CHARACTERIZATION, EVALUATION OF CYTOTOXIC ACTIVITY ASSAY AND OPTIMIZATION OF NANOEMULSION DELIVERY SYSTEM FORMULAS OF TOMATO LYCOPENE (SOLANUM LYCOPERSICUM. L)

Authors

  • FARIDA RAHIM Doctoral Program, Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatera-25163, Indonesia, Faculty of Pharmacy, Perintis University, Padang, West Sumatera-25586, Indonesia
  • HENNY LUCIDA Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatera-25163, Indonesia https://orcid.org/0000-0002-1816-990X
  • VALDY FILANDO SARDI Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatera-25163, Indonesia, The Laboratory of Natural Resources of Sumatra (LBS), Universitas Andalas, Padang, West Sumatera-25163, Indonesia https://orcid.org/0009-0007-3655-5963
  • FRIARDI ISMED Faculty of Pharmacy, Universitas Andalas, Padang, West Sumatera-25163, Indonesia, The Laboratory of Natural Resources of Sumatra (LBS), Universitas Andalas, Padang, West Sumatera-25163, Indonesia https://orcid.org/0000-0002-6200-7502
  • ANDANI EKA PUTRA Faculty of Medicine, Universitas Andalas, Padang, West Sumatera-25163, Indonesia

DOI:

https://doi.org/10.22159/ijap.2025.v17s1.11

Keywords:

Tomato, Lycopene, Nanoemulsion, Cell viability, Physicochemical properties

Abstract

Objective: This study aimed to evaluate the cytotoxic effects of tomato lycopene, quantify its bioactive fraction, and formulate tomato lycopene into nanoemulsions.

Methods: Lycopene was fractionated using chloroform and purified using methanol. Tomato lycopene was identified using liquid chromatography-mass spectrometry and ultraviolet-visible spectrophotometry, with the content determined using thin-layer chromatography-densitometry. Cytotoxicity was assessed in T47d, DU145, and HeLa cells using the MTT assay. The composition of the oil phase (Virgin Coconut Oil), surfactant (Tween 80), cosurfactant (PEG 400), and the aqueous phase of the nanoemulsion base was determined using a pseudo ternary phase diagram. Tomato lycopene was added to the oil phase and mixed with other components by spontaneous titration. The nanoemulsions were characterized by determining droplet size, zeta potential, Poly Dispersity Index (PDI), transmittance, pH, density, and morphology using transmission electron microscopy.

Results: Needle-shaped crystals were obtained, with a retention factor of 17.32 min, m/z 535.4316 (calculated for C40H56), and maximum wavelengths of 457, 484, and 517 nm. The bioactive fraction (chloroform) comprised 866.68 mcg/ml lycopene. Increasing lycopene concentration was inversely proportional to T47d, DU145, and HeLa cell viability after 96 h of incubation. Six of the 54 base formulations produced transparent solutions (droplet size: 14.10–500.50 nm). Incorporating 0.1% tomato lycopene into the base generated physically stable nanoemulsions with spherical droplets exhibiting the following features: particle size, 13.37–82.52 nm; zeta potential, (-12.4)–(-5.66) mV; PDI, 0.0813–0.4247; transmittance, 96.18–99.14%; pH, 5.49–6.40; relative density, 1.049–1.067.

Conclusion: Tomato lycopene showed weak citotoxic on T47d, DU145, and HeLa cell line. Six nanoemulsions with good physicochemical properties were obtained as transparent yellow solutions. The optimized lycopene nanoemulsion formulation (TLN6) was confirmed at the compisition of 0,1% lycopene, 7% VCO, 50,4% Tween 80 and 12,6% PEG 400.

References

Arballo J, Amengual J, Erdman JW. Lycopene: a critical review of digestion, absorption, metabolism, and excretion. Antioxidants (Basel). 2021;10(3):342. doi: 10.3390/antiox10030342, PMID 33668703.

Chauhan K, Sharma S, Agarwal N, Chauhan B. Lycopene of tomato fame: its role in health and disease. Int J Pharm Sci Rev Res. 2011;10(1):99-115.

Trejo Solis C, Pedraza Chaverri J, Torres Ramos M, Jimenez Farfan D, Cruz Salgado A, Serrano Garcia N. Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. Evid Based Complement Alternat Med. 2013;2013:705121. doi: 10.1155/2013/705121, PMID 23970935.

Kong KW, Khoo HE, Prasad KN, Ismail A, Tan CP, Rajab NF. Revealing the power of the natural red pigment lycopene. Molecules. 2010;15(2):959-87. doi: 10.3390/molecules15020959, PMID 20335956.

Wang XD. Lycopene metabolism and its biological significance. Am J Clin Nutr. 2012;96(5):1214S-22S. doi: 10.3945/ajcn.111.032359, PMID 23053559.

Li D, Li L, Xiao N, Li M, Xie X. Physical properties of oil-in-water nanoemulsions stabilized by OSA-modified starch for the encapsulation of lycopene. Colloids and Surfaces a: Physicochemical and Engineering Aspects. 2018;552(483):59-66. doi: 10.1016/j.colsurfa.2018.04.055.

Ismed F, Putra DP, Arifa N. Phytochemical profiling and antibacterial activities of extracts from five species of sumatran lichen genus stereocaulon. Jordan J Pharm Sci. 2021;14(2):189-202.

Sardi VF, Astika A, Jalius IM, Ismed F. Quantification of mangiferin from the bioactive fraction of mango leaves (Mangifera indica L.) and evaluation of wound-healing potential. Jordan J Pharm Sci. 2023;16(3):595-606. doi: 10.35516/jjps.v16i3.652.

