Cosmos caudatus Kunth. Leaf Extract Herbal Nanosuspension Formulations, Characterization, and Cytotoxicity Approach Against MCF-7 Breast Cancer Cells
Abstract
Kenikir leaves (Cosmos caudatus Kunth.) contain quercetin, which has anticancer properties. To provide more effective complementary therapy for breast cancer, nanotechnology was applied to develop preparations containing kenikir leaf extract. This research aimed to formulate a nanosuspension containing kenikir leaf extract with cytotoxic activity against MCF-7 breast cancer cells. Nanosuspension of kenikir leaf extract was prepared using the ionic gelation method with 3%, 4%, and 5% PVP K-30 stabilizer. The nanosuspension formula with the highest entrapment efficiency was further characterised, including particle size, polydispersity index (PDI), zeta potential, pH, and particle morphology. Cytotoxic activity was tested against MCF-7 cells by the MTT assay. The results showed that the formula with 5% PVP has the highest entrapment efficiency value of 85.04±0.08%, a particle size of 221.9 nm, a PDI of 0.211, a zeta potential of -21.7 mV, a pH of 4.08±0.0, and a spherical morphology. The kenikir leaf extract at a concentration of 1 mg/mL inhibited the proliferation of MCF-7 cells by 23.4% (p<0.05), whereas the nanosuspension at 10 μg/mL inhibited proliferation by 23.7%. It can be concluded that kenikir leaf extract can be formulated into a nanosuspension that meets the physical criteria and has cytotoxic activity against MCF-7 cells.
References
1. Adawiyah R, Setiawan A, Nita S. Effect of active fraction of kenikir (Cosmos caudatus Kunth) leaf extract on cytotoxic test, apoptosis and antiproliferation of T47D breast cancer cells in vitro. Biomedical Journal of Indonesia. 2017;3(3):138-44.
2. Ezzati M, Yousefi B, Velaei K, Safa A. A review on anticancer properties of querce tin in breast cancer. Life sciences. 2020;248:117463.
3. Widiyantoro A, Harlia H. Antioxidant activity of leaves extract of kenikir (Cosmos caudatus Kunth) with various extraction methods. Indones J Pure Appl Chem. 2021;3(1):9-20.
4. Kasiri N, Rahmati M, Ahmadi L, Eskandari N, Motedayyen H. Therapeutic potential of quercetin on human breast cancer in different dimensions. Inflammopharmacology. 2020;28:39-62.
5. Andriani M, Permana IDGM, Widarta IR. The effect of time and temperature extraction on antioxidant activity of starfruit wuluh leaf (Averrhoa bilimbi L.) using ultrasonic assisted extraction (UAE) method. J. Ilmu dan Teknol Pangan. 2019;8(3):330–40.
6. Khan H, Ullah H, Martorell M, Valdes SE, Belwal T, Tejada S, Sureda A, Kamal MA. Flavonoids nanoparticles in cancer: Treatment, prevention and clinical prospects. Seminars in Cancer Biology. 2021;69:200-11.
7. Mudgil M, Gupta N, Nagpal M, Pawar P. Nanotechnology: a new approach for ocular drug delivery system. Int J Pharm Pharm Sci. 2012;4(2):105- 2.
8. Koczkur KM, Mourdikoudis S, Polavarapu L, Skrabalak SE. Polyvinylpyrrolidone (PVP) in nanoparticle synthesis. Dalton transactions. 2015;44(41):17883-905.
9. Pamungkas AR, Indrayudha P. Cytotoxic activity of ethanol, ethanol-water, ethyl acetate, and n-hexane extracts of Momordica charantia against mcf-7 cells in-vitro. Pharmacon: Jurnal Farmasi Indonesia. 2019;16(2):73-82.
10. Kemenkes RI. Farmakope Herbal Indonesia Edisi II. Jakarta: Kementrian Kesehatan RI. 2017.
11. Arba M, Susilawati Y, Mustarichie R. Hair growth promoting activity of langir bark (Albizia saponaria Lour.) ethanol extract: In-vivoASSAY. Rasayan Journal of Chemistry. 2022;15(3):2065-71.
12. Do QD, Angkawijaya AE, Tran-Nguyen PL, Huynh LH, Soetaredjo FE, Ismadji S, Ju YH. Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of Limnophila aromatica. Journal of Food and Drug Analysis. 2014;22(3):296-302.
