PHYTOSOMES: A POTENTIAL PHOSPHOLIPID NANOPARTICULATE CARRIER FOR THE BIOAVAILABILITY ENHANCEMENT OF HERBAL EXTRACTS

Headnote

ABSTRACT

Drug bioavailability is a well known issue in the pharmaceutical sector and different strategies have been developed to ameliorate the absorption. In case of poorly absorbed natural derived ingredients, various strategies are being followed in the nutraceutical sector to achieve this goal. The first one is by the chemical derivatization of the chemical product. A second approach involves extensive formulation research of structures called Phytosomes, capable of both stabilizing natural molecules and promoting their intestinal absorption. The Phytosomes approach has the improved pharmacokinetic profile obtained without resorting to pharmacological adjuvant or structural modification of the ingredients. Phytosomes are recent advanced forms of herbal formulations that have enhanced absorption rate, producing better bioavailability than conventional herbal extracts. They can be used in the treatment of the acute and chronic liver disease. Phytosome are created when the standardized extract and active ingredients of an herb are bound to the phospholipids on a molecular level. Phytosome structures contain the active ingredients of the herb surrounded by the phospholipids. Phytosomes are novel formulations which offer improved bioavailability of hydrophilic herbal extract and other similar compounds through the skin or gastrointestinal tract.

Keywords: Phytosomes, Nanoparticles, enhanced bioavailability, Herbal Plant extracts, Phospholipid.

INTRODUCTION

The goal of any drug delivery system is the spatial placement and temporal delivery of the medicaments. Research works are going on to prepare an ideal drug delivery system which satisfies these needs.1 Lipid solubility and molecular size are the major limiting factors for molecules to pass the biological membrane to be absorbed systematically following oral or topical administration. The effectiveness of any herbal product (or medication) is dependent upon delivering an effective level of the active compounds. Phytosomes are recently introduced advanced nanosphere or cell forms of herbal products that are better absorbed, and produce better pharmacokinetic and pharmacodynamic profile than conventional herbal extracts. Phytosomes, term "PHYTO" means plant while "SOME" means cell-like.2 It's a novel emerging technique applied to phytopharmaceutical for the enhancement of bioavailability of herbal extract for medicinal applications. Phytomedicines, complex chemical mixture prepared from plants, have been used in medicine since ancient times and continue to have widespread popular use. The use of Phytosomes is a new advanced modern dosage formulation technology to deliver herbal products and drugs with improved better absorption and, as a result, produce better result than those obtained by conventional herbal extract. Some herbal phytomolecules are poorly miscible with oils and other lipids and often fail to pass through the small intestine because of its lipoidal nature. Plants are endowed with a multitude of medicinal and health giving substances, most of them are secondary metabolite, prominent among these being the flavonoids.3 Multiple approaches for improving bioavailability have been tried. The first one might also seem to the medicinal chemistry approach: by the chemical derivatization of the chemical product, the aim is to obtain compounds showing an improved bioavailability. This approach, however, generates a number of chemical analogues that need to be appropriately screened. An alternative strategy that is also being pursued is the combination of the active molecules with other compounds as adjuvants promoting the active molecule's absorption.