Myong Kyun R, Min Hee J, Jin Nam M, Woi Sook M, Sun Mee P, Jae Suk C. Un metodo simple para aislar licopeno, a partir de lycopersicon esculentum. Bot Sci. 2013;91(2):187-92. doi: 10.17129/botsci.413.

Boileau AC, Merchen NR, Wasson K, Atkinson CA, Erdman JW. Cis-lycopene is more bioavailable than trans-lycopene in vitro and in vivo in lymph-cannulated ferrets. J Nutr. 1999;129(6):1176-81. doi: 10.1093/jn/129.6.1176, PMID 10356083.

Handayani UF, Mahata ME, Rizal Y, Suliansyah I, Wizna W. Potensi dan peningkatan kualitas nutrisi buah tomat (Lycopersicon esculentum) afkir sebagai Pakan ternak unggas. JUPET. 2018;15(1):22. doi: 10.24014/jupet.v15i1.4279.

Perdomo F, Cabrera Franquiz F, Cabrera J, Serra Majem L. Influence of cooking procedure on the bioavailability of lycopene in tomatoes. Nutr Hosp. 2012;27(5):1542-6. doi: 10.3305/nh.2012.27.5.5908, PMID 23478703.

Chemat Djenni Z, Ferhat MA, Tomao V, Chemat F. Carotenoid extraction from tomato using a green solvent resulting from orange processing waste. J Essent Oil Bear Plants. 2010;13(2):139-47. doi: 10.1080/0972060X.2010.10643803.

Davis AR, Fish WW, Perkins Veazie P. A rapid spectrophotometric method for analyzing lycopene content in tomato and tomato products. Postharvest Biol Technol. 2003;28(3):425-30. doi: 10.1016/S0925-5214(02)00203-X.

Cefali LC, Cazedey EC, Souza Moreira TM, Correa MA, Salgado HR, Isaac VL. Antioxidant activity and validation of quantification method for lycopene extracted from tomato. J AOAC Int. 2015;98(5):1340-5. doi: 10.5740/jaoacint.14-151, PMID 26525253.

Ferenczi Fodor K, Renger B, Vegh Z. The frustrated reviewer-recurrent failures in manuscripts describing validation of quantitative TLC/HPTLC procedures for analysis of pharmaceuticals. J Planar Chromatogr Mod TLC. 2010;23(3):173-9. doi: 10.1556/JPC.23.2010.3.1.

Rahim F, Putra PP, Ismed F, Putra AE, Lucida H, Molecular Dynamics. Docking and prediction of absorption, distribution, metabolism and excretion of lycopene as protein inhibitor of Bcl2 and DNMT1. Trop J Nat Prod Res. 2023;7(7):3439-44.

Kerna AN. A global health preventive medicine overture: lycopene as an anticancer and carcinopreventive agent in the deterrence of cervical cancer liking lycopene. SM Prev Med Public Heal. 2018;2(1):1-5.

Teodoro AJ, Oliveira FL, Martins NB, Maia G de A, Martucci RB, Borojevic R. Effect of lycopene on cell viability and cell cycle progression in human cancer cell lines. Cancer Cell Int. 2012;12(1):36. doi: 10.1186/1475-2867-12-36, PMID 22866768.

Lindshield BL, Canene Adams K, Erdman JW. Lycopenoids: are lycopene metabolites bioactive? Arch Biochem Biophys. 2007;458(2):136-40. doi: 10.1016/j.abb.2006.09.012, PMID 17067545.

Weerapreeyakul N, Nonpunya A, Barusrux S, Thitimetharoch T, Sripanidkulchai B. Evaluation of the anticancer potential of six herbs against a hepatoma cell line. Chin Med. 2012;7(1):15. doi: 10.1186/1749-8546-7-15, PMID 22682026.

Kumar A, Kushwaha V, Sharma PK. Pharmaceutical microemulsion: formulation, characterization and drug deliveries across skin. Int J Drug Dev Res. 2014;6(1):1-21.

Nirmalayanti NL. Skrining berbagai jenis Surfaktan dan Kosurfaktan. Ilmu Multidispilin. 2021;1(3):158-66.

Lu GW, Gao P. Emulsions and microemulsions for topical and transdermal drug delivery. Handbook of non-invasive drug delivery systems; 2010. p. 59-94.

Lukic M, Pantelic I, Savic SD. Towards optimal ph of the skin and topical formulations: from the current state of the art to tailored products. Cosmetics. 2021;8(3). doi: 10.3390/cosmetics8030069.

Bali V, Ali M, Ali J. Study of surfactant combinations and development of a novel nanoemulsion for minimizing variations in bioavailability of ezetimibe. Colloids Surf B Biointerfaces. 2010;76(2):410-20. doi: 10.1016/j.colsurfb.2009.11.021, PMID 20042320.

Hinger D, Grafe S, Navarro F, Spingler B, Pandiarajan D, Walt H. Lipid nanoemulsions and liposomes improve photodynamic treatment efficacy and tolerance in CAL-33 tumor-bearing nude mice. J Nanobiotechnology. 2016;14(1):71. doi: 10.1186/s12951-016-0223-8, PMID 27716314.

Published

24-02-2025

How to Cite

RAHIM, F., LUCIDA, H., SARDI, V. F., ISMED, F., & PUTRA, A. E. (2025). CHARACTERIZATION, EVALUATION OF CYTOTOXIC ACTIVITY ASSAY AND OPTIMIZATION OF NANOEMULSION DELIVERY SYSTEM FORMULAS OF TOMATO LYCOPENE (SOLANUM LYCOPERSICUM. L). International Journal of Applied Pharmaceutics, 17(1), 75–81. https://doi.org/10.22159/ijap.2025.v17s1.11

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