Phytosome: A Novel Drug Delivery System

 

Ashwini Natha Waghmode1, Amruta Anil Mali2, Dipali N. Hagir3

1,2Student, Navsahyadri Instituent of Pharmacy, Pune, Maharashtra, India.

3Guide, Navsahyadri Instituent of Pharmacy, Pune, Maharashtra, India.

*Corresponding Author E-mail: dipalihagir5@gmail.com

 

ABSTRACT:

Glycerophospholipids and plant-based components combine to generate lipid-compatible compounds in phytosomes, which are innovative delivery mechanisms. "Phyto" means plant-derived, and "some" means a structure that resembles a cell. Using this novel method, phospholipids can combine with water-soluble phytoconstituents or standardised herbal extracts to form molecular complexes that improve absorption and bioavailability.  By adding polyphenols to these phospholipid-based systems, the problems caused by their poor oral absorption are resolved. Phytosomes enhance gastrointestinal absorption and raise plasma concentrations of active substances by encasing hydrophilic herbal components in a lipophilic layer. The review underscores the growing function of phytosomes in augmenting the medicinal efficacy of herbal treatments and their diverse pharmaceutical formulations, including gels, pills, creams, and suspensions.

 

KEYWORDS: Phytosome, Novel drug delivery system, Phospholipids, Preparation, Application, Bioavailability, Characterization etc.

 

 


INTRODUCTION:

By enhancing the pharmacokinetic characteristics of natural chemicals, state-of-the-art medication delivery methods seek to increase their effectiveness. Phytosomes—also referred to as herbosomes in some texts—are such systems that incorporate water-soluble or standardized herbal extracts into lipid-compatible complexes to enhance absorption7. These systems form a bridge between conventional and advanced drug delivery approaches. The term "phyto" relates to plants, while "some" implies a cellular structure, symbolizing their role in mimicking biological cell interaction8.

 

 

In order to improve systemic transport and shield the extract from being broken down by digestive enzymes and gut bacteria, phytosomes help move active components from hydrophilic surroundings to the lipid-friendly membranes of enterocytes9,10. The optimal delivery mechanism maximises therapeutic results by releasing the medicine at the correct pace and focussing on the precise region of action11.

 

Structure of Phytosome:-

 

Fig 01: Structure of Phytosome

 

PROPERTIES OF PHYTOSOMES:

Physical Properties:

1.     The size of phytosomes varies according on their formulation characteristics, ranging from about 50 nm to several hundred micrometres12.

2.     According to nuclear magnetic resonance (NMR) investigations (¹H and ¹³C), the aliphatic chains of phospholipids maintain their chemical integrity and envelop the active ingredients in a protective lipophilic shell13.

3.      Frequently insoluble in water, these complexes have limited solubility in alcohol and high solubility in aprotic solvents. Curcumin is one example of a hydrophobic phytoconstituent that exhibits improved water solubility following complexation with phospholipids14,15.

4.     Phytosomes adopt the shape of liposomes in a hydrophilic environment. However, instead of being contained in an aqueous core like liposomes, the active components in phytosomes are bonded within the polar head of phospholipids16.

5.      By hydrogen bonding their polar functional groups, phospholipids and standardised herbal extracts form a complex in a stoichiometric process17.

6.     According to photon correlation spectroscopy (PCS), phytosomes disperse in water to create micelle-like vesicular structures that mimic liposomes18.

 

Chemical Properties:

1.     Hydrogen bonding is the main mechanism by which phytoconstituents bind to the polar heads of phospholipids, such as phosphate and ammonium groups, according to spectroscopic investigations 19.

2.     In nonpolar solvents and at stoichiometric ratios, the interaction is often conducted with natural phospholipids, such as those produced from soy 20.

3.     A stable complex is created when the plant extract and phospholipids combine in certain amounts, resulting in a structure with better hydrophilic and lipophilic balance 21.

 

Biological Properties:

1.     The systemic absorption and bioavailability of active phytoconstituents are enhanced by phytosomes in comparison to traditional herbal extracts22.