A third approach involves extensive formulation research of structures capable of both stabilizing natural molecules and promoting their intestinal absorption. The formulative research comprises the formation of liposomes, micelles, nanoparticles, nanoemulsions, microsphere or other complexes.3 The Phytosomes approach has the improved pharmacokinetic profile is obtained without resorting to pharmacological adjuvant or structural modification of the ingredients, but by formulating them with a dietary ingredients (soy lecithin). PHYTOSOME is a patented process developed by Indena, a leading supplier of nutraceutical ingredients, to incorporate phospholipids into standardized extract and so vastly improve their absorption and utilization. It's a one kind of Phytosome formulation to deliver the herbal extracts. Certain of the water-soluble phyto-molecules (mainly flavonoids and other polyphenols) can be converted into lipid-friendly complexes, by reacting herbal extract owing to their enhanced capacity to cross the lipid-rich biomembranes and finally, reach the blood. They have improved pharmacokinetic and pharmacological parameters which are advantageous in the treatment of acute disease as well as in pharmaceutical and cosmetic compositions.4 The poor absorption of flavonoid nutrients is likely due to two factors. First, they are multiple ring molecules too large to be absorbed by simple diffusion, while they are not absorbed actively, as occurs with some vitamins and minerals. Second, flavonoid Molecules typically have poor miscibility with oils and other lipids, severely limiting their ability to pass across the lipid-rich outer membranes of the enterocytes of the small intestine. Water-soluble flavonoid molecules can be converted into lipid-compatible molecular complexes, aptly called Phytosomes. Phytosomes are better able to transition from a hydrophilic environment into the lipid-friendly environment of the enterocyte cell membrane and from there into the cell, finally reaching the blood. The lipid-phase substances employed to make flavonoids lipid-compatible are phospholipids from soy, mainly phosphatidylcholine (PC). PC, the principal molecular building block of cell membranes, is miscible both in water and in oil/lipid environments, and is well absorbed when taken by mouth. Precise chemical analysis indicates a Phytosome is usually a hydrophilic herbal extracts linked with at least one PC molecule. A bond is formed between the two molecules, creating a hybrid molecule. This highly lipid-miscible hybrid bond is better suited to merge into the lipid phase of the enterocyte's outer cell membrane.

TYPE OF 'SOMES'

Novel drug delivery system aims to deliver the drug at a rate directed by the needs of the body during the period of treatment, and channel the active entity to the site of action. A number of novel drug delivery systems have emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery. Encapsulation of the drug in vesicular structures is one such system, which can be predicted to prolong the existence of the drug in systemic circulation, and reduce the toxicity, if selective uptake can be achieved. Consequently a number of vesicular drug delivery systems such as liposomes, niosomes, discosomes, and photosomes were developed. Advances have since been made in the area of vesicular drug delivery, leading to the development of systems that allow drug targeting, and the sustained or controlled release of conventional medicines.4

DIFFERENCE BETWEEN PHYTOSOME AND LIPOSOME

Liposomes are microscopic spheres with an aqueous core surrounded by one or more outer shell(s) consisting of lipids arranged in a bilayer configuration. The potential use of liposomes as drug carriers was recognized more than 25 years ago.5 Liposomes are defined as structure consisting of one or more concentric spheres of Lipid bilyares separated by water or aqueous buffer compartments or simply, liposomes are simple microscopic vesicles in which aqeous volume is entirely enclosed by a membrane composed of lipid bilayers. (Figure 1)

Liposomes are now used to deliver certain vaccines, enzymes and drugs to the body. When used in the delivery of certain cancer drugs, liposomes help to shield healthy cells from the drugs toxicity and prevent their concentration in vulnerable tissue (e.g., kidney, liver), lessening or eliminating the common side effects of nausea, fatigue and hair loss.1 Liposomes are especially effective in treating diseases that affect Phytosomes. Also used to carry genes into cells and can be administered by various routes. But there are certain limitations with liposomes.

The fundamental difference between liposomes and Phytosomes is that in liposomes the active principle is dissolved in the medium contained in the cavity or in the layers of the membrane, whereas in the Phytosome it is an integral part of the membrane, being the molecules anchored through chemical bonds to the polar head of the phospholipid (Figure 2).

Liposomes are used primarily in cosmetics to deliver water-soluble substances to the skin. A liposome is formed by mixing a water-soluble substance with phosphatidylcholine. No chemical bond is formed; the phosphatidylcholine molecules surround the water-soluble substance. There may be hundreds or even thousands of phosphatidyl-choline molecules surrounding the water-soluble compound. In contrast, with the Phytosome process the phosphatidyl-choline and the individual plant components actually from a 1:1 or a 2:1 complex depending on the substance. This difference results in Phytosomes being much better absorbed that liposomes. Phytosomes are superior to liposomes in skin care products.3,7 (Figure 3)

PHOSPHOLIPIDS

Phospholipids (pronounced fos-fo-lip-ids) are complex substance with chemical, biochemical and nutritional characteristics that place them in a unique nutritional category. They are complex lipid molecules indispensable for life and are abundant in all human and the other known forms to make cell membranes. The profound biochemical importance of phospholipids is reflected in their extraordinary clinical benefits as dietary supplements. The phospholipids are readily compatible with the entire range of vitamins, minerals, metabolites, and herbal preparations currently consumed as the dietary phospholipids and omega-3 fatty acid works in functional synergy in cell membranes. Phosphatidylcholine is a bifunctional compound miscible both in water and in oil environments, and is well absorbed when taken by mouth.3 Phosphatidyl-choline is not merely a passive "carrier" for the bioactive compounds, but is itself a bioactive nutrient with documented clinical efficacy for liver disease, including alcoholic hepatitis. Phosphatidylcholine is present in egg yolk, brain tissue and a wide variety of animal fat and plant oils. It is routinely present in the bile fluid, to help emulsify food ingredient for absorption.

