INTRODUCTION:

The multi-targeted action and reduced side-effect profiles of herbal medications give them a special place in the medical field. However, their practical usage is limited by issues such poor solubility, low bioavailability, and gastrointestinal tract degradation. By creating molecular interactions between phospholipids and active phytoconstituents, phytosomes overcome these restrictions. Drug targeting, therapeutic efficacy, and controlled release are improved by nanophytomedicine, an interdisciplinary platform that combines nanotechnology with herbal medicine. The technological underpinnings of phytosomes and their developing application in nanophytomedicine are reviewed in this article^1,2.

Over 80% of people worldwide use herbal medicine for some form of primary healthcare, according to the WHO. However, oral bioavailability is a significant challenge because the majority of phytochemicals are lipophilic and poorly water-soluble. Furthermore, many active ingredients are quickly broken down by stomach and liver enzymes before they enter the bloodstream. Because of these restrictions, researchers are now looking into nanocarriers that can enhance pharmacokinetics and maintain phytochemical activity. Among the several alternatives, phytosomes provide a special fusion of ease of use, effectiveness, and biomimetic compatibility, which makes them ideal for commercialization³.

The integration of phytosome and nanophytomedicine technologies represents a promising advancement in enhancing the therapeutic potential of plant-based compounds. Traditional herbal remedies often face challenges such as poor solubility, low bioavailability, and instability, limiting their clinical effectiveness. By combining botanical power with nanotechnology, these advanced delivery systems improve the absorption, stability, and targeted delivery of phytochemicals. The aim of this approach is to bridge the gap between natural medicine and modern pharmaceutical science, optimizing the efficacy of herbal therapies. Applications of phytosome and nanophytomedicine formulations span a wide range of medical fields, including cancer therapy, anti-inflammatory treatments, skin care, cardiovascular health, and neuroprotection, offering safer, more efficient, and patient-friendly alternatives to conventional drugs^4,5.

Phytosome Technology: Structure and Preparation:

Standardized plant extracts are molecularly complexed with phospholipids, usually phosphatidylcholine, to produce phytosomes. Phospholipids' amphiphilic properties improve bioactives' absorption across lipid membranes. Methods of preparation include:

· Solvent evaporation: phospholipid and phytoconstituent are dissolved in an appropriate solvent, then evaporation occurs.

· Precipitating the complex by adding a non-solvent is known as anti-solvent precipitation

· Co-freezing the ingredients to improve yield and stability is known as "freeze-drying."

Each technique affects the final formulation's entrapment efficiency, zeta potential, and particle size⁶.

The complexation efficiency is significantly impacted by the phospholipid to phytoconstituent molar ratio. Higher lipid ratios result in greater encapsulation but may dilute the medication concentration; a common ratio is between 1:1 and 3:1. The choice of solvent system, temperature, and stirring speed all affect the formation of complexes. Ultracentrifugation is frequently used to measure encapsulation efficiency (%EE), which is then followed by spectrophotometric examination. Despite being expensive, supercritical fluid techniques provide solvent-free processing and are becoming more popular for environmentally friendly manufacturing^7,8.

Figure 1: Mechanism of phytosome formation and improved cellular uptake.

Characterization Techniques:

Thorough characterization is essential to ensure the consistency and effectiveness of the formulation:

· Particle Size and Zeta Potential are measured using Dynamic Light Scattering (DLS), as they play a key role in determining stability and absorption.

· Fourier-Transform Infrared Spectroscopy (FTIR) verifies the presence of hydrogen bonding between the phytoconstituent and phospholipid.

· Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) are used to identify alterations in crystallinity.

· Nuclear Magnetic Resonance (NMR) reveals molecular-level interactions.

· Scanning and Transmission Electron Microscopy (SEM/TEM) provide detailed images of surface structure and particle distribution⁹.

These analytical techniques are crucial for evaluating how the formulation behaves under physiological conditions.

