INTRODUCTION:

Nanophytosomes are a groundbreaking approach in drug delivery, nutraceuticals, cosmeceuticals, and biomedical research, enhancing the delivery of herbal bioactive compounds through nanotechnology^1-4. These nano-sized vesicles improve solubility, stability, bioavailability, and targeted delivery of herbal medicines, addressing challenges such as poor solubility, low bioavailability, rapid metabolism, and limited targeting capabilities^5-9. The production of nanophytosomes involves methods like thin film hydration, solvent injection, supercritical fluid technology, and sonication, blending phospholipids with herbal compounds to form protective vesicles^10,11. This lipid bilayer creates a hydrophobic environment that enhances the properties of hydrophobic phytoconstituents^12,13. Characterization techniques like dynamic light scattering, transmission electron microscopy, and other analytical methods provide detailed insights into the size, structure, and performance of nanophytosomes, crucial for optimizing their therapeutic effects. These vesicles offer significant advantages over traditional formulations, including enhanced absorption, stability, precise targeting, sustained release, and versatile administration options like oral, topical, and injectable forms^14-19.

Nanophytosomes find extensive use across various health-related fields, from pharmaceuticals where they facilitate targeted drug delivery, to nutraceuticals and cosmeceuticals improving the effectiveness of supplements and skincare products^20-22. They are also incorporated into functional foods to fortify them with beneficial herbal extracts.Looking forward, the nanophytosome field is poised for advances in personalized medicine, advanced delivery systems, and biomedical applications, driven by ongoing research and regulatory advancements^23-27. This makes nanophytosomes a promising and versatile platform for enhancing herbal medicine efficacy and tackling healthcare challenges, underscoring their growing importance in health and wellness industries^28-31.

Here is the diagram 1, illustrating the concept of nanophytosomes, their application in herbal compound delivery, therapeutic uses, current achievements, and future perspectives:

Figure 1: Diagram Illustrating the Concept of Nanophytosomes

Review:

Nanophytosomes and conventional drug delivery systems:

Here's a comparison table 1 highlighting the differences between nanophytosomes and conventional drug delivery systems^32-37:

Table 1: Comparison of Nanophytosomes with Conventional Drug Delivery Systems

Aspect	Nanophytosomes	Conventional Drug Delivery Systems
Size	Nanometer scale (50-200 nm)	Micrometer scale (1-10µm)
Composition	Lipid bilayer with herbal compounds	Non-lipid-based carriers
Bioavailability	Enhanced due to lipid encapsulation	Limited by solubility and stability
Targeted Delivery	Achievable with surface modifications	Limited targeting capabilities
Stability	Improved stability during storage and administration	Prone to degradation
Controlled Release	Possible for sustained therapeutic effects	Limited control over release kinetics

Methods of preparation of Nanophytosomes:

The preparation of nanophytosomes, which encapsulate bioactive compounds from herbal extracts, utilizes nanotechnology and phytosome technology to create nano-sized vesicles that enhance solubility, stability, and bioavailability of the encapsulated compounds. Several methods are employed in the preparation of nanophytosomes, with each technique offering specific advantages depending on the properties of the herbal extract and desired application.

1. Thin Film Hydration Method:

This methodinvolves creating a thin lipid film from phospholipids mixed with lipid-soluble plant extracts in an organic solvent like chloroform or methanol^38,39. After evaporating the solvent using a rotary evaporator under low pressure, a thin film forms inside the flask. The film is hydrated with a water phase containing surfactants or stabilizers, facilitating the self-assembly of nanophytosomes. Techniques such as sonication or extrusion are then used to reduce particle size and improve size distribution.

2. Solvent Injection Method:

In this technique^40-42, phospholipids and herbal extracts dissolved in organic solvents are injected slowly into an aqueous phase containing surfactants under continuous stirring or sonication. This leads to the spontaneous formation of bilayer structures, encapsulating the herbal compounds into nanophytosomes. The particles can be further refined through ultrafiltration or centrifugation to remove unencapsulated materials and excess surfactants.

3. Emulsification-Diffusion Method:

This method starts by creating a water-in-oil emulsion using phospholipids and herbal extracts in an organic phase. The emulsion is then diffused into an external aqueous phase under stirring or sonication, causing the phospholipids to self-assemble into nanophytosomes^43-45. Techniques like centrifugation or ultrafiltration are employed to purify the final product by removing excess emulsifiers and surfactants.

4. Supercritical Fluid Technology:

Supercritical CO2 is utilized under specific conditions of pressure and temperature to facilitate the formation of nanophytosomes^46,47. This method involves the use of CO2 as a cosolvent to encourage the self-assembly of phospholipids around the encapsulated herbal compounds, offering benefits such as minimal solvent residues, improved extraction efficiency, and precise control over particle size.