A number of drug delivery system are based entirely on Phosphatidylcholine such as liposomes, ethosomes, phytosomes, transferosomes, and nanocochhelates. The hydrophilic and hydrophobic domain/ segment within the molecular geometry of amphiphilic lipids orient and self organize in ordered supramolecular structure when confronted with solvents. Some commonly used synthetic phospholipids are dioleoyl-phosphatidyl-choline (DOPC), dioleoyl-phosphatidyl-ethanolamine (DOPE), distearoylphosphatidyl-choline (DSPC), distearoyl-phosphatidylethanolamine (DSPE)3

ADVANTAGES OF PHOSPHOLIPIDS BASED CARRIER SYSTEM IN COMPARISON TO OTHER DELIVERY SYSTEMS9

. These systems show enhanced permeation of drug through skin for transdermal and dermal delivery.

. These are platform for the delivery of large and diverse group of drugs (peptides, protein molecules).

. Their composition is safe and the components are approved for pharmaceutical and cosmetic use.

. Low risk profile-the toxicological profiles of the phospholipids are well documented in the scientific literature.

. High market attractiveness for products with proprietary technology. Relatively simple to manufacture with no complicated technical investments required for production of Ethosomes.

. The vesicular system is passive, non-invasive and is available for immediate commercialization.

MERITS OF PHYTOSOMES OVER

CONVENTIONAL DOSAGE FORMS10-13

. There is a dramatic enhancement of the bioavailability of botanical extracts due to their complexation with phospholipids and improved absorption in the intestinal tract.

. They permeate the non-lipophillic botanical extract to allow better absorption from the intestinal lumen, which is otherwise not possible.

. The formulation of Phytosomes is safe and the components have all been approved for pharmaceutical and cosmetic use.

. They have been used to deliver liver protecting flavonoids because they can be made easily bioavailable by phytosomes.6

. In addition to this, phosphatidylcholine is also hepatoprotective and so provides a synergistic effect for liver protection.

. This technology offers cost effective delivery of phytoconstituents and synergistic benefits when used as functional cosmetics to protect the skin against exogenous or endogenous hazards in normal as well as stressful environmental conditions

. They can be also used for enhanced permeation of drug through skin for transdermal and dermal delivery.

. They can be widely used in cosmetics due to their improved skin penetration and have a high lipid profile. Phytosomal formulations can be used as functional cosmetics.1

. Phosphatidylcholine, an essential part of the cell membrane used in phytosome technology, acts as a carrier and also nourishes the skin. There is no problem with drug entrapment during formulation preparation. Also, the entrapment efficiency is high and more over-predetermined; because the drug itself forms vesicles after conjugation with lipid. They offer a better stability profile because chemical bonds are formed between the phosphatidylcholine molecules and phytoconstituents. The phytosomal system is passive, non-invasive and can is suitable for immediate commercialization. The dose requirement is reduced due to improved absorption of the main constituent. They can also be given in smaller quantities to achieve the desired results.9

. Low risk profile: This technology has no large-scale drug development risk since the toxicological profiles of the phytosomal components are well documented in the scientific literature. Highly attractive market profile for products with proprietary technology. Relatively simple to manufacture with no complicated technical investment required for the production of Phytosomes. They also have many applications in the pharmaceutical, veterinary, and cosmetic fields.

PREPARATION OF PHYTOSOME

Phytosomes are novel complexes which are prepared by reacting from 2-3 moles but preferably with one mole of a natural or synthetic phospholipid, such as Phosphatidylcholine, phosphatidylethanolamine or phosphatidylserine with one mole of component for example-flavolignanans, 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 phospholipids to flavonoids is 1:17. In the Phytosome preparations (Figure 6), phospholipids are selected from the group consisting of soy lecithin, from bovine or swine brain or dermis, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine in which acyl group may be same or different and mostly derived from palmitic, stearic, oleic and linoleic acid.