FTIR spectra of phytosomes reveal shifts in the hydroxyl and carbonyl regions, indicating the presence of hydrogen bonding. DSC thermograms display modified melting patterns, pointing to the creation of a new chemical structure. XRD analysis demonstrates a decrease in the crystallinity of the phytoconstituent after complexation, which is associated with enhanced solubility. TEM typically reveals vesicles with spherical or elliptical shapes ranging from 100 to 400 nm. Stability testing is conducted by storing the phytosomes at 25 °C and 40°C with 60% relative humidity, and monitoring changes in particle size and zeta potential over a period of 3 to 6 months¹⁰.

Comparative Advantages Over Conventional Nanocarriers:

Phytosomes are Distinguished from other Nanocarriers by Several Advantages:

· Enhanced Bioavailability: Binding with phospholipids increases solubility and facilitates better systemic absorption.

· Greater Stability: The lipid-based structure shields active compounds from enzymatic and oxidative breakdown.

· Easier Production: Phytosomes are simpler to manufacture than liposomes or other nanoparticles, requiring fewer processing steps and stabilizing agents.

· Cost Efficiency: They offer scalability with relatively low production costs compared to polymer-based nanocarriers¹¹.

Unlike liposomes, which trap drugs within their core, phytosomes form molecular bonds between bioactives and the phospholipid layer, allowing for improved integration with cell membranes¹².

Figure 2: Comparison of curcumin bioavailability across various formulations.

Applications in Herbal and Modern Therapeutics:

Phytosome formulations have demonstrated effectiveness in a variety of therapeutic areas:

· Liver Protection: Siliphos® (silybin phytosome) offers enhanced protection for the liver.

· Anti-inflammatory and Antioxidant Treatment: Meriva® (curcumin phytosome) shows improved activity in managing inflammation.

· Weight Management: Greenselect® Phytosome (green tea extract) aids in metabolic health and weight control.

· Topical Applications: Phytosomes containing quercetin or grape seed extract offer better skin penetration than their free counterparts.

· Oncology: New formulations are being developed to target cancer pathways with phytochemicals that have improved bioavailability.

· Cardiovascular Health: Phytosomes made from hawthorn extract have demonstrated antihypertensive and cardioprotective effects in animal studies.

· Neurodegenerative Diseases: Bacopa monnieri phytosomes show enhanced memory retention and lower oxidative stress in Alzheimer’s disease models.

· Cosmeceuticals: Phytosomes made from licorice, green tea, and grape seed are used in topical anti-aging and pigmentation-reducing formulations.

These diverse applications highlight the potential of phytosomes in merging traditional herbal knowledge with modern therapeutic approaches¹³.

Regulatory Status, Patents, and Market Products:

Phytosome-based products are gaining recognition as dietary supplements in the US (under FDA-DSHEA) and as nutraceuticals in Europe and India. Although there are no specific pharmacopeial monographs for phytosomes, numerous international patents have been granted. Indena S.p.A, a leader in phytosome technology, holds several patents, including US Patent No. 5,246,716 for Silymarin Phytosome.

Some approved or marketed phytosome products include:

Table 2: Commercial Phytosome Products and Their Therapeutic Applications

Product	Active Ingredient	Therapeutic Use	Manufacturer
Meriva®	Curcumin	Treatment for osteoarthritis and inflammation	Indena S.p. A
Siliphos®	Silybin (Milk Thistle)	Liver protection	Indena S.p. A
Greenselect® Phytosome	Green Tea Extract	Weight management and antioxidant support	Indena S.p. A
Ginkgoselect®	Ginkgo Biloba Extract	Enhances memory function	Indena S.p. A

These products have been introduced to international markets as standardized herbal formulations, backed by clinical evidence demonstrating their effectiveness^14,15.

Industrial and Commercial Perspective:

The global market for phytopharmaceuticals is experiencing a growing demand for natural, safe, and effective alternatives to synthetic medications. According to Market Research Future, the herbal medicine market is projected to surpass USD 111 billion by 2030, with phytosome-based formulations representing a substantial portion of innovative product development. Leading companies such as Indena, PhytosomeLab, and Euromed have developed proprietary technologies and patents. These companies prioritize not only product innovation but also clinical validation and regulatory compliance. Most phytosome formulations are introduced as nutraceuticals or functional food supplements, particularly in markets like the U.S., Europe, and India¹⁶.