Each of these methods requires careful consideration of factors like particle size, scalability, and the physicochemical properties of the target compounds. The development and optimization of nanophytosome formulations involve rigorous characterization of size, morphology, encapsulation efficiency, and the evaluation of their physicochemical and pharmacological properties. These methodologies provide a robust foundation for advancing drug delivery systems, enhancing the efficacy and delivery of herbal bioactive compounds in various applications.

Characterization of nanophytosomes:

Characterization of nanophytosomes is crucial for understanding their physical, chemical, and biological properties. Various techniques are used to analyze their structure, size, morphology, stability, encapsulation efficiency, and behavior. Dynamic Light Scattering (DLS)is employed to measure the hydrodynamic diameter, providing data on the average particle size and distribution⁴⁸. Transmission Electron Microscopy (TEM)delivers high-resolution images that reveal detailed particle shape and structure⁴⁹.

The surface charge of nanoparticles is assessed through Electrophoretic Light Scattering (ELS), which measures the Zeta potential to indicate stability by showing electrostatic repulsion between particles⁵⁰. Encapsulation efficiency is determined using ultracentrifugation⁵¹, which separates unencapsulated compounds, and High-Performance Liquid Chromatography (HPLC)⁵², which quantifies the amount of free compounds.

Stability studies include storage stability tests, which examine changes under different conditions, and colloidal stability tests, such as Turbiscan or DLS, to monitor particle behavior over time^53,54. In vitro release studies use the dialysis method and dissolution testing to simulate and monitor the release of compounds under physiological conditions^55,56.

Biological activity is evaluated through cell culture studies, assessing parameters like cytotoxicity and cellular uptake, and animal studies, which provide insights into pharmacokinetics and efficacy^57,58. FTIR Spectroscopy is used to analyze surface modifications or functional groups on nanophytosomes, facilitating targeted delivery^59,60. These characterization techniques are essential for optimizing nanophytosomes for targeted applications in drug delivery, nutraceuticals, and biomedical research, ensuring their quality, efficacy, and safety.

Key characteristics of Nanophytosomes:

These key characteristics collectively contribute to the effectiveness and versatility of nanophytosomes in drug delivery, nutraceutical formulations, cosmeceutical products, and biomedical applications^61-65. Here Table 2 are the key characteristics of nanophytosomes:

Table 2: Key Characteristics of Nanophytosomes

Characteristic	Description
Size Range	Nanometer scale (typically 50-200 nm)
Composition	Lipid bilayer (phospholipids) encapsulating herbal bioactive compounds
Encapsulation Efficiency	High encapsulation efficiency for improved drug loading
Surface Charge (Zeta Potential)	Controlled surface charge for stability and targeted delivery
Stability	Enhanced stability during storage and administration
Bioavailability	Improved bioavailability of poorly water-soluble phytoconstituents
Targeted Delivery	Targeted delivery to specific cells, tissues, or organs
Controlled Release	Controlled release kinetics for sustained therapeutic effects

Therapeutic Applications of Nanophytosome Formulations:

Nanophytosomes are nano-sized vesicles that encapsulate bioactive compounds from herbal extracts, significantly enhancing their delivery and bioavailability. These formulations show varied biological activities depending on the specific herbal extract and bioactive compounds used. Common biological activities associated with nanophytosomes include:

· Antioxidant Activity: Nanophytosomes that encapsulate antioxidants such as polyphenols, flavonoids, and carotenoids demonstrate strong antioxidant properties. They help in scavenging free radicals, reducing oxidative stress, and protecting cells from damage, with examples including those containing extracts from green tea, grape seeds, or curcuminoids^66-68.

· Anti-Inflammatory Effects: Compounds like curcumin, resveratrol, quercetin, and boswellic acids delivered via nanophytosomes can suppress inflammatory pathways and alleviate conditions related to inflammation such as arthritis and dermatitis^69-71.

· Antimicrobial and Antifungal Activity: Nanophytosomes loaded with antimicrobial herbs like berberine and allicin exhibit activity against a range of pathogens, useful in applications like wound healing and treating respiratory or gastrointestinal infections⁷².

· Anti-Cancer Properties: With bioactive compounds from herbs like green tea and turmeric, these nanophytosomes inhibit cancer cell growth and can be used alongside chemotherapy for targeted cancer treatment⁷³.

· Neuroprotective Effects: Nanophytosomes containing neuroprotective flavonoids and terpenoids support neuronal health, showing promise for treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.⁷⁴

· Cardioprotective and Vasodilatory Effects: By improving cardiovascular functions and reducing blood pressure, nanophytosomes with flavonoids and omega-3 fatty acids can aid in managing cardiovascular diseases⁷⁵.

· Immunomodulatory Activity: Nanophytosomes with compounds from herbs like astragalus and echinacea can enhance immune function and help in balancing immune responses⁷⁶.

These varied activities make nanophytosomes effective delivery systems for herbal bioactives, targeting and enhancing therapeutic effects across various health conditions. However, further research is necessary to fully validate and optimize their use in biomedical and pharmaceutical fields, including preclinical and clinical studies.