Selection of flavonoids are done from the group consisting of quercetin, kaempferol, quercretin-3, rhamnoglucoside, quercetin-3-rhamnoside, hyperoside, vitexine, diosmine, 3-rhamnoside, (+)catechin, (-) epicatechin, apigenin-7-glucoside, luteolin, luteolinglucoside, ginkgonetine, isoginkgonetine and bilobetine. Some liposomal drugs complex operate in the presence of the water or buffer solution where as phytosomes operate with the solvent having a reduced dielectric constant. Starting material of component are insoluble in chloroform, ethyl ether or benzene. They become extremely soluble in these solvents after forming phytosomes. This chemical and physical property change is due to the formation of a true stable complex.2,5

CHARACTERIZATION AND EVALUATION OF PHYTOSOME

The behavior of phytosomes in both physical and biological systems is governed by factors such as the physical size, membrane permeability, percentage of entrapped solutes, and chemical composition as well as the quantity and purity of the starting material. Phytosomes can be characterized in terms of their physical attributes i.e. shape, size, distribution, percentage drug captured, entrapped volume, percentage drug released and chemical composition.

Visualization

Visualization of phytosomes can be achieved using Transmission Electron Microscopy (TEM) and by Scanning Electron Microscopy (SEM) electron microscopic techniques used to assess liposome shape and size are mainly negative-stain transmission microscopy and scanning electron microscopy (Figure 7). The later technique requires dehydration of the sample prior to examination and is less preferred. Negative stain electron microscopy visualizes relatively electron transparent liposomes or phytosomes as bright area against a dark background (hence termed as negative stain).

Spectroscopic Evaluations

To confirm the formation of a complex or to study the reciprocal interaction between the phytoconstituent and the phospholipids, the following spectroscopic methods are used;

FTIR: The formation of the complex can be also be confirmed by IR spectroscopy by comparing the spectrum of the complex with the spectrum of the individual components and their mechanical mixtures. FTIR spectroscopy is also a useful tool for the control of the stability of phytosomes when micro-dispersed in water or when incorporated in very simple cosmetic gels. From a practical point of view, the stability can be confirmed by comparing the spectrum of the complex in the solid form (phytosomes) with the spectrum of its micro-dispersion in water after lyophilization, at different times. In the case of simple formulations, it is necessary to subtract the spectrum of the excipients (blank) from the spectrum of the cosmetic form at different times, comparing the remaining spectrum of the complex itself.

1H-NMR: The NMR spectra of (+)-catechin and its stiochiometric complex with distearoyl phosphatidylcholine have been studied by Bombardelli et al. in polar solvents, there is a marked change of the 1H-NMR signal originating from the atoms involved in the formation of the complex, without any summation of the signal peculiar to the individual molecules. The signals from the protons belonging to the flavonoid are to be broadened that the proton cannot be relieved. In the phospholipids, there is broadening of all the signals while the singlet corresponding to the N-(CH3)3 of choline undergo an upliftshift. Heating the sample to 60°C results in the appearance of some new broad bands, which correspond mainly to the resonance of the flavonoid moiety.4

13C-NMR: In the 13C-NMR spectrum of (+)-catechin and its stoichiometric complex with distearoyl phosphatidylcholine, particularly when recorded in C6D6 at room temperature, all the flavonoid carbons are clearly invisible. The signals corresponding to the glycerol and choline portion of the lipid (between 60-80ppm) are broadened and some are shifted, while most of the resonance of the fatty acid chain retains their original sharp line shape. After heating to 60°C, all the signal belonging to the flavonoid moieties reappear, although they are still very broad and partially overlapping.4

PHARMACEUTICAL SCOPE OF PHYTOSOME

. It enhances the absorption of lipid insoluble polar phytoconstituents through oral as well as topical route showing better bioavailability, hence significantly greater therapeutic benefit.

. Appreciable drug entrapment.

. As the absorption of active constituent(s) is improved, its dose requirement is also reduced.

. Phosphatidylcholine used in preparation of Phytosomes, besides acting as a carrier also acts as a hepatoprotective, hence giving the synergistic effect when hepatoprotective substances are employed.