Challenges such as the cost of raw materials, variability in extraction processes, and the need for stringent quality control of herbal actives continue to hinder large-scale adoption. However, collaborations between the public and private sectors, increased funding for research and development, and government support for initiatives like AYUSH and herbal medicines are helping address these issues.

The flexibility of phytosome formulations available in tablets, capsules, gels, and transdermal patches provides the pharmaceutical industry with opportunities to expand its delivery methods. Additionally, the growing use of phytosomes in wellness areas such as anti-aging, immunity enhancement, and neuroprotection is broadening their market presence in both preventive and therapeutic fields¹⁷.

Challenges in Commercialization and Clinical Translation

Despite promising preclinical results, the commercialization of phytosomes faces several challenges:

· Lack of Regulatory Clarity: Phytosomes occupy a gray area between herbal and pharmaceutical classifications.

· Limited Clinical Trials: Most available evidence is based on preclinical studies or anecdotal reports.

· Reproducibility and Scale-Up: Achieving consistent quality during large-scale production remains a technical hurdle.

· Solvent Residues: Ensuring the safe removal of residual solvents and validating their absence is crucial for regulatory approval.

· Toxicological Evaluation: While phospholipids are generally recognized as safe (GRAS), the long-term safety of phytosomes, particularly for parenteral use, requires extensive investigation.

· Reproducibility Issues: Variability between batches, due to differences in the quality of plant extracts or phospholipid grades, can affect product consistency.

· ICH Compliance: Analytical methods must comply with ICH Q2 (R1) guidelines for accuracy, precision, linearity, and robustness.

Addressing these issues requires harmonizing regulatory standards and enhancing GMP (Good Manufacturing Practice) processes¹⁸.

Pharmacokinetics and Bioavailability of Phytosomes:

Pharmacokinetic studies consistently show that phytosomes enhance the systemic absorption of poorly bioavailable phytochemicals. For instance, silybin-phytosome complexes exhibit a 4-fold increase in the area under the curve (AUC) and a 2.5-fold increase in peak plasma concentration (Cmax) compared to free silybin. Similarly, Meriva® (curcumin-phytosome) has demonstrated higher plasma levels of curcumin in human trials. The interaction with phospholipids improves the diffusion of these compounds across lipid-rich cell membranes, reducing both first-pass metabolism and enzymatic breakdown.

Additionally, phytosomes provide extended circulation time in the bloodstream, enabling sustained release and ensuring consistent therapeutic effects. In contrast to traditional formulations, the enhanced bioavailability also allows for reduced dosing, minimizing the risk of side effects. These benefits make phytosomes a preferred option for the treatment of chronic inflammatory conditions, liver diseases, and age-related cognitive decline¹⁹.

Future Outlook:

Future advancements in phytosome technology may include:

· Multi-Component Phytosomes: Combining various plant extracts to achieve synergistic therapeutic effects.

· Targeted Delivery: Functionalizing the surface with ligands or antibodies for precise delivery to specific sites.

· Personalized Herbal Nanotherapy: Merging patient genomics and AI to tailor herbal nanoformulations to individual needs.

· Regulatory Integration: As more countries acknowledge phytosomes as established therapeutic systems, market approval processes are expected to become more streamlined.

Nanophytomedicine is poised for rapid growth, fueled by ongoing innovation and its integration with biomedical engineering²⁰.

Clinical Studies and Human Trials on Phytosomes:

Numerous clinical trials have confirmed the safety and effectiveness of phytosome-based formulations. In a randomized double-blind study, patients with osteoarthritis who were treated with Meriva® showed significant improvements in pain and mobility compared to those who received standard curcumin. Similarly, Siliphos® has been tested in patients with both alcoholic and non-alcoholic fatty liver disease, resulting in notable reductions in ALT and AST enzyme levels.

Greenselect® Phytosome, derived from green tea extract, has been evaluated in obese individuals, showing positive effects on weight loss and antioxidant levels. Additionally, Ginkgoselect® (Ginkgo biloba phytosome) demonstrated cognitive improvements in elderly patients suffering from mild dementia.