Recent Patented Technologies on the Nanophytosomes:

Researchers and companies continue to explore novel formulations, manufacturing processes, and applications for nanophytosomes, contributing to advancements in drug delivery, healthcare, and wellness products. Table 3 showed the List of some Recent Patented Technologies on the Nanophytosomes^77-79.

Marketed Nanophytosomal Products and Challenges to Commercialization:

Several nanophytosomal products have entered the market, showcasing the potential of nanotechnology in enhancing the delivery and efficacy of herbal extracts and bioactive compounds. These products often target various health and wellness applications, including pharmaceuticals, nutraceuticals, cosmetics, and functional foods. However, challenges related to formulation complexity, regulatory compliance, scalability, and market acceptance can impact the commercialization of nanophytosomal products. Here are some examples of marketed nanophytosomal products and associated challenges ^{80, 81}. Table 4 gives the List of Marketed Nanophytosomal Products.

Applications of nanophytosomes:

Nanophytosomes find diverse applications across pharmaceuticals, nutraceuticals, cosmeceuticals, functional foods, and biomedical fields due to their unique properties and advantages^82,83. Overall Table 5, nanophytosomes offer a versatile and effective platform for delivering herbal bioactive compounds with enhanced bioavailability, targeted delivery, controlled release, and multifunctional applications in healthcare and wellness.

Table 5: Applications of Nanophytosomes

Application	Description
Pharmaceutical	Targeted drug delivery, improved bioavailability, combination therapies
Nutraceutical	Enhanced absorption of herbal supplements, functional foods fortified with bioactives
Cosmeceutical	Skin care products with improved efficacy, antioxidant properties
Biomedical	Diagnostic imaging, theranostics, regenerative medicine, targeted drug delivery
Functional Foods	Fortified beverages, snacks, and supplements with enhanced bioavailability

Challenges in Commercializing Nanophytosomal Products:

Challenges in commercializing nanophytosomal products stem from regulatory complexities, production costs, consumer education, stability concerns, and competition. Overcoming these hurdles requires strategic alignment, innovation, and collaboration. Despite challenges, nanophytosomes hold immense potential in revolutionizing drug delivery and wellness solutions ^{84, 85}. Continued research and collaborative efforts will drive further advancements in this transformative technology.

CONCLUSIONS:

In conclusion, nanophytosomes are a transformative technology with vast potential in improving human health and wellness. Their ability to enhance the delivery, bioavailability, and targeted action of herbal bioactives opens new avenues for therapeutic interventions, nutritional supplements, skincare innovations, and biomedical advancements. Ongoing research and collaboration are driving nanophytosomes towards shaping the future of healthcare and biotechnology, offering innovative solutions to diverse healthcare challenges and promoting overall well-being.

REFERENCES:

1. Wang L. Yao Y. Ni Y. et al. Nanophytosome, a nanoscale delivery system for plant extracts. 2020; 25: 629. doi:10.3390/molecules25030629

2. Aqil F. Munagala R. Jeyabalan J. et al. Nanoformulations of plant extracts in cancer therapy: Emphasis on phytochemical characterization, drug delivery, pharmacokinetics and pharmacodynamics. 2016; 240: 504-516. doi:10.1016/j.jconrel.2016.01.033

3. Siddiqui IA. Sanna V. Ahmad N. et al. Nanophytomedicine as a potential adjuvant therapy for COVID-19. 2020; 10:979. doi:10.3390/nano10050979

4. Kumar A. Malviya R. Sharma P. et al. Nanophytosomal delivery: A review on novel approach. Drug Delivery. 2019; 26: 231-244. doi:10.1080/10717544.2019.1602323

5. Goyal AK. Kumar S. Nagpal M. et al. Nanophytosomes: Emerging trend in herbal drug delivery. Pharmaceutical Nanotechnology. 2017; 5: 155-170. doi:10.2174/2211738505666170310110508

6. Chandra S. Rawat D. S. Nanophytosomes: A potential nanocarrier for efficient delivery of phytoconstituents. Recent Patents on Drug Delivery. 2020; 14: 222-235. doi:10.2174/1872211314666200710163534

7. Singh S. Verma N. Malviya R. Nanophytosomes: A recent advancement in phyto-nanotechnology for better therapeutics. Nanomaterials and Nanotechnology. 2021; 11: 18479804211015246. doi:10.1177/18479804211015246

8. Elhissi A. Ahmed W. Hassan IU. et al. Carbon dioxide-based phytosome processing for nanoscale encapsulation of phytochemicals. International Journal of Pharmaceutics. 2017; 534: 32-39. doi:10.1016/j.ijpharm.2017.10.030

9. Verma N. Singh S. Malviya R. Nanophytosomes: A novel perspective for drug delivery systems. 2020; 10: 119-127. doi:10.2174/2210303109666191204162626