13. Azizah DN, Kumolowati E, Faramayuda F. Determination of flavonoid content AlCl3 method in methanol extract of cocoa fruit (Theobroma cacao l.). Kartika Jurnal Ilmiah Farmasi. 2014;2(2):45-9.
14. Gayo Z, Lucida H, Zaini E. Solid dispersion of quercetin-PVP K-30 and its effects on the antioxidant activity. Jurnal Ilmiah Farmasi. 2020;16(2):144-54.
15. Thandapani G, Prasad S, Sudha PN, Sukumaran A. Size optimization and in vitro biocompatibility studies of chitosan nanoparticles. International Journal Of Biological Macromolecules. 2017;104:1794-806.
16. Sivasankarapillai VS , Das SS , Sabir F, Sundaramahalingam MA, Colmenares JC, Prasannakumar S, Rajan M, Rahdar A, Kyzas GZ. Progress in natural polymer engineered biomaterials for transdermal drug delivery systems. Materials Today Chemistry. 2021;19:100382.
17. Moon H, Lertpatipanpong P, Hong Y, Kim CT, Baek SJ. Nano-encapsulated quercetin by soluble soybean polysaccharide/chitosan enhances anticancer, anti-inflammation, and antioxidant activities. Journal of Functional Foods. 2021;87:104756.
18. Suciati T, Nafisa S, Nareswari TL, Juniatik M, Julianti E, Wibowo MS, Yudhistira T, Ihsanawati I, Triyani Y, Khairurrijal K. ArtinM. Grafted phospholipid nanoparticles for enhancing antibiotic cellular uptake against intracellular infection. International Journal of Nanomedicine. 2020;8829-43.
19. Arifin MF, Noviani Y, Nafisa S, Sheilabel A. Preparation, characterization, and optimization of ionic gelated nanoparticles dried extract of temulawak rhizome (Curcuma xanthorrhiza R.) using a factorial design 22. Jurnal Ilmu Kefarmasian Indonesia. 2022;20(2):272-80.
20. Wang X, Luo N, Xu Z, Zheng X, Huang B, Pan X. The estrogenic proliferative effects of two alkylphenols and a preliminary mechanism exploration in MCF‐7 breast cancer cells. Environmental Toxicology. 2020;35(5):628-38.
21. de Oliveira Gonçalves K, Vieira DP, Levy D, Bydlowski SP, Courrol LC. Uptake of silver, gold, and hybrids silver-iron, gold-iron, and silver-gold aminolevulinic acid nanoparticles by MCF-7 breast cancer cells. Photodiagnosis and Photodynamic Therapy. 2020;32:102080.
22. El-Atawy MA, Alsubaie MS, Alazmi ML, Hamed EA, Hanna DH, Ahmed HA, Omar AZ. Synthesis, characterization, and anticancer activity of new N, N′-Diarylthiourea derivative against breast cancer cells. Molecules. 2023;28(17):6420.
23. Utami NF, Sutanto S, Nurdayanty SM, Suhendar U. The effect of various methods of extraction on flavonoid levels flower leaf extract (Plenctranthus scutellariodes). FITOFARMAKA: Jurnal Ilmiah Farmasi. 2020;10(1):76-83.
24. Saini A, Panesar PS, Bera MB. Comparative study on the extraction and quantification of polyphenols from citrus peels using maceration and ultrasonic technique. Current Research in Nutrition & Food Science. 2019;7(3):678-85.
25. Rukmana RM, Sawal AA, Wibawa DA. Combination of antibacterial activity of ethanol extract of meniran leaves and kenikir leaves against Shigella dysenteriae. In1st International Conference for Health Research BRIN ICHR 2022. 2023;7-20.
26. Pakade VE, Lesaoana M, Tavengwa NT. Effect of pH, time and temperature on forced degradation studies of quercetin in presence of polymers. Asian Journal of Chemistry. 2016;28(10):2181-7.
27. Fadillah A, Rahmadani A, Rijai L. Analysis of total flavonoid levels and antioxidant activity test of kelubut leaf extract (Passiflora foetida L.). In Proceeding of Mulawarman Pharmaceuticals Conferences. 2017; 5: 21-8.
28. Jabbari M, Khosravi N, Feizabadi M, Ajloo D. Solubility temperature and solvent dependence and preferential solvation of citrus flavonoid naringin in aqueous DMSO mixtures: an experimental and molecular dynamics simulation study. RSC advances. 2017;7(24):14776-89.
