Phytosomes – An Advanced Herbal Technology.

K. Selvaraju*, K.S.G. Arulkumaran, K. Karthick, K. Vengadesh Prabhu, J. Padma Preetha and R. Arrivukkarasu

KMCH College of Pharmacy, Coimbatore-48, Tamil Nadu. India.

ABSTRACT:

The term “Phyto” means plant while “some” means cell-like. Phytosome are little cell like structure. This is an advanced herbal delivery system which contains the bioactive phytoconstituents of herb extract surrounds and bound by Phospholipids. The potential uses of large number of herbal drugs are limited due to their poor absorption and poor bioavailability after oral administration. Phytosomes exhibit better pharmacokinetic and pharmacodynamic profile than conventional herbal extracts. Phytosome technology has been effectively used to enhanced the bioavailability of many popular herbal extracts including milk thistle, ginkgo biloba, grape seed, green tea, hawthorn, ginseng etc, and can be developed for various therapeutic uses or dietary suppliments. The phospholipid molecular structure includes a water soluble head and two fat soluble tails, because of this dual solubility the phospholipid acts as an effective emulsifier which is also one of the chief components of the membranes in our cells.

KEYWORDS: Phytosomes, phospholipids, herbal extracts, bioavailability.

INTRODUCTION:

Phytomedicines are complex chemical mixtures prepared from plants which have been used for health maintenance since ancient times. But many phytomedicines are limited in their effectiveness because they are poorly absorbed when taken by mouth. Most of the biologically active constituents of plants are polar or water soluble molecules. However, water soluble phytoconstituents like flavonoids, tannins, terpenoids etc are poorly absorbed either due to their large molecular size which cannot absorb by passive diffusion or due to their poor lipid solubility, limiting their ability to pass across the lipid rich outer membrane of the enterocytes of the small intestine.¹ Phytosome is a patented technology developed by a leading manufacturer of drugs and nutraceuticals, to incorporate standardized plant extracts or water soluble phytoconstituents into phospholipids to produce lipid compatible molecular complexes, called as phytosomes and so vastly improve their absorption and bioavailability. Phytosomes have improved pharmacokinetic (tissue distribution) and pharmacological parameter which in result can advantageously be used in the treatment of the acute and chronic liver disease of toxic metabolic or infective origin or of degenerative nature. It can also used in anti-inflammatory activity as well as in pharmaceutical and compositions.²

PHYTOSOME TECHNOLOGY:

The flavonoid and terpenoid constituents of plant extracts lend themselves quite well for the direct binding to phosphatidylcholine. Phytosomes results from the reaction of a stoichiometric amount of the phospholipid (Phosphatidylcholine) with the standardized extract or polar solvent.³

Phosphatidylcholine is a bifunctional compound, the phosphatidyl moiety being lipophilic and the choline moiety being hydrophilic in nature. Specifically the choline head of the phosphatidyl choline molecule binds to these compounds while the lipid soluble phosphatidyl portion comprising the body and tail which then envelopes the choline bound material. Hence the phytoconstituents produce a lipid compatible molecular complex with phospholipids, also called as phytophospholipid complex. Molecules are anchored through chemical bonds to the polar choline head of the phospholipids, as can be demonstrated by specific spectroscopic technique.⁴

DIFFERENCE BETWEEN PHYTOSOMES AND LIPOSOMES:

Phytosomes	Liposomes
1. In phytosomes active chemical constituents molecules are anchored through chemical bonds to the polar head of the Phospholipids.	In liposomes, the active principle is dissolved in the medium of the cavity (or) in the layers of the membrane. No chemical bonds are formed.
2. In phytosomes, phosphatidylcholine and the individual plant compound form a 1:1 or 2:1 complex depending on the substance.	In liposomes, hundreds and thousands of phosphatidylcholine molecules surround the water soluble molecule.

This difference results in phytosomes being much better absorbed than liposomes showing better bioavailability. Phytosomes have also been found superior to liposomes in topical and skin care products.⁵

Fig. 1: shows difference between liposome and phytosome

The molecular organization of the liposome (upper segment)

The molecular organization of phytosomes (lower semgnet)

MERITS OF PHYTOSOMES:

Phytosomes have the following merits^6,7

· Marked enhancement of bioavailability.

· Significantly greater clinical benefit.

· Assured delivery to the tissues.

· Added nutritional benefits of phospholipids.

