Crescent College of Pharmaceutical Sciences, Kannur, Kerala, India.
Herbal medicines are widely used across the world due to their safety, cultural acceptance, and significant therapeutic potential. However, poor bioavailability remains a major limitation for many phytoconstituents. Most plant-derived active compounds, including flavonoids, glycosides, polyphenols, tannins, and alkaloids, exhibit low absorption and reduced systemic availability because of their large molecular size, poor lipid solubility, and limited membrane permeability. As a result, higher doses are often required to achieve therapeutic effects, which may reduce patient compliance. Phytosome technology has emerged as an advanced drug delivery system designed to overcome these challenges by complexing phytoconstituents with phospholipids, thereby improving their compatibility with biological membranes. The formation of a phospholipid–phytoconstituent complex enhances absorption, increases bioavailability, improves stability, and prolongs therapeutic activity. This review highlights the fundamental concept of phytosomes, various preparation methods, characterization techniques, advantages, limitations, and diverse applications in herbal drug delivery. Additionally, recent advancements and commercially available phytosomal formulations are discussed to emphasize their growing significance in modern phytopharmaceutical research.
Herbal drug products have gained significant attention due to their potential therapeutic benefits and minimal side effects compared to conventional synthetic drugs. However, the bioavailability of these herbal compounds is often limited due to their poor solubility and absorption. Phytosomes, a novel drug delivery system, have emerged as a promising solution to these challenges by enhancing the bioavailability and therapeutic efficacy of herbal drugs. This innovative approach involves the encapsulation of herbal extracts with phospholipids, forming complexes that improve solubility and absorption. The importance of phytosomes in herbal drug formulation can be understood through several key aspects.
While phytosomes offer significant advantages in herbal drug delivery, challenges remain in standardizing quality control methods and ensuring consistent production. Further research and development in this area could enhance the reliability and effectiveness of phytosomal formulations, potentially revolutionizing the field of herbal medicine delivery systems.
Phytosomes are innovative lipid-based nanovesicles in which standardized plant extracts or isolated polyphenolic phytochemicals are molecularly complexed with phospholipids, predominantly phosphatidylcholine, through hydrogen bonding between the polyphenolic moieties and the phosphate–choline head group. This interaction produces self?assembled vesicular systems structurally related to liposomes, encapsulating active phytoconstituents within a lipid environment and thereby overcoming the intrinsic hydrophilicity and membrane?permeation barriers of many glycosides and flavonoids. By improving compatibility with lipid-rich biological membranes, phytosomes markedly enhance the permeability, bioavailability, and therapeutic efficacy of enclosed plant components and are now regarded as efficient nanocarrier systems for oral and topical delivery of phytochemicals in diverse indications, including cancer and other chronic disorders.6,7,8,9
Figure 1: Structure of Phytosome10
Table: 1 Difference between Phytosomes and Liposomes
|
Feature |
Phytosomes |
Liposomes |
Citation |
|
Basic nature |
Molecular complex of phytochemical with phospholipid |
Closed phospholipid bilayer vesicle |
9,11 |
|
Main purpose |
Enhance solubility, permeability and bioavailability of herbal phytochemicals |
General carrier for many hydrophilic and lipophilic drugs |
9,11,12 |
|
Drug location |
Phytochemical closely associated with/complexed to phospholipid (improves membrane affinity) |
Drug dissolved in aqueous core or within bilayer, not necessarily complexed |
7,13 |
|
Typical cargo |
Plant polyphenols and other phytochemicals (e.g., silymarin, quercetin) |
Small?molecule drugs, peptides, nucleic acids, extracts, etc. |
9,11,14 |
|
Bioavailability effect |
Often produces large increases in oral or topical bioavailability vs. free extract |
Improves delivery but effect depends strongly on formulation and drug |
9,14 |
|
Stability & release |
Good interaction with phytochemicals; release can be faster than liposomes |
Often higher physical stability with slower release |
13 |
|
Example applications |
Meriva®(Curcumin Phytosome) used for Anti-inflammatory, joint health, and antioxidant support |