29. Tamayo-Ramos JA, Martel S, Barros R, Bol A, Atilhan M, Aparicio S. On the behavior of quercetin+ organic solvent solutions and their role for C60 fullerene solubilization. Journal of Molecular Liquids. 2022;345:117714.
30. Alshehri S, Shakeel F, Alam P, Pena A, Jouyban A, Martinez F. Effect of temperature and polarity on the solubility and preferential solvation of sinapic acid in aqueous mixtures of DMSO and Carbitol. Journal of Molecular Liquids. 2021;340:117268.
31. Marudova M, Zahariev N, Milenkova S, Pilicheva B, Viraneva A, Yovcheva T. Development and in‐vitro characterization of benzydamine loaded chitosan nanoparticles. In Macromolecular Symposia. 2021;395(1):2000279.
32. Ranjit K, Baquee AA. Nanoparticle: an overview of preparation, characterization, and application. Int Res J Pharm. 2013;4(4):47-57.
33. Verma S, Kumar S, Gokhale R, Burgess DJ. Physical stability of nanosuspensions: Investigation of the role of stabilizers on ostwald ripening. Int J Pharm. 2011; 406(1- 2):45-52.
34. Goel S, Sachdeva M, Agarwal V. Nanosuspension technology: recent patents on drug delivery and their characterizations. Recent pat drug deliv formul. 2019; 13(2): 91–104.
35. Vecchi CF, Cesar GB, Souza PR, Caetano W, Bruschi ML. Mucoadhesive polymeric films comprising polyvinyl alcohol, polyvinylpyrrolidone, and poloxamer 407 for pharmaceutical applications. Pharmaceutical Development and Technology. 2021;26(2):138-49.
36. Bandulasena MV, Goran TV, Omololu GO, Brahim B. Continuous synthesis of PVP stabilized biocompatible gold nanoparticles with a controlled size using a 3D glass capillary microfluidic device. Chem Eng Sci. 2017; 171: 233–43.
37. Lakshmi P, Kumar GA. Nanosuspension technology: a review. Int J Pharm Pharm Sci. 2010;2(4):35-40.
38. Kusuma AW, Aries NN, Hartanti D. Cytotoxic and antiproliferative effects of quercetin on colon cancer cells WiDr. PHARMACY: Jurnal Farmasi Indonesia. 2010; 7(03):107-22
39. Oueslati MA, Gunenc A, Rigane G, Ghazghazi H, Valencia C, SALEM RB, Boukhchina S, Willmore WG, Hosseinian F. Chemical composition, antioxidant and cytotoxic activities of Onopordum acanthium L. crude oil and defatted meal. Rev. Roum. Chim. 2019;64(6):503-10.
40. Fauzia A, Wati UA, Rizkita CG, Qori’ah EW, Arifin I. The effect of marigold leaves and doxorubicin toward cell cycle and apoptosis of T47D cells. Indonesian Journal of Cancer Chemoprevention. 2016;7(3):79-86.
2. Ezzati M, Yousefi B, Velaei K, Safa A. A review on anticancer properties of querce tin in breast cancer. Life sciences. 2020;248:117463.
3. Widiyantoro A, Harlia H. Antioxidant activity of leaves extract of kenikir (Cosmos caudatus Kunth) with various extraction methods. Indones J Pure Appl Chem. 2021;3(1):9-20.
4. Kasiri N, Rahmati M, Ahmadi L, Eskandari N, Motedayyen H. Therapeutic potential of quercetin on human breast cancer in different dimensions. Inflammopharmacology. 2020;28:39-62.
5. Andriani M, Permana IDGM, Widarta IR. The effect of time and temperature extraction on antioxidant activity of starfruit wuluh leaf (Averrhoa bilimbi L.) using ultrasonic assisted extraction (UAE) method. J. Ilmu dan Teknol Pangan. 2019;8(3):330–40.
6. Khan H, Ullah H, Martorell M, Valdes SE, Belwal T, Tejada S, Sureda A, Kamal MA. Flavonoids nanoparticles in cancer: Treatment, prevention and clinical prospects. Seminars in Cancer Biology. 2021;69:200-11.
7. Mudgil M, Gupta N, Nagpal M, Pawar P. Nanotechnology: a new approach for ocular drug delivery system. Int J Pharm Pharm Sci. 2012;4(2):105- 2.
8. Koczkur KM, Mourdikoudis S, Polavarapu L, Skrabalak SE. Polyvinylpyrrolidone (PVP) in nanoparticle synthesis. Dalton transactions. 2015;44(41):17883-905.