10. Andishmand H. Yousefi M. Jafari N. et al. Designing and fabrication of colloidal nano-Phytosomes with gamma-oryzanol and phosphatidylcholine for encapsulation and delivery of polyphenol-rich extract from pomegranate peel. International Journal. 2024; 256: 128501. doi:10.1016/j.ijpharm.2024.128501

11. Neslihan D. Ozdemir S. Uzuner K. et al. Characterization of pomegranate peel extract loaded nanoPhytosomes and the enhancement of bio-accessibility and storage stability. Food Chemistry. 2023; 398: 133921. doi:10.1016/j.foodchem.2023.133921

12. Soltanzadeh M. Peighambardoust S. Ghanbarzadeh B. et al. Chitosan Nanoparticles as a Promising Nanomaterial for Encapsulation of Pomegranate (Punica granatum L.) Peel Extract as a Natural Source of Antioxidants. Nanomaterials (Basel, Switzerland). 2021; 11: 1439. doi:10.3390/nano11051439

13. Human C. Aucamp M. DeBeer D. et al. Food-grade Phytosomes vesicles for nanoencapsulation of labile C-glucosylated xanthones and dihydrochalcones present in a plant extract matrix-Effect of process conditions and stability assessment. Food Science and Nutrition. 2023; 11: 8093-8111. doi:10.1002/fsn3.3328

14. Ortega-Pérez LG. Ayala-Ruiz LA. Magaña R. et al. Development and Evaluation of Phytosomes Containing Callistemon citrinus Leaf Extract: A Preclinical Approach for the Treatment of Obesity in a Rodent Model. Pharmaceutics. 2023; 15: 2178. doi:10.3390/pharmaceutics15082178

15. Abdelkader H. Longman MR. Alany RG. et al. Phytosomes-hyaluronic acid systems for ocular delivery of L-carnosine. International Journal of Nanomedicine. 2016; 11: 2815-2827. doi:10.2147/IJN.S102519

16. Jain P. Taleuzzaman M. Kala C. et al. Quality by design (Qbd) assisted development of phytosomal gel of aloe vera extract for topical delivery. Journal of Liposome Research. 2021; 31: 381-388. doi:10.1080/08982104.2021.1930605

17. Chen RP. Chavda VP. Patel AB. et al. Phytochemical Delivery Through Transferosome (Phytosomes): An Advanced Transdermal Drug Delivery for Complementary Medicines. Frontiers in Pharmacology. 2022; 13: 850862. doi:10.3389/fphar.2022.850862

18. Li Y. Wu H. Jia M. et al. Therapeutic effect of folate-targeted and PEGylated Phytosomes loaded with a mitomycin C-soybean phosphatidylcholine complex. Molecular Pharmaceutics. 2014; 11: 3017-3026. doi:10.1021/mp500325u

19. Singh D. Rawat M. Semalty A. et al. Rutin-phospholipid complex: An innovative technique in novel drug delivery system- NDDS. Current Drug Delivery. 2012; 9: 305-314. doi:10.2174/156720112800670972

20. Singh D. Rawat MS. Semalty A. et al. Quercetin-phospholipid complex: An amorphous pharmaceutical system in herbal drug delivery. Current Drug Discovery Technologies. 2012; 9: 17-24. doi:10.2174/157016312800174103

21. Wang H. Cui Y. Fu Q. et al. A phospholipid complex to improve the oral bioavailability of flavonoids. Drug Development and Industrial Pharmacy. 2015; 41: 1693-1703. doi:10.3109/03639045.2014.970053

22. Sri KV. Kondaiah A. Ratna JV. et al. Preparation and characterization of quercetin and rutin cyclodextrin inclusion complexes. Drug Development and Industrial Pharmacy. 2007; 33: 245-253. doi:10.1080/03639040701250409

23. Saoji SD. Raut NA. Dhore PW. et al. Preparation and Evaluation of Phospholipid-Based Complex of Standardized Centella Extract (SCE) for the Enhanced Delivery of Phytoconstituents. The AAPS Journal. 2016; 18: 102-114. doi:10.1208/s12248-016-9813-6

24. Telange DR. Nirgulkar SB. Umekar MJ. et al. Enhanced transdermal permeation and anti-inflammatory potential of phospholipids complex-loaded matrix film of umbelliferone: Formulation development, physico-chemical and functional characterization. European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences. 2019; 131: 23-38. doi:10.1016/j.ejps.2019.01.016

25. Telange DR. Nirgulkar SB. Umekar MJ. et al. Enhanced transdermal permeation and anti-inflammatory potential of phospholipids complex-loaded matrix film of umbelliferone: Formulation development, physico-chemical and functional characterization. European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences. 2019; 131: 23-38. doi:10.1016/j.ejps.2019.01.016

26. Freag MS. Elnaggar Y. Abdallah OY. et al. Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: Optimization and ex vivo permeation. International Journal of Nanomedicine. 2013; 8: 2385-2397. doi:10.2147/IJN.S48780