These clinical findings underscore the potential of phytosomes and reinforce their position in evidence-based phytotherapy. As more human trial data become available, phytosomes are expected to transition from being primarily nutraceuticals to mainstream therapeutic options²¹.

Emerging Technologies for Phytosome Delivery:

Recent advancements in delivery technologies have opened new avenues for enhancing the efficacy of phytosomes. One such innovation involves PEGylated phytosomes, where polyethylene glycol (PEG) is added to extend circulation time by avoiding the reticuloendothelial system (RES). This enhances bioavailability and enables the targeting of chronic conditions such as cancer and diabetes.

Another promising development is stimuli-responsive phytosomes, which release the drug only in response to specific physiological triggers like pH changes, temperature variations, or enzymes.

For instance, curcumin phytosomes coated with a chitosan-poly(N-isopropylacrylamide) complex have demonstrated targeted release in inflamed tissues.

Research is also underway on solid phytosomal tablets and orodispersible strips for oral delivery, specifically designed for pediatric and geriatric populations. These new formulations aim to enhance patient compliance and simplify administration.

Nano-conjugated phytosomes, which incorporate gold, silver, or magnetic nanoparticles, offer dual therapeutic and diagnostic capabilities (theranostic). This opens up new possibilities in precision medicine, particularly for cancer detection and treatment.

With the rise of 3D printing in pharmaceuticals, phytosomes could eventually be personalized into patient-specific dosage forms with programmable release profiles. While these technologies are still in the preclinical or experimental phase, they hold great potential for future commercialization in therapeutic applications ²².

CONCLUSION:

Phytosomes and nanophytomedicine hold immense promise in revolutionizing herbal therapies by converting them into clinically validated, patient-friendly treatments. With their improved absorption, targeted delivery, and enhanced patient compliance, phytosomes have the potential to transform the delivery of plant-based therapeutics. By bridging traditional herbal knowledge with modern pharmaceutical advancements, they signify a major step forward in creating safe, effective, and innovative phytopharmaceuticals.

REFERENCES:

1. Nirosha V., Gayathri V. Spravato (Esketamine). Asian Journal of Nursing Education and Research. 2023; 13(3):226-7.

2. Chandana Pasupuleti, Abdul Saleem Mohammad, Nuha Rasheed, Kathula Umadevi, Duggi Adilakshmi. Simultaneous Formulation, Estimation and Evaluation of Ofloxacin Microbeads. Asian J. Pharm. Ana. 2016; 6(3): 167-182.

3. Nuha Rasheed, Abdul Saleem Mohammad, Seema Farheen, Shaik Zubair. Simultaneous Formulation Development, Evaluation and Estimation of Innovative Controlled Release Tablets of Bosentan Formulated with Varied Polymers. Asian J. Pharm. Ana. 2016; 6(4): 235-245.

4. Soniya L. Kattyar, Pravin S. Patil, Sachin V. Patil, Satwashila S. Kadam. Phytosomes and Recent research on Phytosomal Drugs. Asian J. Pharm. Ana. 2022; 12(1):61-9.

5. Sambasiva Naik Nunsavathu, B. Thangabalan. A RP-HPLC approach to Bioanalytical Method Development and Validation: A Review. Asian Journal of Pharmaceutical Analysis. 2024; 14(1):47-0. Yanyu X, Song Y, Chen Z, Qin P. The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats. Int J Pharm. 2006; 307(1): 77–82. doi: 10.1016/j.ijpharm.2005.10.001.

6. Ashok A. Hajare, Vrushali A. Patil. Formulation and Characterization of Metformin Hydrochloride Floating Tablets. Asian J. Pharm. Res. 2012; 2(3): 111-117.

7. Bharti Ahirwar. Bioavailability study of Kankasava. Asian J. Pharm. Res. 2013; 3(1): 01-02.

8. Hiral A. Makadia, Ami Y. Bhatt, Ramesh B. Parmar, Ms. Jalpa S. Paun, H.M. Tank. Self-nano Emulsifying Drug Delivery System (SNEDDS): Future Aspects. Asian J. Pharm. Res. 2013; 3(1): 20-26.