9. Pamungkas AR, Indrayudha P. Cytotoxic activity of ethanol, ethanol-water, ethyl acetate, and n-hexane extracts of Momordica charantia against mcf-7 cells in-vitro. Pharmacon: Jurnal Farmasi Indonesia. 2019;16(2):73-82.
10. Kemenkes RI. Farmakope Herbal Indonesia Edisi II. Jakarta: Kementrian Kesehatan RI. 2017.
11. Arba M, Susilawati Y, Mustarichie R. Hair growth promoting activity of langir bark (Albizia saponaria Lour.) ethanol extract: In-vivoASSAY. Rasayan Journal of Chemistry. 2022;15(3):2065-71.
12. Do QD, Angkawijaya AE, Tran-Nguyen PL, Huynh LH, Soetaredjo FE, Ismadji S, Ju YH. Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of Limnophila aromatica. Journal of Food and Drug Analysis. 2014;22(3):296-302.
13. Azizah DN, Kumolowati E, Faramayuda F. Determination of flavonoid content AlCl3 method in methanol extract of cocoa fruit (Theobroma cacao l.). Kartika Jurnal Ilmiah Farmasi. 2014;2(2):45-9.
14. Gayo Z, Lucida H, Zaini E. Solid dispersion of quercetin-PVP K-30 and its effects on the antioxidant activity. Jurnal Ilmiah Farmasi. 2020;16(2):144-54.
15. Thandapani G, Prasad S, Sudha PN, Sukumaran A. Size optimization and in vitro biocompatibility studies of chitosan nanoparticles. International Journal Of Biological Macromolecules. 2017;104:1794-806.
16. Sivasankarapillai VS , Das SS , Sabir F, Sundaramahalingam MA, Colmenares JC, Prasannakumar S, Rajan M, Rahdar A, Kyzas GZ. Progress in natural polymer engineered biomaterials for transdermal drug delivery systems. Materials Today Chemistry. 2021;19:100382.
17. Moon H, Lertpatipanpong P, Hong Y, Kim CT, Baek SJ. Nano-encapsulated quercetin by soluble soybean polysaccharide/chitosan enhances anticancer, anti-inflammation, and antioxidant activities. Journal of Functional Foods. 2021;87:104756.
18. Suciati T, Nafisa S, Nareswari TL, Juniatik M, Julianti E, Wibowo MS, Yudhistira T, Ihsanawati I, Triyani Y, Khairurrijal K. ArtinM. Grafted phospholipid nanoparticles for enhancing antibiotic cellular uptake against intracellular infection. International Journal of Nanomedicine. 2020;8829-43.
19. Arifin MF, Noviani Y, Nafisa S, Sheilabel A. Preparation, characterization, and optimization of ionic gelated nanoparticles dried extract of temulawak rhizome (Curcuma xanthorrhiza R.) using a factorial design 22. Jurnal Ilmu Kefarmasian Indonesia. 2022;20(2):272-80.
20. Wang X, Luo N, Xu Z, Zheng X, Huang B, Pan X. The estrogenic proliferative effects of two alkylphenols and a preliminary mechanism exploration in MCF‐7 breast cancer cells. Environmental Toxicology. 2020;35(5):628-38.
21. de Oliveira Gonçalves K, Vieira DP, Levy D, Bydlowski SP, Courrol LC. Uptake of silver, gold, and hybrids silver-iron, gold-iron, and silver-gold aminolevulinic acid nanoparticles by MCF-7 breast cancer cells. Photodiagnosis and Photodynamic Therapy. 2020;32:102080.
22. El-Atawy MA, Alsubaie MS, Alazmi ML, Hamed EA, Hanna DH, Ahmed HA, Omar AZ. Synthesis, characterization, and anticancer activity of new N, N′-Diarylthiourea derivative against breast cancer cells. Molecules. 2023;28(17):6420.
23. Utami NF, Sutanto S, Nurdayanty SM, Suhendar U. The effect of various methods of extraction on flavonoid levels flower leaf extract (Plenctranthus scutellariodes). FITOFARMAKA: Jurnal Ilmiah Farmasi. 2020;10(1):76-83.
24. Saini A, Panesar PS, Bera MB. Comparative study on the extraction and quantification of polyphenols from citrus peels using maceration and ultrasonic technique. Current Research in Nutrition & Food Science. 2019;7(3):678-85.