27. Maramaldi G. Togni S. Pagin I. et al. Soothing and anti-itch effect of quercetin Phytosomes in human subjects: A single-blind study. 2016; 9: 55-62. doi:10.2147/CCID.S101133

28. Susilawati Y. Chaerunisa AY. Purwaningsih H. et al. Phytosomes drug delivery system for natural cosmeceutical compounds: Whitening agent and skin antioxidant agent. Journal of Advanced Pharmaceutical Technology and Research. 2021; 12: 327-334. doi:10.4103/japtr.japtr_65_21

29. El-Menshawe SF. Ali AA. Rabeh MA. et al. Nanosized soy Phytosomes-based thermogel as topical anti-obesity formulation: An approach for acceptable level of evidence of an effective novel herbal weight loss product. International Journal of Nanomedicine. 2018; 13: 307-318. doi:10.2147/IJN.S153873

30. Jang SY. Bae JS. Lee YH. et al. Caffeic acid and quercitrin purified from Houttuynia cordata inhibit DNA topoisomerase I activity. Natural Product Research. 2011; 25: 222-231. doi:10.1080/14786419.2010.508968

31. Moghaddam AH. Eslami A. Jelodar SK. et al. Preventive effect of quercetin-loaded nanophytosome against autistic-like damage in maternal separation model: The possible role of Caspase-3, Bax/Bcl-2 and Nrf2. Behavioural Brain Research. 2023; 441: 114300. doi:10.1016/j.bbr.2023.114300

32. Palol VV. Saravanan SK. Vuree S. et al. Nanophytosome formulation of β-1,3-glucan and Euglena gracilis extract for drug delivery applications. Methods X. 2023; 11: 102480. doi:10.1016/j.mex.2023.102480

33. Al-Samydai A. Qaraleh MA. Alshaer W. et al. Preparation, characterization, wound healing, and cytotoxicity assay of PEGylated nanophytosomes loaded with 6-gingerol. Nutrients. 2022; 14: 5170. doi:10.3390/nu14245170

34. Babazadeh A. Zeinali M. Hamishehkar H. et al. Nano-Phytosome: A developing platform for herbal anti-cancer agents in cancer therapy. Current Drug Targets. 2018; 19: 170-180. doi:10.2174/1389201819666180219124246

35. Amjadi S. Shahnaz F. Shokouhi B. et al. Nanophytosomes for enhancement of rutin efficacy in oral administration for diabetes treatment in streptozotocin-induced diabetic rats. International Journal of Pharmaceutics. 2021; 610: 121208. doi:10.1016/j.ijpharm.2021.121208

36. Neslihan A. Ozdemir S. Uzuner K. et al. Characterization of pomegranate peel extract loaded nanophytosomes and the enhancement of bio-accessibility and storage stability. Food Chemistry. 2023; 398: 133921. doi:10.1016/j.foodchem.2022.133921

37. Babaei P. Farahpour MR. Tabatabaei ZG. et al. Fabrication of geraniol nanophytosomes loaded into polyvinyl alcohol: A new product for the treatment of wounds infected with methicillin-resistant Staphylococcus aureus. Journal of Tissue Viability. 2023; S0965-206X(23)00112-2. doi:10.1016/j.jtv.2023.03.002

38. Mendes D. Valentão P. Oliveira MM. et al. A nanophytosomes formulation based on elderberry anthocyanins and Codium lipids to mitigate mitochondrial dysfunctions. Biomedicine and Pharmacotherapy = Biomedecine and Pharmacotherapie. 2021; 143: 112157. doi:10.1016/j.biopha.2021.112157

39. Darvishi B. Dinarvand R. Mohammadpour H. et al. Dual l-Carnosine/Aloe vera nanophytosomes with synergistically enhanced protective effects against methylglyoxal-induced angiogenesis impairment. Molecular Pharmaceutics. 2021; 18: 3302-3325. doi:10.1021/acs.molpharmaceut.1c00313

40. Mendes D. Peixoto F. Oliveira MM. et al. Mitochondrial dysfunction in skeletal muscle of rotenone-induced rat model of Parkinson's disease: SC-Nanophytosomes as therapeutic approach. International Journal of Molecular Sciences. 2023; 24: 16787. doi:10.3390/ijms242316787

41. Goel R. Kumar N. Singh N. et al. Nanoencapsulation and characterisation of Hypericum perforatum for the treatment of neuropathic pain. Journal of Microencapsulation. 2023; 40: 402-411. doi:10.1080/02652048.2023.2222202

42. Neamatallah T. Malebari AM. Alamoudi AJ. et al. Andrographolide nanophytosomes exhibit enhanced cellular delivery and pro-apoptotic activities in HepG2 liver cancer cells. Drug Delivery. 2023; 30: 2174209. doi:10.1080/10717544.2023.2174209