2.     They raise the concentration of substances available systemically and improve active absorption when taken orally23.

3.     These systems exhibit more reliable treatment outcomes and enhanced pharmacokinetics24.

4.     In herbal drug delivery, studies have demonstrated that the complexation enhances cellular permeability and membrane stability, making phytosomes a more efficient substitute for liposomes25.

 

 

METHOD OF PREPARATION OF PHYTOSOME:

In order to create phytosomes, phospholipids such soy lecithin are usually reacted with plant extracts in an aprotic solvent.  The active phytoconstituent and phosphatidylcholine, the two main constituents, combine to create a stable combination.  The extract's lipid component interacts with phosphatidyl, increasing stability and bioavailability, while the hydrophilic component attaches to the choline head26.

 

1.     Precipitation Method for Antisolvents:-Using this procedure, a mixture of soy lecithin and herbal extract is mixed in dichloromethane and refluxed at about 60°C for two hours. After concentration, the phytosome precipitates when n-hexane is introduced dropwise as an antisolvent while stirring. Under hoover, the product is filtered and dried. This process, which is patented, works well for creating complexes such as andrographolide–phospholipid combinations27,28

 

2.     The Gas Antisolvent Method (GAS):-Drug-phospholipid solutions are subjected to supercritical carbon dioxide as an antisolvent at regulated pressure and temperature in the GAS method. Fine precipitated phytosomes are the end product of this. The vessel is usually kept for several hours at 38°C and 10 MPa of pressure29.

 

3.     The Supercritical Fluid Method (SCF):-Using supercritical fluids like CO₂, this technique creates nanoparticles with a size range of 5–2000 nm. Complexes with improved solubility and stability are prepared using methods such as Solution Enhanced Dispersion by Supercritical Fluids (SEDS), Rapid Expansion of Supercritical Solutions (RESS), and Supercritical Antisolvent (SAS). SAS has been effectively utilised to synthesise puerarin–phospholipid complexes, for example30,31.

 

4.     Method of Rotary Evaporation:-This method involves mixing a water-miscible organic solvent, like acetone, with a specified amount of phospholipid and herbal extract in a round-bottom flask. At temperatures lower than 50°C, the mixture is agitated for two hours in a rotary evaporator. The complex is precipitated using antisolvents such as n-hexane once the solvent has been removed. The finished product is kept in amber-colored containers with regulated humidity levels32,33.

 

5.     The Lyophilization Process:-Dimethyl sulfoxide (DMSO) is used to dissolve the herbal extract, which is then combined with a phospholipid solution in t-butyl alcohol. After being mixed, the mixture is frozen and then freeze-dried. At 4°C, the resultant phytosome complex is kept in a desiccator. Phospholipid type, solvent, and ratio are among the variables that affect the final product's yield and properties34.

Mode of Action of Phytosomal Technology:

Because of their low lipid solubility and molecular structure, which restrict passive diffusion across biological membranes, many polyphenolic phytoconstituents, including flavonoids, have limited bioavailability35. These problems are resolved by phytosomal technology, which creates molecular complexes of polyphenols and phospholipids in a 1:1 or 1:2 molar ratio. Around the active ingredients, this structure creates a lipid-compatible coating that improves systemic availability and facilitates absorption through the gastrointestinal tract29. Therapeutic efficacy is increased because the lipid sheath shields the active ingredients from being broken down by gut microbes and digestive enzymes36.

 

Advantages of Phytosomes:

1.     Safe Composition: Phospholipids and herbal actives, among other phytosome ingredients, are widely acknowledged to be safe for use in pharmaceutical applications37.

2.     Preservation of Active Compounds: Phytosomes protect delicate herbal components from deterioration by intestinal bacteria activity and digestive juices38.

3.     Increased Bioavailability: By enabling the active ingredients to move from aqueous surroundings into enterocytes' lipophilic milieu and ultimately into the circulation, these systems greatly improve absorption 39.

4.     Targeted Delivery: Phytosomes' distinct physicochemical characteristics may allow for the site-specific administration of herbal medications, which could enhance therapeutic results 40.

