INTRODUCTION:

Plants plays a major role in maintaining and improving human health as well as quality of human life it is important ingredients in medicines, drinks, cosmetics, and colours. As a result, plant science is receiving more attention globally. The extracts and isolated components from medicinal and herbal plants have demonstrated interesting biological activity. From the ancient time the plant formulation are widely used and till continue to use. Oral route is most common route for administration of drug in the body. Large number of herbal drug are available but they are restricted because of their poor oral bioavailability and poor oral absorption. The bioavailability of a medicine can be enhanced by developing a drug delivery system that can quicken and expand drug absorption through lipid membranes^1,2. The outdated and antiquated drug administration mechanism utilised to give any herbal medicine to a patient who is ill reduces the effectiveness of the medication³.

A revolutionary drug delivery approach introduced to disperse the medication during the duration of treatment at a pace set by the body’s requirements. It also transports a bioactive chemical to the site of action⁴. Extracted constituents from the natural origin of plant have been found to have a positive pharmacological effect in the lab but a negative in vivo absorption. Numerous options are available to improve absorption and bioavailability of compound such as liposome, nanoparticles, emulsion as well as some modification in the chemical structure of constituent and delivery of prodrug, phyto-phospolipids complex known as phytosomes having ability to enhance the bioavailability and absorption⁵. Water soluble phytoconstituents are enable to pass through biological membranes due to size results in low bioavailability and absorption⁶.

Phytosomes:

In past few years phytochemicals are used as a potential therapeutics, but they also passes limitations of poor bioavailability and selectivity. Different methods can be used to increase the bioavailability of phytochemicals. To improve bioavailability, the phyto-phospolipids complex (also known as phytosomes) is a fantastic tool⁷. Phytosomes (or herbosomes) are liquid compatible phospholipid complex in nano form which provide coating or surrounds the active constituents. Due to this the active constituent from herbal extract remain unharmed by degredation⁸. Because the active ingredients in plant extracts are protected from degradation by peptic secretions and intestinal bacteria’s, the phytosome process results in a tiny cell. Important pharmacokinetic and pharmacodynamic characteristics of phytosomes make them useful for treating inflammation and acute and chronic liver disease⁹.

Advantages of phytosomes¹⁰:

· It assures proper delivery to targeted tissue.

· Dose requirement reduced bye maximum absorption of constituent.

· The primary component of a herbal extract is shielded by phytosomes from gut bacteria and digestive secretions.

· Enhance bioavailability of the drug.

· They are more effective than liposomes in skin care.

· They have significantly greather clinical benefits.

Flavonoids:

Plants contain polyphenolic substances called flavonoids. These are frequently used and serve numerous purposes. Flavonoids and other phenolic chemicals are typically found in leaves and other woody plant like stems and barks. They are essential for plant’s healthy growth, defence, and resistance to infection and damage. One definition of phytochemicals is "substances found in fruits and vegetables that may modulate human metabolism favourably for the prevention of chronic diseases and degenerative diseases." The most crucial pigments for floral colour are flavonoids, which give petals their yellow or red/blue pigmentation. They are secondary metabolites with antioxidant, anti-cancer, anti-inflammatory, anti-microbial, and nephrotoxicity protective properties. These flavonoids have a 15-carbon phenolic structure with two benzene rings, designated as "ring A and B." flavonoids having different pharmacological activities such as anticancer, wound healing, anti-oxidant, hepatoprotective, immunomodulatory, anti-inflammatory anti-viral, neuroprotective, cardiovascular diseases. Fruits, vegetables, cereals, barks, roots, stems, flowers, tea, and wine all contain flavonoids¹¹.

Anticancer activity of different flavonoids:

Cancer is caused by the uncontrolled rapid production of cells and impaired cell cycle which lead abnormal growth of cells which results invension and metastasis in various parts of the body. Frequent mutation, immune response resistance, persistent inflammation, angiogenesis induction, metastasis formation, altered metabolism, and disrupted cell cycle are only a few of the characteristics of cancer cells¹². By the various analysis of clinical studies, researchers get potential anticancer activity of flavonoids in diverse cell system

Phytosomal Flavonoids having anticancer activity:

1.Cyanidin 3-O-glucoside¹³

2.Epigallocatechin-3-gallate¹⁴

3.Genistein¹⁵

4.Luteolin¹⁶

5.Diosmetin¹⁷

6.Indirubin¹⁸

7.Xanthone¹⁹

8.Chrysoerion²⁰

9.Quercetin 3-O-D-galactopyranoside²¹

10.Nobiletin²²

11.Silybin A²³

Method for preparation of Phytosomes:-

Phospholipid +Organic solvent

Addition of plant extract

Evaporation +Film Development

Hydration of Film

Development of Phytosome Suspension

Sepration and Precipitation

Drying (Lyophilization)

Techniques of phytosomes preparation:

1. Mechanical dispersion method:

This technique involves dissolving lipid in an solvent before bringing it into contact with an water soluble phase that contains the medication²⁴. The next step is withdrawing solvent upon the pressure resulting in phytophospholipid compound.