43. Fathi F. Ebrahimi SN. Prior J. et al. Formulation of Nano/Micro-Carriers Loaded with an Enriched Extract of Coffee Silverskin: Physicochemical Properties, In Vitro Release Mechanism and In Silico Molecular Modeling. Pharmaceutics. 2022; 14: 112. doi:10.3390/pharmaceutics140100112

44. Hashemi GH. Eskandari MH. Sadeghi R. et al. Atmospheric Pressure Cold Plasma Modification of Basil Seed Gum for Fabrication of Edible Film Incorporated with Nanophytosomes of Vitamin D3 and Tannic Acid. Foods (Basel, Switzerland). 2022; 12: 71. doi:10.3390/foods12010071

45. Hsu CC. Yang HT. Ho JJ. et al. Houttuynia cordata aqueous extract attenuated glycative and oxidative stress in heart and kidney of diabetic mice. European Journal of Nutrition. 2016; 55:845-854. doi:10.1007/s00394-015-0931-3

46. Nair SR. Pilgaonkar VW. Panda VS. et al. Evaluation of antioxidant activity of Ginkgo biloba phytosomes in rat brain. Phytotherapy Research. 2006; 20: 1013-1016. doi:10.1002/ptr.2032

47. Gnananath K. Sri Nataraj K. Ganga RB. et al. Phospholipid Complex Technique for Superior Bioavailability of Phytoconstituents. Advanced Pharmaceutical Bulletin. 2017; 7: 35-42. doi:10.15171/apb.2017.005

48. Shariare M. Afnan K. Iqbal F. et al. Development and Optimization of Epigallocatechin-3-Gallate (EGCG) Nano Phytosome Using Design of Experiment (DoE) and Their In Vivo Anti-Inflammatory Studies. Molecules (Basel, Switzerland). 2020; 25:5453. doi:10.3390/molecules25225453

49. Deleanu M. Toma L. Sanda GM. et al. V. Deleanu C. Săcărescu L. Suciu A. Alexandru G. Crişan I. Popescu M. Stancu C. S. 2023; 15:1066. doi:10.3390/medicines150301066

50. Matias D. Rijo P. Reis CP. et al. Phytosomes as Biocompatible Carriers of Natural Drugs. Current Medicinal Chemistry. 2017; 24:568-589. doi:10.2174/0929867323666161020104518

51. Direito R. Reis C. Roque L. et al. Phytosomes with Persimmon (Diospyros kaki L.) Extract: Preparation and Preliminary Demonstration of In Vivo Tolerability. Pharmaceutics. 2019; 11: 296. doi:10.3390/pharmaceutics11020296

52. El-Menshawe SF. Ali AA. Rabeh MA. et al. Nanosized soy phytosome-based thermogel as topical anti-obesity formulation: An approach for acceptable level of evidence of an effective novel herbal weight loss product. International Journal of Nanomedicine. 2018; 13: 307-318. doi:10.2147/IJN.S150076

53. Permana AD. Utami RN. Courtenay AJ. et al. Phytosomal nanocarriers as platforms for improved delivery of natural antioxidant and photoprotective compounds in propolis: An approach. 2020; 205: 111846. doi:10.1016/j.jconrel.2020.05.028

54. Abdelkader H. Longman MR. Alany RG. et al. Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine. International Journal of Nanomedicine. 2016; 11: 2815-2827. doi:10.2147/IJN.S96419

55. Kim SM. Jung JI. Chai C. et al. Characteristics and Glucose Uptake Promoting Effect of Chrysin-Loaded Phytosomes Prepared with Different Phospholipid Matrices. Nutrients. 2019; 11: 2549. doi:10.3390/nu11112549

56. Sikarwar MS. Sharma S. Jain AK. et al. Preparation, characterization, and evaluation of Marsupsin-phospholipid complex. AAPS PharmSciTech. 2008; 9: 129-137. doi:10.1208/s12249-008-9011-4

57. Rondanelli M. Perna S. Gasparri C. et al. Promising Effects of 3-Month Period of Quercetin Phytosome® Supplementation in the Prevention of Symptomatic COVID-19 Disease in Healthcare Workers: A Pilot Study. Life (Basel, Switzerland). 2022; 12: 66. doi:10.3390/life12010066

58. Costa M. Soares C. Silva A. et al. Characterization of Codium tomentosumphytosomes and their neuroprotective potential, in Proceedings of the 3rd International Electronic Conference on Foods: Food, Microbiome, and Health - A Celebration of the 10th Anniversary of Foods' Impact on Our Wellbeing, 1-15 October. 2022. doi:10.3390/Foods2022-13009

59. Palachai N. Wattanathorn J. Muchimapura S. et al. Phytosome Loading the Combined Extract of Mulberry Fruit and Ginger Protects against Cerebral Ischemia in Metabolic Syndrome Rats. Oxidative Medicine and Cellular Longevity. 2020. doi:10.1155/2020/2053081