9. Jagdish Jadhav, Dharmendra Mundhada, Rajesh Mujoriya. Formulation Development and Evaluation of Gastro-Retentive Drug (Torsemide) Delivery System for Diuretic Drug. Asian J. Pharm. Res. 2015; 5(3): 125-130.

10. Rajashri R. Kulkarni, Dipti G. Phadtare, Ravindra B. Saudagar. A Novel Approach Towards Nanosuspension. Asian J. Pharm. Res. 2015; 5(4): 186-194.

11. B.A. Bhairav, J.K. Bachhav, R.B. Saudagar. Review on Solubility Enhancement Techniques. Asian J. Pharm. Res. 2016; 6(3): 147-152.

12. Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcumin–phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm. 2007; 330(1–2): 155–163. doi: 10.1016/j.ijpharm.2006.09.025.

13. Khanzode MB, Tekade AR, Gattani SG, Surana SJ. Review on phytosomes: a novel drug delivery system. GSC Biol Pharm Sci. 2020; 13(1): 203–211. doi:10.30574/gscbps.2020.13.1.034.

14. Indena S.p.A. Complexes of silybin with phospholipids having improved bioavailability. US patent US5246716A. Issued September 21, 1993. Accessed July 9, 2025.

15. Krishnaswami V, et al. Phytosomes, an emerging platform for herbal-based drug delivery. Nanobioletters. 2025; 14(1): 1–18. doi:10.33263/LIANBS141.029.

16. World Health Organization. WHO general guidelines for methodologies on research and evaluation of traditional medicine 2013–2023. Geneva: World Health Organization; 2013. ISBN: 9789241506090.

17. Rasool BK, Al Mahri N, Alburaimi N, Abdallah F, Shamma ASB. A narrative review of the potential roles of lipid-based vesicles (vesiculosomes) in burn management. Sci Pharm. 2022; 90:39. doi:10.3390/scipharm90030039.

18. Alharbi WS, Almughem FA, Almehmady AM, Jarallah SJ, Alsharif WK, Alzahrani NM, Alshehri AA. Phytosomes as an emerging nanotechnology platform for the topical delivery of bioactive phytochemicals. Pharmaceutics. 2021; 13:1475. doi:10.3390/pharmaceutics13091475.

19. Barani M, Sangiovanni E, Angarano M, Rajizadeh MA, Mehrabani M, Piazza S, Gangadharappa HV, Pardakhty A, Mehrbani M, Dell’Agli M. Phytosomes as innovative delivery systems for phytochemicals: a comprehensive review of literature. Int J Nanomedicine. 2021; 16: 6983–7022. doi:10.2147/IJN.S318416.

20. Kumar A, Kumar B, Singh SK, Kaur B, Singh S. A review on phytosomes: novel approach for herbal phytochemicals. Asian J Pharm Clin Res. 2017;10(10):42.

21. Gandhi A, Dutta A, Pal A, Bakshi P. Recent trend of phytosomes for delivering herbal extract with improved bioavailability. J Pharmakon Phytochem. 2012; 1(4): 6.

22. Amin T, Bhat S. A review on phytosome technology as a novel approach to improve the bioavailability of nutraceuticals. Int J Online Adv Res Technol. 2012; 1:1–15.

Received on 20.08.2025 Revised on 22.09.2025

Accepted on 24.10.2025 Published on 31.01.2026

Available online from February 07, 2026

Res. J. Pharmacognosy and Phytochem. 2026; 18(1):62-67.

DOI: 10.52711/0975-4385.2026.00010

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Parameter	Phytosomes	Liposomes	Polymeric Nanoparticles
Drug Incorporation Method	Binding with phospholipid	Trapping in an aqueous or lipid core	Adsorption or encapsulation
Stability	High (due to strong molecular bonds)	Moderate (prone to leakage)	High
Bioavailability Boost	Excellent	Moderate	Excellent
Toxicity	Low (composed of generally safe ingredients)	Moderate (depends on lipid source)	Varies (depends on polymer used)
Manufacturing Difficulty	Simple	Moderate	Complex
Market Presence	Wide range of products	Limited to a few herbal options	Few commercially available products

Phytosome and Nanophytomedicine:

A Brief Overview of Bridging Botanical Power with Nanotechnology