2. Solvent evaporation method:

The phytoconstituents and PC containing organic solvent are integrated during solvent evaporation. To ensure maximum drug intrapment within the newly created phytosome, this reaction is conducted at a temperature of 40°C for a period of one hour.

3. Anti-solvent precipitation process:

Under the specified conditions, between 50°C-52°C for 2-4hours, a certain quantity of plant extract and phospholipid is dissolved in 20ml of an organic solvent. The reaction mixture is concentrated to a minimum volume of up to 10ml, at which point precipitate is produced by stirring in a solvent with low polarity, such as n-hexane. Desiccators are used to store filtered precipitates. The finely ground dry precipitates are kept in specified glass bottle at temperature²⁵.

CONCLUSION:

This review gives a general overview of phytosomes, including their history and how they are made. The collection of papers demonstrates the general benefits of using these formulations to increase the bioavailability of active phytochemicals. Also includes anticancer flavonoids which can form phytosomes.

REFERENCES:

1. Swati soman, R.K.Sharma, Varsha Sharma, Vidhi Gautam, K.Shrman, Rituraj Kewat and Savleen Kour, Phytosomes - A Novel Approach for Herbal Drug Delivery. Journal of Animal Research: 2020;10(4):479-485.

2. Chauhan, R.S., et al. Chemical Composition of Essential Oils in Mentha spicata L. Accession [IIIM(J)26] from North-West Himalayan Region, India. Industrial Crops and Products, 2009; 29: 654-656. http://dx.doi.org/10.1016/j.indcrop.2008.12.003.

3. Kamini Kashyap et al. Phytosomes: innovative drug delivery system for effectively delivering bioactive phytoconstituents and plant extracts. World Journal of Pharmaceutical and Medical Research. WJPMR, 2021, 7(5), 77-84.

4. K. Charana Sriya, Dividevara Sai, P. Ravi Sankar Phytosomes: A Novel Approach for Herbal Phytochemicals for Enhancing the Bioavailability Int. J. Pharm. Sci. Rev. Res. 2020; 60(2): 21-26

5. Lu, M., Qiu, Q., Luo, X., Liu, X., Sun, J., Wang, C., Song, Y. Phyto-phospholipid complexes (phytosomes): A novel strategy to improve the bioavailability of active constituents. Asian Journal of Pharmaceutical Sciences. 2018. doi:10.1016/j.ajps.2018.05.011 10.1016/j.ajps.2018.05.011.

6. Anila Suryakant Kadu, Madhavi Apte, Phytosome: A Novel Approach to Enhance the Bioavailability of Phytoconstituent. Asian Journal of Pharmaceutics. 2017; 11 (2): S453.

7. Mahmood Barani, Enrico Sangiovanni, Marco Angarano, Mohammad Amin, Rajizadeh Mehrnaz, Mehrabani4 Stefano, Piazza Hosahalli, Veerabhadrappa, Gangadharappa, Abbas Pardakhty, Mehrzad Mehrbani, Mario Dell’Agli, Mohammad Hadi, Nematollahi et al., Phytosomes as Innovative Delivery Systems for Phytochemicals: A Comprehensive Review of Literature. International Journal of Nanomedicine. 2021:16.

8. Kumar, A., Kumar, B., Singh, S. K., Kaur, B., and Singh, S. A review on phytosomes: novel approach for herbal phytochemicals. Asian Journal of Pharmaceutical and Clinical Research. 2017; 10(10): 41. doi:10.22159/ajpcr.2017.v10i10.2042410.22159/ajpcr.2017.v10i10.20424

9. Nilesh Jain, Brahma P Gupta, Navneet Thakur, Ruchi Jain, Jitendra Banweer, Deepak Kumar Jain, Surendra Jain et al. Phytosome: A Novel Drug Delivery System for Herbal Medicine . International Journal of Pharmaceutical Science and Drug Research. 2010; 2(4):224-228.