 

Disadvantages of Phytosomes:

1.     Carcinogenic Potential: Some formulations may pose safety risks due to the potential for certain phospholipids, such lecithin, to promote the growth of particular cancer cell lines, such as MCF-7 breast cancer cells 41.

2.     Problems with Stability: Phytoconstituents may occasionally evaporate from the phospholipid complex, which could lead to unstable formulations and a decrease in medication concentration 42.

3.     Expensive Ingredients: Manufacturing high-purity natural phospholipids and solvents is more expensive, which could prevent widespread commercial use.

 


 

Difference Between Phytosome and Liposome:73,74

Table No: 1 Difference Between Phytosome and Liposome

Sr.

No

Phytosome

Liposome

1.

The polar or hydrophilic portion (head) of phospholipids interacts with a water-soluble plant extract to create phytosomes, which are then formed by chemical (hydrogen) bonding.

In the process of creating liposomes, phospholipids are combined with a water-soluble material; however, no chemical bonds are created.

2.

In phytosomes, depending on the plant extract employed, phospholipids and substrate complexes are generated in a stoichiometric ratio.

In liposomes, the material envelops hundreds of phospholipid molecules.

3.

By using phytosomes, a substance's bioavailability is improved and the absorption of phytoconstituents is increased.

Compared to phytosomes, liposomes are less effective at increasing the absorption of phytoconstituents and the bioavailability of substances.

4.

Because they generate phytophospholipid complexes, phytosomes are more stable than liposomes.

Since there is no chemical interaction and no complex is formed, liposomes are less stable than phytosomes.

5.

The dielectric constant has decreased due to the solvents employed in the manufacture of phytosomes.

The solvent in liposomes is either water or buffer solution.

6.

Phosphatidylcholine and the specific plant chemical in phytosomes combine to produce a 1:1 or 2:1 complex, depending on the ingredient.

The water-soluble molecule is encircled by hundreds of thousands of phosphatidylcholine molecules in liposomes.

 

Fig 02 Diffrence Between Phytosom and Liposome


 

CHARACTERIZATION OF PHYTOSOMES:

Particle size, membrane integrity, entrapment efficiency, and surface charge are some of the variables that affect how well phytosomes function and behave in biological systems. The methods listed below are used to assess these parameters:

1.     Entrapment Efficiency: Using ultracentrifugation techniques, the capacity of a phytosome to hold onto active phytoconstituents is evaluated. Next, it is measured how much of the active ingredient is trapped inside the lipid vesicles43.

 

2.     Visualisation: The surface morphology and vesicle production are confirmed using Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM)44,45.

 

3.     Vesicle Size and Zeta Potential: When combined with Photon Correlation Spectroscopy (PCS), Dynamic Light Scattering (DLS) yields data on the size distribution and zeta potential, which signify colloidal stability46,47.

 

4.     Evaluation by Spectroscopy: By examining upfield or downfield shifts in proton signals, ¹H NMR is used to verify complex formation. Changes in the phospholipid chains and choline group signify binding48.

 

Carbon bonding and interactions between phospholipid and phytoconstituent molecules are revealed by ¹³C NMR. Resonance peak changes verify the integrity of the complex49.

 

5.     Fourier Transform Infrared Spectroscopy: The functional groups of substances' free and complexed forms can be distinguished using Fourier Transform Infrared Spectroscopy, or FTIR. The complex development is supported by the elimination of free peaks and the creation of new links50.

 

6.     Evaluation in Vitro and In Vivo: Assays are chosen to evaluate biological activity based on the desired therapeutic impact. Animal studies are used for in vivo testing, whilst antioxidant and radical scavenging experiments are used in vitro to assess anti-hepatotoxic capabilities51.

 

7.     Drug Content: To guarantee precise drug loading, quantitative analysis is carried out using proven spectrophotometric techniques or High-Performance Liquid Chromatography (HPLC)52,53.

 

8.     Transition Temperature: Differential Scanning Calorimetry (DSC) aids in figuring out the phospholipid bilayer's phase transition temperature, which influences the stability of vesicles.