. Chemical bonds are formed between phosphatidylcholine molecule and phytoconstituent, so the Phytosomes show better stability profile.

. Application of phytoconstituents in form of phytosome improves their percutaneous absorption and act as functional cosmetics.

Phytosome® complexes can be formulated both orally and topically. In order to obtain the best performances of this technogical innovation both in terms of formulating manageability and enhanced bioavailability (as appropriate disintegration and dissolution time of oral forms, for instance) Indena suggests the most appropriate manufacturing procedures to obtain effective formulations.

Softgelatin capsules

Softgelatin capsules represent an ideal solution to formulate Phytosome® complexes. The Phytosome® complex can be dispersed in oily vehicles to obtain suspensions to be filled in softgelatin capsules. Vegetable or semi-synthetic oils can be used to this purpose. We recommend a granulometry of 100% <200 µm to best perform capsule production. According to Indena experience, not all the Phytosome® complexes behave in the same way when dispersed in oily vehicles and when the oily suspension is filled in the softgelatin capsules; for this reasons preliminary feasibility trials should be performed to select the most suitable vehicle.

Hard gelatin capsules

The Phytosome® complex can be formulated in hard gelatin capsules as well. A direct volumetric filling process (without precompression) can be applied, even if the apparently low density of the Phytosome® complex seems to limit the maximum amount of powder that can be filled into a capsule (usually not more than 300 mg for a size 0 capsule). With a piston tamp capsule filling process, however, it is possible to increase the amount of powder which can be filled in a capsule, but precompression might affect the disintegration time. They recommend to carefully monitoring the related parameters during product/process development. A preliminary dry granulation process is advisable define the best manufacturing process. One example,

Hard gelatine capsule formulation with Phytosome® complex

Ginkgoselect® Phytosome® 180.0 mg

Dicalcium phosphate dihydrate 196.0 mg

Silicified microcrystalline cellulose 47.0 mg

Croscarmellose sodium 23.0 mg

Talc 2.0 mg

Magnesium stearate 2.0 mg

Tablets

Dry granulation represents the ideal manufacturing process to obtain tablets with higher unitary doses and with suitable technological and biopharmaceutical properties. However, due to the limited flowability, potential stickiness and low apparent density of the Phytosome® complex, a direct compression process can be applied only for low unitary doses; note that whenever a direct compression process is applied, the Phytosome® complex should be diluted with 60-70% of excipients to optimize its technological properties and to obtain tablets with appropriate technological and biopharmaceutical characteristics.

On the other hand, wet granulation should be avoided due to the negative effect of water and heat (granulation/drying) on the stability of the phospholipid complex. One example,

Tablet formulation with Phytosome® complex

Leucoselect® Phytosome® 100.0 mg

Soy polysaccharides 138.0 mg

Corn starch 100.0 mg

Silicon dioxide 6.0 mg

Talc 3.0 mg

Magnesium stearate 3.0 mg

Topical dosage forms

The Phytosome® complex can be formulated topically as well. The ideal process to incorporate the Phytosome® complex in emulsion is to disperse the phospholipidic complex in a small amount of the lipidic phase and add it to the already created emulsion at low temperatures (not higher than 40°C). The Phytosome® complexes are dispersible in the main lipidic solvents employed in topical formulations.

In case of formulations containing a limited amount of lipids, the Phytosome® complex might also by dispersed into the watery phase, and again added to the final formulation at temperature lower than 40°C.

SILYBIN PHYTOSOME FOR LIVER SUPPORT-AN UPDATE

Silymarin (Figure 8) and its predominant active constituent silybin are proven antioxidants and liver protectants. In experimental settings silymarin scavenges oxygen-and nitrogen-centered free radicals, inhibits lipid peroxidation, and prevents injury to DNA from toxins or radiation.8 Although in animal experiments and some human studies, milk thistle constituents have conserved liver glutathione, inhibited liver fibrogenesis, and supported liver regeneration, clinical trials have been inconsistent. In trials of viral hepatitis, alcoholic liver damage or other liver diseases, silymarin and silybin improved enzyme damage indicators and (at times) improved antioxidant status but did not consistently improve symptoms.8,14,15