25. Rukmana RM, Sawal AA, Wibawa DA. Combination of antibacterial activity of ethanol extract of meniran leaves and kenikir leaves against Shigella dysenteriae. In1st International Conference for Health Research BRIN ICHR 2022. 2023;7-20.
26. Pakade VE, Lesaoana M, Tavengwa NT. Effect of pH, time and temperature on forced degradation studies of quercetin in presence of polymers. Asian Journal of Chemistry. 2016;28(10):2181-7.
27. Fadillah A, Rahmadani A, Rijai L. Analysis of total flavonoid levels and antioxidant activity test of kelubut leaf extract (Passiflora foetida L.). In Proceeding of Mulawarman Pharmaceuticals Conferences. 2017; 5: 21-8.
28. Jabbari M, Khosravi N, Feizabadi M, Ajloo D. Solubility temperature and solvent dependence and preferential solvation of citrus flavonoid naringin in aqueous DMSO mixtures: an experimental and molecular dynamics simulation study. RSC advances. 2017;7(24):14776-89.
29. Tamayo-Ramos JA, Martel S, Barros R, Bol A, Atilhan M, Aparicio S. On the behavior of quercetin+ organic solvent solutions and their role for C60 fullerene solubilization. Journal of Molecular Liquids. 2022;345:117714.
30. Alshehri S, Shakeel F, Alam P, Pena A, Jouyban A, Martinez F. Effect of temperature and polarity on the solubility and preferential solvation of sinapic acid in aqueous mixtures of DMSO and Carbitol. Journal of Molecular Liquids. 2021;340:117268.
31. Marudova M, Zahariev N, Milenkova S, Pilicheva B, Viraneva A, Yovcheva T. Development and in‐vitro characterization of benzydamine loaded chitosan nanoparticles. In Macromolecular Symposia. 2021;395(1):2000279.
32. Ranjit K, Baquee AA. Nanoparticle: an overview of preparation, characterization, and application. Int Res J Pharm. 2013;4(4):47-57.
33. Verma S, Kumar S, Gokhale R, Burgess DJ. Physical stability of nanosuspensions: Investigation of the role of stabilizers on ostwald ripening. Int J Pharm. 2011; 406(1- 2):45-52.
34. Goel S, Sachdeva M, Agarwal V. Nanosuspension technology: recent patents on drug delivery and their characterizations. Recent pat drug deliv formul. 2019; 13(2): 91–104.
35. Vecchi CF, Cesar GB, Souza PR, Caetano W, Bruschi ML. Mucoadhesive polymeric films comprising polyvinyl alcohol, polyvinylpyrrolidone, and poloxamer 407 for pharmaceutical applications. Pharmaceutical Development and Technology. 2021;26(2):138-49.
36. Bandulasena MV, Goran TV, Omololu GO, Brahim B. Continuous synthesis of PVP stabilized biocompatible gold nanoparticles with a controlled size using a 3D glass capillary microfluidic device. Chem Eng Sci. 2017; 171: 233–43.
37. Lakshmi P, Kumar GA. Nanosuspension technology: a review. Int J Pharm Pharm Sci. 2010;2(4):35-40.
38. Kusuma AW, Aries NN, Hartanti D. Cytotoxic and antiproliferative effects of quercetin on colon cancer cells WiDr. PHARMACY: Jurnal Farmasi Indonesia. 2010; 7(03):107-22
39. Oueslati MA, Gunenc A, Rigane G, Ghazghazi H, Valencia C, SALEM RB, Boukhchina S, Willmore WG, Hosseinian F. Chemical composition, antioxidant and cytotoxic activities of Onopordum acanthium L. crude oil and defatted meal. Rev. Roum. Chim. 2019;64(6):503-10.
40. Fauzia A, Wati UA, Rizkita CG, Qori’ah EW, Arifin I. The effect of marigold leaves and doxorubicin toward cell cycle and apoptosis of T47D cells. Indonesian Journal of Cancer Chemoprevention. 2016;7(3):79-86.
Published
2023-10-27
How to Cite
NAFISA, Safira et al.
Cosmos caudatus Kunth. Leaf Extract Herbal Nanosuspension Formulations, Characterization, and Cytotoxicity Approach Against MCF-7 Breast Cancer Cells.
JURNAL ILMU KEFARMASIAN INDONESIA, [S.l.], v. 21, n. 2, p. 286-294, oct. 2023.
ISSN 2614-6495.
Available at: <http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/1481>. Date accessed: 05 nov. 2024.
doi: https://doi.org/10.35814/jifi.v21i2.1481.
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