 

9.     Surface Tension Activity: The Du Noüy ring method determines the drug's surface activity in aqueous systems54,55.

 

10. Optical Microscopy: Using a light microscope, initial observations are conducted to examine the form and size of phytosome vesicles that have been created on a glass slide.

 

11. Pharmacological-Excipient Compatibility: FTIR is used to confirm suitability between the herbal extract and formulation excipients, guaranteeing that no unwanted chemical interactions take place56.

 

Phytosomal Formulation:57,63

Table No 02 Phytosomal Formulation

Sr.

No

Phytosome Name

Plant Source

Active Constituents

Therapeutic Application

1.

Silymarin Phytosome

Silybum marianum

Silymarin

Hepatoprotective

2.

Curcumin Phytosome

Curcuma longa

Curcumin

Anti-inflammatory, antioxidant

3.

Green Tea Phytosome

Camellia sinensis

Epigallocatechin gallate

Antioxidant, anti-obesity

4.

Ginkgo Phytosome

Ginkgo biloba

Flavonoid glycosides

Memory enhancement, cognitive support

5.

Grape Seed Phytosome

Vitis vinifera

Proanthocyanidins

Antioxidant, cardiovascular health

6.

Quercetin Phytosome

Various sources

Quercetin

Anti-inflammatory, liver protection

7.

Boswellia Phytosome

Boswellia serrata

Boswellic acids

Anti-arthritic, anti-inflammatory

 

APPLICATIONS OF PHYTOSOMES:

Because of their improved safety profile and distribution capabilities, phytosomes have been used in a variety of fields64.

1.     Improved Bioavailability: Phytosomes make poorly absorbed phytochemicals including flavonoids, terpenoids, and polyphenols more systemically available by increasing their solubility and membrane permeability65.

 

2.     Complex Drug Delivery: These systems can be used to deliver sensitive substances that are otherwise unstable or poorly absorbed in traditional formulations, such as proteins, peptides, and polyphenols66.

 

3.     Natural and Safe Composition: Phytosomes are safe for long-term use in herbal medicine and cosmetic formulations since they are made from naturally occurring, biocompatible phospholipids67

 

4.     Hepatoprotection: In silymarin, curcumin, and green tea extract formulations, phytosomes have demonstrated encouraging outcomes in liver protection treatments68.

 

5.     Cosmetics: Because of their capacity to permeate skin layers, they are perfect for topical formulations as sunscreen and anti-aging lotions69.

 

6.     Low Toxicity Risk: Phytosomes have a low toxicity profile, which makes them appropriate for oral and dermal applications, according to clinical trials70.

 

7.     Market Potential: In the pharmaceutical, nutraceutical, and cosmeceutical industries, phytosomes are highly attractive due to their therapeutic versatility and excellent patient compliance.

 

CONCLUSION:

An important development in the realm of herbal medication administration is phytosomes.  They fill the gap between conventional herbal medicines and contemporary therapeutic demands by improving the solubility, absorption, and bioavailability of plant-based chemicals 71.  The range of applications for these vesicular systems is increased by their ability to be applied topically as well as orally.  Further investigation in this field might reveal even more extensive medicinal advantages and creative applications of phytosomes in conventional medicine.  Phytosomes are anticipated to become a key component of the creation of phytopharmaceutical formulations as our knowledge of their action and safety advances 72.

 

ACKNOWLEDGEMENT:

Author grateful towards Dr. K. V. Otari Sir, Principal, and Navsahyadri Institute of Pharmacy for being a constant source of inspiration and support in all endeavors and providing all the facilities required for carrying out my project work. Also, author sincere thanks to the guide Dipali N. Hagir NIP. and Prof. Prachi Ghadage Madam, B. Pharm, Academic Co-ordinator and all the staff members who extended the preparatory steps of this dissertation.

 

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Received on 08.06.2025      Revised on 14.08.2025

Accepted on 22.09.2025      Published on 20.01.2026

Available online from January 27, 2026

Asian J. Pharm. Tech. 2026; 16(1):39-44.

DOI: 10.52711/2231-5713.2026.00007

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