ANTI-INFLAMMATORY AND ANTICANCER POTENTIAL OF SILIPHOS

Mechanistically, the anti-inflammatory and anticancer effects of silybin and the other flavonolignans are related to the potent inhibition of nuclear factorkappaB (NF-kB). This transcription factor is linked with numerous genes that regulate inflammation, immune function, stress response, cell differentiation, apoptosis and cell survival, and is critically involved in the processes of development and progression of cancers. Silybin is a potent inhibitor of NF-kB activation, as induced by a variety of anti-inflammatory agents. Manna et al tested silybin in a number of in vitro human cell experimental systems and found it regulated NF-kB 100 times better than aspirin. Furthermore, NF-kB is itself regulated by several kinase enzymes that belong to the mitogen-activated protein kinase (MAPK) family and by the C-Jun N-terminal kinase (JNK). The Manna study found silybin also blocked these kinases without posing a threat to cell survival. Currently (mid-2009), at least 11 clinical trials are in progress that is utilizing silybin, silymarin, or Siliphos for liver protection and other therapeutic applications. There is other substantial laboratory evidence that the milk thistle flavonolignans have anticancer potential. Scientists reviewed the considerable in-vitro and in-vivo evidence that silybin alone or as a Phytosome has anti-proliferative, anti-angiogenic, and anti-metastatic effects. Well tolerated even at very high doses silybin and/or silibin-PC complex are worthy of further exploration as cancer therapeutics. A phase II randomized trial is underway in children and young adults with acute lymphoblastic leukemia. This trial is designed to assess silymarin for its liver-protective effects against chemotherapy-induced toxicity.

PHARMACOKINETICS OF SILYBIN-PHOSPHATIDYLCHOLINE COMPLEX

In 1990, Malandrino et al succeeded in improving the bioavailability of silymarin extract by complexing it with soy PC-a phytosome. Subsequently,a more purified silybin was complexed with PC. The intermolecular bonding of silybin with PC proved to be specific and stable, and the resulting molecular complex is more soluble in lipophilic, organic solvents. This property predicts the enhanced ability of phytosomes to cross cell membranes and enter cells.16

Animal Studies

The superior bioavailability of silybin complexed with PC over non-complexed silybin has been documented through pharmacokinetic studies conducted in rats and humans. Figure 9 illustrates that, in rats, a large dose of silybin given orally as plain silymarin remained virtually undetectable in the plasma for the six-hour experiment. In marked contrast, when the same amount of silybin (200 mg per kg body weight) was given as Siliphos®, a silybin-PC phytosome, it was detected in the plasma within minutes, and by one hour its levels had peaked. Its plasma levels remained elevated past the six-hour mark. The superior absorption of the silybin from Siliphos is reflected in its clearance in the urine. Figure 9 illustrates the silybin from Siliphos remained elevated at 70 hours following oral dosing, while the silybin given alone barely rose above detectable levels until after 25 hours. Siliphos has been demonstrated to reach the liver, its target organ. Silybin was substantially present in bile fluid two hours following the administration of Siliphos and the liver continued to secrete silybin into the bile during the entire study. Silybin, given as the non-complexed silymarin, was barely detectable in the bile during the same period.15

Mukerjee & co-associates (2008)4: Hesperetin is a potent phytomolecule abundant in citrus fruits, such as grapefruit and oranges. In spite of several therapeutic benefits viz. antioxidant, lipid-lowering, anti-carcinogenic activities their shorter half life and lower clearance from the body restricts its use. To overcome this limitation, recently Mukerjee et al. developed a novel hesperetin phytosome by complexing hesperitin with hydrogenated phosphatidylcholine. This complex was then evaluated for antioxidant activity in CCl4 intoxicated rats along with pharmacokinetic study revealed that the phytosome had higher relative bioavailability than that of parent molecule at the same dose level.

Maiti & co-associates (2005)4: developed the quercetin phospholipids phytosomal complex by a simple and reproducible method and also showed that the formulation exerted better therapeutic efficacy than the molecules in rat liver injury induced by carbon tetrachloride.

