Phytosomes–A Novel Approach in Herbal Drug Delivery System

 

Ms. Yogita Rayate*, Ms. Shital Shewale, Ms. Aishwarya Patil, Dr. Manojkumar Nitalikar, Dr. Shrinivas Mohite

Rajarambapu College of Pharmacy, Kasegaon.

 

ABSTRACT:

Phytosome is novel drug delivery system which is a patented technology that combines hydrophilic bioactive phytoconstituents of herbal extract and bound by phospholipids.Phytosomes are more bioavailable than conventional herbal extract due to its enhanced capacity to cross the lipid-rich biomembranes and reach circulation.Applied to standardized plant extracts,water soluble phytoconstituents and many popular extracts including curcumin ,grape seeds, gingko biloba,arjuna bark and panax ginseng etc.Phytosomes absorption in GIT is greater which results in increased plasma level than individual components.The current review highlights an importants of phytosomes and their therapeutic application against various human problems and diseases.

 

 

 

INTRODUCTION:

Phyto-chemical science and phyto-pharmacological science established numerous plant compounds with various biological activities and health promoting benefits such as anti-oxidative,anti-inflammatory, anti-cancer and for age-related diseases namely memory loss, osteoporosis, diabetic wounds, immune and liver disorders, etc.[3]

 

 

Most of these biologically active constituents of plants show poor bioavailability owing to their large molecular size, comprising of multiple rings, which cannot be absorbed by passive diffusion, or due to their poor lipid solubility; severely limiting the ability to pass across the lipid‐rich biological membranes. Phytoconstituents, despite having excellent bioactivity in vitro, demonstrate less or no in vivo actions due to their poor lipid solubility or improper molecular size or both, resulting in poor absorption and poor bioavailability [13]. Lipid solubility and molecular size are the major limiting factors for molecules to pass the biological membrane and to be absorbed systematically following oral or topical administration. Some phytoconstituents are destroyed in the gastric environment when taken orally.

 

The term "phyto" means plant, while "some" means cell-like. Therefore, phytosomes is a "phytophospholipid complex" resembling a small cell. Phytosomes are produced by a patented process whereby standardized plant extracts or their constituents are bound to phospholipids, mainly phosphatidylcholine, producing a lipidcompatible molecular complex [4].

 

Phytosomes exhibit a better pharmacokinetic and pharmacodynamics profile than conventional herbal extracts. The phytosomes technology markedly enhances the bioavailability of phytomedicine and has effectively enhanced the bioavailability of many popular herbal extracts, including Milk thistle, Ginkgo biloba, Grape seed, Hawthorn, Ginseng. 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. [4] When different phytoconstituents such as flavonoids, terpenes and saponins form reversible complexes with phospholipids, they showed that their anti-inflammatory and long lasting than those observed after administration of same amount of substance in free form. This is mainly due to the complexation of active ingredients with phospholipids [5].

 

ADVANTAGES OF PHYTOSOMES:

Phytosomes shows following advantages:

·        Enhancement of drug bioavaibility occurs.

·        It increases the absorption of lipid insoluble hydrophilic polar phytoconstituents through oral also topical route and increasing the bioavailability.[7]

·        Phytosomes are required in small dose and also maximum absorption occurs.

·        Phytosomes having better drug entrapment efficiency.

·        Due to formation of chemical bonds, phytosomes show better stability profile. PC used in the preparation of phytosomes, besides acting as a carrier also acts as a hepatoprotective, gives the synergistic effect.[2]

·        Phytosomes are widely used in cosmetics due to improved skin penetration and high lipid profile

·        Various phytoconstituents of herbal extracts are protected from destruction by digestive secretions and gut bacteria.[12]

·        They have been utilized to convey liver protecting flavonoids, as they are made of phytosomes

·        Which have high bioavailability. Apart from this, Phosphatidylcholine is hepatoprotective in

·        nature.[6]

·        They can be also utilized to improve the diffusion of drug through the skin in transdermal and

·        Dermal drug delivery.

 

PROPERTIES OF PHYTOSOMES-

1.      Phytosomes are prepared by reaction of phospholipid with phytoconstituents of plant extract.

The spectroscopic data reveals that the phopspholipid- substrate interaction is due to the formation of hydrogen bond between the polar head (i.e., phosphate and ammonium group) and the polar functionalities of the phytoconstituents [4].

 

2.      When phytosmes treated with water then they show micellar shape resembling liposomes.

 

3.      Phytosomes are lipid–compatible complexes having phytoconstituents and phospholipid in a stoichiometric ratio generally in 1:1 or 2:1.

 

4.      Phytosomes are lipophilic substances with a definite melting point ,freely soluble in non-polar solvent and moderately soluble in fats .[2]

 

5.      Phytosomes show more bioavailability as compared to conventional herbal extract which has been demonstrated by pharmacokinetic studies or by pharmacodynamic tests in experimental animals.

 

DIFFERENCE BETWEEN PHYTOSOME AND LIPOSOME-

 

Fig.1.