PREPARATION OF PHYTOSOME:

Phytosomes are prepared by reacting from 3-2 moles but preferably with one mole a natural or synthetic phospholipid, such as phosphatidyl choline phosphatidylethanolamine or phosphatidyiserine with one mole of component for example flavolignans either alone or in the natural mixture in aprotic solvent such as –dioxane or acetone from which complex can be isolated by precipitation with non solvent such as aliphatic hydrocarbons or lyophilization or by spray drying. In the complex formation of phytosomes the ratio between these two moieties is in the range from 0.5-2.0 moles. The most preferable ratio of phospholipid to flavonoids is 1:1.⁸

APPLICATIONS OF PHYTOSOMES:

Bombardelli et al reported Silymarin phytosomes in which Silymarin (A standardized mixture of flavanolignans extracted from the fruits of S.marrianum) was complexed with phospholipids. Phytosomes showed much higher specific activity and a longer lasting action than the single components, with respect to percent reduction of odema, antioxidant and free radical scavenging properties.⁹

Tedesco et al reported Silumarin phytosome show better antihepatotoxic activity that Silymarin alone and can provide protection against the toxic effects of aflatoxin B₁ on performance of broiler chicks.¹⁰

Barzaghi et al conducted a human study designed to assess the absorption of Silybin when directly bound to phosphatadylcholine. Plasma silybin levels were determined after administration of single oral doses of silybin phytosome and a similar amount of silybin from milk thistle in healthy volunteers. The results indicated that the absoption of silybin from silybin phytosome is approximately seven times greater compared to the absorption of silybin from regular milk thistle extract (70-80% silymarin content).¹¹

Studies have shown Ginkgo phytosomes (prepared from the standardized extract of Ginkgo biloba leaves) produced better results as vasoactive agent and anti-inflammatory agent to the conventional standardized extracts from the plant.^12,13,14

A study on absorption of phytosomal preparations was performed in healthy human volunteers along with non complexed green tea extract following oral administration. Over the study period of 6 hours the plasma concentration of total flavonoids was more than doubled when coming from the phytosomal versus the nonphytosomal extract. Antioxidant capacity was measured as TRAP (Total Radical – traping Antixodiant Parameter). The peak antioxidant effect was a 20% enhancement and it showed that the phytosome formulation had about double the total antioxidant effect.^15,16

Grape seed phytosome is composed of oligomeric polyphenols (grape proanthocyanidins or procyanidins from grape seed extract, vitis vinifera) of varying molecular size, complexed with phospholipids. The main properties of procyanidin flavonoids of grape seed are an increase in total antioxidant capacity and stimulation of physiological antioxidant defenses of plasma, protection against ischemia / reperfusion induced damages in the heart, protective effects against atherosclerosis thereby offering marked protection for the cardiovascular system.¹⁷

Maiti et al developed the phytosomes of curcumin and naringenin in two different studies. In the first study phytosome of curcumin was developed to oversome the limitation of absorption and to investigate the protective effect of curcumin phospholipid complex on carbon tetrachloride induced acute liver damage in rats. The complex showed enhanced aqueous or n – octanol solubility. The antioxidant activity of the complex was significantly higher than pure curcumin in all dose levels tested. In the other study the developed phytosome of naringenin produced better antioxidant activity than the free compound with a prolonged duration of action, which may be helpful in reducing the fast elimination of the molecule from body^18,19.

EVALUATION OF PHYTOSOMES:

Visualization of phytosomes can be achieved using transmission electron microscopy (TEM) and by Scanning Electron Microscopy (SEM). The Particle size and zeta potential can be determined by dynamic light scattering (DLS) using a computerized inspection system and photon correlation spectroscopy. The entrapment – efficiency of a drug by phytosomes can be measured by the ultracentrifugation techniques.²⁰The surface tension activity of the drug in aqueous solution can be measured by the ring method in a Du Nouy ring tensiometer.²¹

The amount of drug can be quantified by a modified high performance liquid chromategraphic method or by a suitable spectroscopic method. To confirm the formation of a complex or to study the reciprocal interaction between the phytoconstitutents and the phospholipids, ¹H-NMR, ¹³C-NMR, FTIR spectroscopic methods are used. Models of invitro and invivo evaluations are selected on the basis of the expected therapeutic activity of the biological active phytoconstituents present in the phytosomes. For example, invitro antihepatotoxic activity can be assessed by the antioxidant and free radical scavenging activity of the phytosomes.^22,23

CONCLUSION:

Phytosomes are advanced herbal technology shows an improved pharmacokinetic and pharmacological parameter, which can advantageously be used in the treatment of acute liver diseases, cardio protective, anti inflammatory, vasoactive, anticancer, antioxidant, noncancerous prostat enlargement, immune modulator, antiaging and as neutraceuticals. Several excellent phyto constitutents have been successfully delivered in this way exhibiting remarkable therapeutic efficacy in animal as well as in human models. The advantages of phytosomes over conventional and liposomal drug delivery system regarded phytosomes are a value added drug delivery system. As far as the potential of phytosome technology is concerned it has a great future for use in formulation technology and applications of hydrophilic plant compounds.

ACKNOWLEDGEMENT:

We express our sincere thanks to Dr. Nalla G. Palaniswami, Chairman and Dr. Thavamani D. Palaniswami, Managing Trustee of Kovai Medical Center, Research and Educational Trust for giving the facilities and encouragement to carryout this work.

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Received on 28.07.2011

Accepted on 29.08.2011