CONCLUSION

Considering the advantages of this drug delivery system-Phyrosomes and also its modifications or upgraded versions like Enzymosomes, Hemosomes, Virosomes, Erythrosomes, etc have emerged as a dynamic mode for Targeted Drug Delivery. Phytosomes are novel formulations which offer improved bioavailability of hydrophilic flavonoids and other similar compounds through the skin or gastrointestinal tract. They have many distinctive advantages over other conventional formulations. 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. Standardized plant extracts or mainly polar phytoconstituents like flavonoids, terpenoids, tannins, xanthones when complexed with phospholipids like Phosphatidylcholine give rise to a new drug delivery technology called phytosome showing much better absorption profile following oral administration owing to improved lipid solubility which enables them to cross the biological membrane, resulting enhanced bioavailability i.e. more amount of active principle in the systemic circulation. Phytosomes have improved pharmacokinetic and pharmacological parameter, which in result can advantageously be used in treatment of acute liver diseases, either metabolic or infective origin. Absorption of phytosome in gastro-intestinal tract is appreciably greater resulting in increased plasma level than the individual component. This means more amount of active constituent becomes present at the site of action (liver, brain, heart, kidney etc) at similar or less dose as compared to the conventional plant extract. Phytosomes can be developed for different therapeutic purposes like hepatoprotective, cardiovascular, liver diseases, antiinflammatory, immunomodulator, anticancer, antidiabetic etc or for prophylactic and health purposes as nutraceuticals, in due course.

References

REFERENCES

1. Formulation of Phytosomes in www.phytosomes.info. URL: http:// www.phytosomes.info/ public/ formulating_phytosome.asp. Accessed on 2 June 2012.

2. Jain N, Gupta B P, Thakur N; Phytosome: A novel drug delivery system for herbal medicine. International journal of Pharmaceutical Science and Drug Research. 2010; 2(4):224-228.

3. Awasthi R, Kulkarni G, Pawar V; Phytosome: An approach to increase the bioavailability of plane extracts. International journal of Pharmacy and Pharmaceutical Science. 2011; 3(2):1-3.

4. Rathore P, Swami G; Planterosome: A potential phyto-phospholipid carrier foe the bioavailability enhancement of herbal extracts. International Journal of Pharmaceutical Science and Research. 2012; 3(3):737-755.

5. Arcadio Chonn and Pieter R. Cullis; Recent advances in liposomal drug delivery system. Current opinion in Biotechnology. 1995; 6:698-708.

6. Pandey S, Patel K; Phytosomes: Technical Revolution in Phytomedicine. International journal of PharmaTech Research. 2010; 2(1):627-631.

7. Bombardelli E, Spelta M; Phospholipid-polyphenolcomplexes: a new concept in skin care ingredients. Cosm & Toil. 1991; 106:69-76.

8. Parris M Kidd; Bioavailability and Activity of Phytosome Complexes from Botanical Polyphenols: The Silymarin, Curcumin, Green Tea, and Grape Seed Extracts. Altern Med Rev. 2005; 14(3):226-246.

9. Sindhumol P G, Thomas M, Mohanachandran P S; Phytosomes: A Novel dosage form foe enhancement of bioavailability of botanicals and nutraceuticals", International Journal of Pharmacy and Pharmaceutical science. 2010; 2(4):10-14.

10. Kidd P, Head K; A review of the bioavailability and clinical efficacy of milk thistle Phytosome: a silybinphos phatidylcholine complex. Altern Med Rev. 2005; 10(3):193-203.

11. Bombardelli E; Phytosomes in functional cosmetics. Fitoterapia. 1996; 65(5):320-327.

12. Bombardelli E, Spelta M, Loggia Della R, Sosa S, Tubaro A; Aging Skin: Protective effect of silymarin-PHYTOSOME. Fitoterapia. 1992; 62(2):115-122.

13. Gupta M, Ashawal S, Saraf S; Phytosomes: a novel approach towards functional cosmetics. J Plant Science. 2007; 4(1):644-649.

14. Kidd P, Head K; A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybinphosphatidylcholine complex (Siliphos®). Altern Med Rev. 2005; 10(1):193-203.

15. Mayer K E, Myers R P, Lee S S; Silymarin treatment of viral hepatitis: a systematic review.J Viral Hepatitis. 2005; 12(1):559-567.

16. Pradhan S C, Girish C; Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J Med Res. 2006; 124(1):491-504.

17. Phytosomes® in www.indena.com. URL: http://www.indena.com/index.php/phytosome.html. Accessed on 12 June 2012.