical and cosmetic compositions containing them. Patent EP0283713B1, 1993. 
7. Bombardelli E, Sabadie M (Indena S.p.A.–Sanofi S.A.). Phospholipidic complexes of Vitis vinifera extracts, process for their preparation and pharmaceutical and cosmetic compositions containing them. Patent EP0300282B1, 1993. 
8. Di Pierro F (Indena S.p.A.). Pharmaceutical and cosmetic compositions against skin aging. Patent EP0283713B1, 1993.
9. Bombardelli E, Cristoni A, Morazzoni P. Phytosome®s in functional cosmetics. Fitoterapia 1994;65:387–401.
10. Bombardelli E, Patri G, Pozzi R (Indena S.p.A.). Complexes of neolignan derivatives with phospholipids the use thereof and pharmaceutical and cosmetic formulations containing them. Patent EP0464297B1, 1995. 
11. Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E. Pharmacokinetic studies on IdB 1016, a silybin-phosphatidylcholine complex, in healthy human subjects. Eur J Drug Metab Pharmacokinet 1990;15:333–8. 
12. Morazzoni P, Magistretti MJ, Giachetti C, Zanolo G. Comparative bioavailability of silipide, a new flavolignan complex, in rats. Eur J Drug Metab Pharmacokinet 1992;17:39–44. 
13. Morazzoni P, Montalbetti A, Malandrino S, Pifferi G. Comparative pharmacokinetics of silipide and silymarin in rats. Eur J Drug Metab Pharmacokinet 1993;18:289–97.
14. Maiti K, Mukherjee K, Gantait A, Ahamed HN, Saha BP, Mukherjee PK. Enhanced therapeutic benefit of quercetin–phospholipid complex in carbon tetrachloride-induced acute liver injury in rats: a comparative study. Iran J Pharmacol Ther 2005;4:84–90. 
15. Marczylo TH, Verschoyle RD, Cooke DN, Morazzoni P, Steward WP, Gescher AJ. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother Pharmacol 2007;60:171–7.
16. Carini M., Aldini G., Rossoni G., Morazzoni P., Maffei Facino R.; Complexation of Ginkgo biloba extract with phosphatidylcholine improves cardioprotective activity and increase the plasma antioxidant capacity in the rat.; Planta Med.; 67; 2001; 326-330.
17. Mauri P., Simonetti P., Gardana C., Minoggio M., Morazzoni P., Bombardelli E., Pietta P., Liquid chromatography/atmospheric pressure chemical ionization mass spectrometry of terpene lactones in plasma of volunteers dosed with Ginkgo biloba L. extracts, Rapid Commun Mass Spectrom. 2001;15(12):929-34.
18. Pietta P., Simonetti P., Gardana C., Brusamolino A., Morazzoni P., Bombardelli E., Relationship between rate and extent of catechin absorption and plasma antioxidant status, Biochem Mol Biol Int. 1998 Dec;46(5):895-903.