Doxil® (Doxorubicin HCl Liposome Injection for Treatment of ovarian cancer, AIDS-related Kaposi's sarcoma, and multiple myeloma. |
15,16 |
4. COMPONENTS OF PHYTOSOME
Phytosomes are formed by hydrogen bonding between the polar head of the phospholipid and polar groups (–OH, –COOH, –NH?) of the phytoconstituent2,21,22
5. METHODS OF PREPARATION OF PHYTOSOMES FOR HERBAL DRUG DELIVERY
Phytosomes are prepared by reacting herbal extracts or purified phytoconstituents with phospholipids (mainly phosphatidylcholine) in suitable organic solvents, then removing the solvent and processing the resulting phyto?phospholipid complex into a dosage form. The main methods used for herbal drug delivery are solvent evaporation / thin?film hydration, anti?solvent precipitation, solvent ether injection, co?solvent lyophilization / freeze?drying and spray?drying6,27–30
In the solvent evaporation / thin film method, the extract and phospholipid are dissolved in a common organic solvent (e.g., methylene chloride, dioxane, ethanol), often in a 1:1 or 1:2 molar ratio, then the solvent is removed under reduced pressure to form a thin film or solid complex that can be hydrated to give phytosomal vesicles6,29,31 This is the most commonly reported technique for phytosomes of silymarin, ginkgo, green tea, and many other herbal drugs 2,6,32
In anti solvent precipitation, the extract–phospholipid solution in a miscible organic solvent is added to a non solvent (e.g., n hexane), leading to precipitation of the complex, which is then filtered and dried28,30,31
Solvent ether (or solvent) injection involves injecting an organic solution of phospholipid and phytoconstituent into an aqueous phase, where rapid diffusion of solvent induces spontaneous formation of nano sized phytosomes 27,28
To improve stability and handling, these primary complexes can be further processed by freeze drying or co solvent lyophilization, in which the organic solvent is removed and the dispersion is lyophilized, often with cryoprotectants27–29
Spray drying or vacuum drying are also used to obtain free flowing phytosomal powders suitable for solid oral dosage forms. 29,30Choice of method affects particle size, entrapment efficiency, yield and release behaviour, and is selected according to the herbal drug’s solubility and the intended route (oral, topical, transdermal).28,33,34
For herbal phytosome products, characterisation focuses on confirming complex formation, nanosystem quality, and in vitro performance.
1. Basic physicochemical characterisation
Core critical quality attributes:
Dynamic light scattering is routinely used to determine mean size and polydispersity; size strongly influences stability, skin/oral absorption and biodistribution2,9,35
Indicates electrostatic stability; sufficient magnitude (positive or negative) helps prevent aggregation and predicts shelf stability and behavior at biological interfaces 2,35,36
Transmission and scanning electron microscopy (TEM/SEM) provide information on vesicle shape, surface, and uni-/multilamellar structure, important for release behavior and stability.2,9,37
FTIR, DSC, NMR and X ray diffraction are used to confirm interactions (H bonding, ionic interactions) between phytoconstituents and phospholipids and to distinguish true phytosomes from simple physical mixtures.9,19,37
2. Encapsulation and drug loading
Quantified (typically by HPLC/UV) after separating free drug (dialysis, ultracentrifugation); EE% is a key indicator of formulation success and strongly affects dose and bioavailability.9,35,36
3. In vitro performance tests
Dialysis or diffusion studies in biorelevant media are used to determine release kinetics; sustained or improved release vs. crude extract is usually targeted.9,12,35
Monitoring size, PDI, zeta potential, EE%, and chemical integrity over time under different temperatures, pH, and light conditions evaluates physical/chemical stability and suitability for scale up.2,9,36,38
4. Biological evaluation (preclinical/clinical)
Cell or skin models (for topical) and Caco 2/intestinal models (for oral) assess enhanced permeability versus plain extracts.7,9,39
Animal or human studies measuring Cmax, AUC, and t½ show consistently higher systemic exposure for phytosomes of curcumin, silymarin, quercetin and others compared with non complexed extracts.6,9,24,29
Disease specific models (anti inflammatory, anticancer, hepatoprotective, metabolic, etc.) compare efficacy and required dose versus conventional herbal formulations.8,9,12,24
Cytotoxicity assays and in vivo toxicity profiles confirm that phospholipid complexes remain biocompatible and do not introduce new adverse effects relative to the parent herb.24,36,38
Phytosomes are phospholipid–plant extract complexes designed to overcome poor bioavailability of many herbal actives.