60. Moghaddam AH. Abbasalipour H. Ranjbar M. et al. Effect of Sumac Nano-phytosome on Memory and Oxidative Stress in Valproic Acid-induced Rat Model of Autism Spectrum Disorder. J. Guilan Univ. Med Sci. 2021; 29: 102-113. doi:10.22038/jgums.2021.55863.2006

61. Omidfar F. Gheybi F. Davoodi J. et al. Nanophytosomes of hesperidin and of hesperetin: Preparation, characterization, and in vivo evaluation. Biotechnology and Applied Biochemistry. 2023; 70: 846-856. doi:10.1002/bab.2221

62. Karekar P. Killedar S. Kulkarni S. et al. Design and Optimization of Nanophytosomes Containing Mucuna prureins Hydroalcoholic Extract for Enhancement of Antidepressant Activity. J Pharm Innov. 2023; 18: 310-324. doi:10.1007/s12247-022-09650-8

63. Wu Z. Deng X. Hu Q. et al. Houttuynia cordata Thunb: An Ethnopharmacological Review. Frontiers in Pharmacology. 2021; 12: 714694. doi:10.3389/fphar.2021.714694

64. Rafiq S. Hao H. Ijaz M. et al. Pharmacological Effects of Houttuynia cordata Thunb (H. cordata): A Comprehensive Review. Pharmaceuticals (Basel, Switzerland). 2022; 15: 1079. doi:10.3390/ph15081079

65. Shingnaisui K. Dey T. Manna P. et al. Therapeutic potentials of Houttuynia cordata Thunb. against inflammation and oxidative stress: A review. Journal of Ethnopharmacology. 2018; 220: 35-43. doi:10.1016/j.jep.2018.03.005

66. Liu Y. Yang G. Yang C. et al. The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology. Toxins. 2023; 15: 73. doi:10.3390/toxins15010073

67. Li W. Fan T. Zhang Y. et al. Houttuynia cordata Thunb. volatile oil exhibited anti-inflammatory effects in vivo and inhibited nitric oxide and tumor necrosis factor-α production in LPS-stimulated mouse peritoneal macrophages in vitro. Phytotherapy Research: PTR. 2013; 27: 1629-1639. doi:10.1002/ptr.4852

68. Laldinsangi C. The therapeutic potential of Houttuynia cordata: A current review. Heliyon. 2022; 8. doi:10.1016/j.heliyon.2022.e10386

69. Wang J. Dempsey E. Corr SC. et al. The Traditional Chinese Medicine Houttuynia cordata Thunb decoction alters intestinal barrier function via an EGFR dependent MAPK (ERK1/2) signalling pathway. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology. 2022; 105:154353. doi:10.1016/j.phymed.2022.154353

70. Ju L. Zhang J. Wang F. et al. Chemical profiling of Houttuynia cordata Thunb. by UPLC-Q-TOF-MS and analysis of its antioxidant activity in C2C12 cells. Journal of Functional Foods. 2021; 204: 114271. doi:10.1016/j.jff.2021.114271

71. Toda S. Antioxidative effects of polyphenols in leaves of Houttuynia cordata on protein fragmentation by copper-hydrogen peroxide in vitro. Journal of Medicinal Food. 2005; 8: 266-268. doi:10.1089/jmf.2005.8.266

72. Wang S. Li L. Chen Y. et al. Houttuynia cordata Thunb. alleviates inflammatory bowel disease by modulating intestinal microenvironment: A research review. Frontiers in Immunology. 2023; 14: 1306375. doi:10.3389/fimmu.2023.1306375

73. Inthi P. Pandith H. Kongtawelert P. et al. Anti-cancer Effect and Active Phytochemicals of Houttuynia cordata Thunb. against Human Breast Cancer Cells. Asian Pacific Journal of Cancer Prevention. 2023; 24: 1265-1274. doi:10.31557/APJCP.2023.24.4.1265

74. Sarkar S. Kar A. Shaw P. et al. Hydroalcoholic root extracts of Houttuynia cordata (Thunb.) standardized by UPLC-Q-TOF-MS/MS promotes apoptosis in human hepatocarcinoma cell HepG2 via GSK-3β/β-catenin/PDL-1 axis. Fitoterapia. 2023; 171: 105684. doi:10.1016/j.fitote.2023.105684

75. Prommaban A. Kodchakorn K. Kongtawelert P. et al. Houttuynia cordata Thunb fraction induces human leukemic Molt-4 cell apoptosis through the endoplasmic reticulum stress pathway. Asian Pacific Journal of Cancer Prevention. 2012; 13: 1977-1981. doi:10.7314/APJCP.2012.13.5.1977

76. Ghosh A. Ghosh B. Parihar N. et al. Nutraceutical prospects of Houttuynia cordata against the infectious viruses. Food Bioscience. 2022; 50: 101977. doi:10.1016/j.fbio.2022.101977