10. Sanjay Saha, Anupam Sarma, Pranjal Saikia, Tapash Chakrabarty. Phytosome: A brief overview. Scholars Academic Journal of Pharmacy (SAJP). 2013; 2(1):12-20

11. Hardeep Singh Tuli, Vivek Kumar Garg , Sakshi Bhushan, Vivek Uttam, Uttam Sharma, Aklank Jain, Katrin Sak, Vikas Yadav et al. Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer: A signature step hinting towards clinical perfection translational. Oncology. 2023; 27: 101596.

12. Kopustinskiene, Jakstas, Savickas, & Bernatoniene. (2020). Flavonoids as Anticancer Agents. Nutrients, 12(2), 457. doi:10.3390/nu12020 457 10.3390/nu12020457

13. Olivas-Aguirre, F., Rodrigo-García, J., Martínez-Ruiz, N., Cárdenas-Robles, A., Mendoza-Díaz, S., Álvarez-Parrilla, E., … Wall-Medrano, A. Cyanidin-3-O-glucoside: Physical-Chemistry, Foodomics and Health Effects. Molecules. 2016; 21(9): 1264. doi:10.3390/molecules21091264

14. Nagle, D. G., Ferreira, D., and Zhou, Y.-D. Epigallocatechin-3-gallate (EGCG): Chemical and biomedical perspectives. Phytochemistry. 2006; 67(17): 1849–1855. doi:10.1016/j.phytochem.2006.06.020

15. Tiantian Tian, Jisheng Li et al. Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small-cell lung cancer cells Tumor Biol. 2014; 35: 4137–4145. https://doi.org/10.1007/s13277-013-1542-0

16. Prasher, P., Sharma, M., Singh, S.K. et al. Luteolin: a flavonoid with a multifaceted anticancer potential. Cancer Cell Int. 2022; 22: 386. https://doi.org/10.1186/s12935-022-02808-3

17. Choi, J., Lee, D.-H., Park, S.-Y., and Seol, J.-W. Diosmetin inhibits tumor development and block tumor angiogenesis in skin cancer. Biomedicine and Pharmacotherapy. 2019; 117: 109091. doi:10.1016/j.biopha.2019.109091

18. Rahiminejad, A., Dinarvand, R., Johari, B., Nodooshan, S. J., Rashti, A., Rismani, E., Khosravani, M. Preparation and investigation of Indirubin-loaded SLN nanoparticles and their anti-cancer effects on human glioblastoma U87MG cells. Cell Biology International. 2018 doi:10.1002/cbin.11037

19. Akao, Y., Nakagawa, Y., & Nozawa, Y. Anti-Cancer Effects of Xanthones from Pericarps of Mangosteen. International Journal of Molecular Sciences. 20008; 9(3): 355–370. doi:10.3390/ijms9030355

20. Salari N, Faraji F, Jafarpour S, Faraji F, Rasoulpoor S, Dokaneheifard S, Mohammadi M. Anti-cancer Activity of Chrysin in Cancer Therapy: a Systematic Review. Indian J Surg Oncol. 2022; 13(4): 681-690. doi: 10.1007/s13193-022-01550-6. Epub 2022 May 10. PMID: 36687219; PMCID: PMC9845454.

21. Reyes-Farias, M., and Carrasco-Pozo, C. The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism. International Journal of Molecular Sciences. 2019; 20(13): 3177. doi:10.3390/ijms20133177

22. Ashrafizadeh, M., Zarrabi, A., Saberifar, S., Hashemi, F., Hushmandi, K., Hashemi, F., Garg, M. Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways. Biomedicines. 2020; 8(5): 110. doi:10.3390/biomedicines8050110

23. Ramasamy, K., and Agarwal, R. Multitargeted therapy of cancer by silymarin. Cancer Letters. 2008; 269(2): 352–362. doi:10.1016/j.canlet.2008.03.053

24. Sikarwar, M. S., Sharma, S., Jain, A. K., and Parial, S. D. Preparation, Characterization and Evaluation of Marsupsin–Phospholipid Complex. AAPS Pharm Sci Tech. 2008; 9(1): 129–137. doi:10.1208/s12249-007-9020-x

25. Vishal Gaurav, Shivangi Paliwal, Arpita Singh, Swarnima Pandey, Mohd. Aqil Siddhiqui. Phytosomes: Preparation, Evaluation and Application. International Journal of Research in Engineering and Science. 2021; 9(2): 35-39

Received on 27.05.2023 Modified on 29.06.2023

Asian J. Res. Pharm. Sci. 2023; 13(4):343-346.

DOI: 10.52711/2231-5659.2023.00059