Advantages
Limitations and challenges
A number of phytosome?based herbal products are already commercialized, mainly through the Indena “phytosome/ herbosome/ planterosome” platforms and similar technologies.
Table 2: Representative marketed phytosome products and indications.
|
Product / trade name |
Main herb / active |
Main indication / use |
Citations |
|
Siliphos (silybin phytosome) / Legalon SIL, Silipide |
Silybum marianum (silymarin/silybin) |
Hepatoprotection in chronic liver disease, toxic liver injury, NAFLD; improved oral bioavailability vs. plain silymarin |
9,39,44 |
|
Meriva / Curcumin phytosome |
Curcuma longa (curcumin) |
Anti?inflammatory and antioxidant; arthritis, joint pain, metabolic and cardiovascular support |
9,25,35 |
|
Greenselect / GreenSelect Phytosome |
Camellia sinensis (green tea catechins) |
Weight management, metabolic syndrome, antioxidant and cardiovascular support |
6,9,35 |
|
Ginkgoselect / Ginkgo biloba phytosome |
Ginkgo biloba extract |
Cognitive function, peripheral vascular disease, microcirculation |
6,9,45,46 |
|
Leucoselect / grape seed phytosome |
Vitis vinifera (proanthocyanidins) |
Cardiovascular protection, antioxidant, capillary fragility |
9,25,29 |
|
Mirtoselect / bilberry phytosome |
Vaccinium myrtillus (anthocyanins) |
Vision support, capillary health |
6,9 |
|
Boswellia phytosome (e.g. Casperome) |
Boswellia serrata acids |
Anti?inflammatory, osteoarthritis, IBD adjunct |
9,12,35 |
|
Ginseng, hawthorn, rutin, catechin phytosomes |
Panax ginseng, Crataegus spp., etc. |
Tonic, cardioprotective, antioxidant and cosmetic uses |
6,29,46 |
Across recent reviews, several converging directions are highlighted:
Overall, phytosomes are positioned as a maturing platform that already supports multiple marketed herbal products, with current research pushing toward nano?engineered, targeted and personalized phytosomal systems capable of meeting pharmaceutical regulatory standards.
CONCLUSION
Phytosome technology represents an important advancement in herbal drug delivery by overcoming key limitations of conventional formulations, such as poor solubility, permeability, and bioavailability of phytoconstituents. Complexation with phospholipids enhances the absorption, stability, and therapeutic efficacy of bioactive compounds like curcumin, silymarin, quercetin, and green tea polyphenols while maintaining safety due to the biocompatible nature of phospholipids. Phytosomes have demonstrated improved pharmacokinetic and pharmacodynamic profiles across various therapeutic applications, including hepatoprotection, inflammation, cancer, cardiovascular disorders, and cosmeceuticals, with several products already commercialized. Despite these advantages, challenges related to large-scale manufacturing, quality control, regulatory approval, and limited clinical evidence remain, highlighting the need for standardized production methods and well-designed clinical trials. Overall, phytosomes effectively bridge traditional herbal medicine and modern nanotechnology, offering a promising platform for future phytopharmaceutical and nutraceutical development
REFERENCES
Rahana Raveendran, Aswathi D, Kavya Raveendran, Aiswariya A, Aswathi P, Phytosome: Unlocking the Therapeutic Potential of Herbal Phytoconstituents, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 2, 4686-4696. https://doi.org/10.5281/zenodo.18817283
10.5281/zenodo.18817283