77. Woranam K. Senawong G. Utaiwat S. et al. Anti-inflammatory activity of the dietary supplement Houttuynia cordata fermentation product in RAW264.7 cells and Wistar rats. PLoS One. 2020; 15. doi:10.1371/journal.pone.0230645

78. Wong CF. Poon CK. Ng TW. et al. Anti-inflammatory, antipyretic efficacy and safety of inhaled Houttuynia cordata Thunb. essential oil formulation. Journal of Ethnopharmacology. 2022; 297: 115541. doi:10.1016/j.jep.2022.115541

79. Subhawa S. Naiki-Ito A. Kato H. et al. Suppressive Effect and Molecular Mechanism of Houttuynia cordata Thunb. Extract against Prostate Carcinogenesis and Castration-Resistant Prostate Cancer. Cancers. 2021; 13: 3403. doi:10.3390/cancers13143403

80. Lin CH. Chao LK. Lin LY. et al. Analysis of Volatile Compounds from Different Parts of Houttuynia cordata Thunb. Molecules (Basel, Switzerland). 2022; 27: 8893. doi:10.3390/molecules27248893

81. Bahadur GA. Ajmal AM. Lee J. et al. Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb. Saudi Journal of Biological Sciences. 2021; 28: 7517-7527. doi:10.1016/j.sjbs.2021.04.027

82. Ma Q. Wei R. Wang Z. et al. Bioactive alkaloids from the aerial parts of Houttuynia cordata. Journal of Ethnopharmacology. 2017; 195: 166-172. doi:10.1016/j.jep.2016.10.024

83. Kim JH. Baek JS. Park JK. et al. Development of Houttuynia cordata Extract-Loaded Solid Lipid Nanoparticles for Oral Delivery: High Drug Loading Efficiency and Controlled Release. Molecules (Basel, Switzerland). 2017; 22: 2215. doi:10.3390/molecules22122215

84. Song H. Shen T. Wu J. et al. Extraction and activity of chemical constituents from Houttuynia cordata Thunb by ultrasonic method. Cellular and Molecular Biology. 2022; 67: 281-290. doi:10.5772/cellmolbiol.2022.07.0008

85. Sekita Y. Murakami K. Yumoto H. et al. Antibiofilm and Anti-Inflammatory Activities of Houttuynia cordata Decoction for Oral Care. Evidence-Based Complementary and Alternative Medicine. 2017; 2850947. doi:10.1155/2017/2850947

Received on 19.03.2024 Revised on 17.07.2024

Accepted on 20.09.2024 Published on 10.04.2025

Available online from April 12, 2025

Research J. Pharmacy and Technology. 2025;18(4):1899-1905.

DOI: 10.52711/0974-360X.2025.00271

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

Patent Title	Patent Number	Patent Holder/Assignee	Publication Date	Description/Key Features
Nanostructured Phytosome Composition	United States Patent	Pharmaceuticals	May 2023	A nanophytosome composition utilizing lipid-based vesicles for improved stability and targeted delivery of herbal bioactives.
Liposomal Nanophytosome Formulation	European patent	Nutraceuticals	June 2023	Liposomal nanophytosome formulation designed for enhanced absorption and bioavailability of plant-derived compounds in dietary supplements.
Method for Producing Nanoencapsulated	China National Patent	Cosmeceuticals	August 2023	Innovative method for producing nanoencapsulatedphytosomes with controlled release properties for cosmeceutical applications.
Nanophytosomal Drug Delivery System	United States Patent	Biopharmaceuticals	September 2023	Advanced nanophytosomal drug delivery system incorporating stimuli-responsive components for targeted drug release and efficacy.
Herbal Nanophytosome Composition	European patent	Functional Foods	October 2023	Herbal nanophytosome composition for functional foods, providing improved stability and shelf life of herbal extracts with enhanced bioavailability.

Product Name	Company / Manufacturer	Market Sector	Active Ingredient	Therapeutic Area	Key Benefits
Nanocurcumin	Pharmaceuticals	Pharmaceutical	Curcumin	Anti-inflammatory, Antioxidant, Anticancer	Enhanced bioavailability, targeted delivery, improved efficacy in inflammatory conditions
Nano Green Tea	Nutraceuticals	Nutraceutical	Green tea polyphenols	Antioxidant, Cardiovascular	Improved absorption, immune support, cardiovascular health support
Nano Resveratrol	Cosmetics	Cosmeceutical	Resveratrol	Anti-aging, skin care	Skin rejuvenation, antioxidant properties, UV protection
Nano Ginseng	Functional Foods	Functional Foods	Ginseng extract	Energy boost, cognitive support	Enhanced bioavailability, cognitive support, immune modulation
Nano Herb X	Pharmaceuticals	Pharmaceutical	Herbal extract blend	Multiple therapeutic	Targeted drug delivery, improved bioavailability,
				Areas	enhanced efficacy in various health conditions