 

·        In liposomes ,the active principle is dissolved in the medium of the cavity or in the membrane but in phytosomes active chemical constituents molecules are anchored through chemical bonds to the polar head of the phospholipids.[shown in Fig.1]

·        In phytosomes ,PC and the individual plant compound form 1:1 or 2:1 complex depending on the substance,but in liposomes phosphatidyl choline molecules surround the water soluble molecule.[9]

·        Phytosomes are prepared in solvent having low dielectric constant and liposomes are prepared in solvent having high dielectric constant.

·        Phytosomes having more physical stability due to formation of chemical bonds as compared to liposomes .[1]

·        Phytosomes are more superior to lipoomes in cosmetic products.

 

METHOD OF PREPARATION-

Phytosomes are prepared by reacting natural or synthetic phospholipids with active components like bioflavonoid, flavolignan and polyphenolic constituents.

 

Solvent evaporation method is the most common technique used for the preparation of phytosomes [11] (shown in Fig.2).

 

 

Fig.2-Common stages of preparation of phytosome

 

EVALUATION OF PHYTOSOMES-

1.      Particle size-[11]

Vesicle size and zeta potential of phytosomes can be determined by dynamic light scattering which uses a computerized inspection system.

2.      % Yield determination-[8]

It can be calculated by using following formula,

%Yield=(practical yield /Theoretical yield)*100

3.      Visualization–

Visualization of phytosomes can be achived using transmission electron microscopy and scanning electron microscopy.

4.      Entrapment efficiency-

The entrapment efficiency can be measured by using ultracentrifugation technique.

5.      FTIR Spectrographic Analysis-

It is useful to determine structure and chemical stability of phytosomes.Spectral scanning may be done in the range between 4000-400cm-1.

6.      Surface tension activity measurement-

The surface tension activity of the drug in aqueous solution can be measured by the using various tensiometer.eg. Du Nouy ring tensiometer

7.      Drug content-

8.      The amount of drug can be quantified by modified HPLC method or by a suitable spectroscopic method.[11]

In vitro and In vivo evaluation-

These evaluations are based on therapeutic active phytoconstituents present in phytosomes. For example, in-vitro anti-hepatotoxic activity can be assessed by the antioxidant and free radical scavenging activity of phytosomes.

 

THERAPEUTIC APPLICATIONS OF PHYTOSOMES

1.      Curcumin phytosomes-

Meriva curcumin phytosome is unique curcumin extract that is significantly better absorbed than other curcumin extracts.Phytosomes are plant extracts bound to phosphatidylcholine(PC),an essential component of human cells.Our bodies can make PC but we can also get it from food or supplements.

Phytosomes of curcumin having better antioxidant property(4).

 

2.      Phytosomes of grape seed-

Procyanidine from grape seed extract is the main phytoconstituents which having better antioxidant property.Green tea rich in polyphenols and phytosome process binds the green tea extract to phosphatidylcholine for rapid and effective absorption, increasing bioavailability.

 

3.      Phytosomes of Gingko biloba-

Gingko biloba phytosomes contains 24% gingko flavones glycoside and 6% terpenes lactones.Its improved oral bioavailability and good tolerabilitymakes it the ideal gingko products even for long term treatment.Antioxidant capacity the improved efficacy of gingko phytosomes in combating the allergen induced bronchospam.[3]

 

4.      Sinigrin phytosomal complex-

Sinigrin having the better wound healing activity .The sinigrin phytosomal complex shows complete recovery of wound 100% and the phytoconstitute alone displayed only 71%healing.[3]

 

5.      Phytosomes of Arjuna Bark –

Phytosomes of Arjuna bark shows antiproliferative activity on human breast cancer cell line MCF-7by MTT assay by comparing its activities with Quercetin and its phytosomes.

 

6.      Panax ginseng phytosomes-

Phytosomal complex of panax ginseng helpful in preparation of dermatological and cosmetic pharmaceutical formulations shows moisturizing effect. Also it more active in vasal protection, capillary permeability, protection against UV radiation [4].

 

 

CONCLUSION:

Phytosomes are novel compounds comprising of lipophilic complexes of components of various plants like Silybum Marianum, Ginkgo Biloba, ginseng etc with phospholipids. Preparation of phytosomes is usually carried out by non conventional method. Absorption of phytosome in gastro intestinal tract is appreciably greater resulting in increased plasma level than the individual component. The drugs of ayurvedic origin can be utilized in a better form with enhanced efficacy by incorporating in modern dosage forms. However, phytotherapeutics need a scientific approach to deliver the components in a novel manner to increase patient compliance and avoid repeated administration. This can be achieved by designing novel drug delivery systems for herbal constituents. Novel drug delivery systems not only reduce the repeated administration to overcome non-compliance, but also help to increase the therapeutic value by reducing toxicity and increasing the bioavailability and so on. Recently, pharmaceutical scientists have shifted their focus to designing a drug delivery system for herbal medicines using a scientific approach. The novel research can also aid in capturing as well as to remain in the market. But there are many challenges with herbal drugs which need to be overcome like difficulty of conducting clinical research in herbal drugs, development of simple bioassays for biological standardization, pharmacological and toxicological evaluation methods’ development, investigation of their sites of absorption, toxic herbal drugs in use, discovering various animal models for toxicity and safety evaluation, legal and regulatory aspects of herbal drugs and so on.

 

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Accepted on 25.08.2018          © A&V Publications All right reserved