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Pharmaceutics. 2020 Apr 11;12(4). doi: 10.3390/pharmaceutics12040346.

Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells.

Pharmaceutics

Nabil A Alhakamy, Usama A Fahmy, Shaimaa M Badr-Eldin, Osama A A Ahmed, Hani Z Asfour, Hibah M Aldawsari, Mardi M Algandaby, Basma G Eid, Ashraf B Abdel-Naim, Zuhier A Awan, Nabil K Alruwaili, Amir I Mohamed

Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  2. Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  3. King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  4. Advanced drug delivery research group, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  5. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
  6. Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  7. Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21579, Saudi Arabia.
  8. Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
  9. Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  10. Department of Pharmaceutics, Faculty of Pharmacy, Jouf University, Skaka 2014, Saudi Arabia.
  11. Department of Pharmaceutics and Industrial Pharmacy, Military Medical Academy, Cairo 11757, Egypt.

PMID: 32290412 PMCID: PMC7238269 DOI: 10.3390/pharmaceutics12040346

Abstract

Icariin (ICA) is a flavonol glycoside that has pleiotropic pharmacological actions. It has cytotoxic effects against ovarian cancer cells and increases their chemosensitivity to chemotherapeutic drugs. Phytosomes are identified for their potential in drug delivery of cytotoxic agents. Thus, the purpose of this study was to determine the potential enhancement of ICA cytotoxicity activity in OVCAR-3 ovarian cancer cells via its formulation in phytosomes. ICA-phytosomal formulation was optimized using a Box-Behnken design. Particle size, shape, and in vitro drug release were used to characterize the optimized formula. The optimized formulation exhibited enhanced in vitro drug release. ICA-phytosomes exhibited enhanced cytotoxicity against ovarian cancer cells. Cell cycle analysis indicated accumulation of cells challenged with ICA-phytosomes in G2/M and pre-G1 phases. Staining of cells with annexin V indicated significant elevation of percentage cells with early and late apoptosis as well as total cell death. In addition, the formulation significantly disturbed mitochondrial membrane potential and cellular content of caspase 3. In addition, intracellular release of reactive oxygen species (ROS) was enhanced by ICA-phytosomes. In conclusion, phytosome formulation of ICA significantly potentiates its cytotoxic activities against OVCAR-3 cells. This is mediated, at least partly, by enhanced ICA cellular permeation, apoptosis, and ROS.

Keywords: apoptosis; caspase; icariin; phytosomes; reactive oxygen species

References

  1. Pharm Dev Technol. 2020 Apr;25(4):397-407 - PubMed
  2. Indian J Cancer. 2014 Mar;51 Suppl 3:e72-6 - PubMed
  3. Apoptosis. 2015 Sep;20(9):1229-41 - PubMed
  4. Oncol Rep. 2015 Jun;33(6):2829-36 - PubMed
  5. Biomed Pharmacother. 2018 Mar;99:128-133 - PubMed
  6. Surg Clin North Am. 2008 Apr;88(2):285-99, vi - PubMed
  7. J Biomed Nanotechnol. 2016 Sep;12(9):1746-57 - PubMed
  8. Exp Ther Med. 2014 May;7(5):1116-1122 - PubMed
  9. J Natl Cancer Inst. 2000 Jul 5;92(13):1042-53 - PubMed
  10. 3 Biotech. 2020 Mar;10(3):133 - PubMed
  11. J Exp Clin Cancer Res. 2018 Nov 1;37(1):266 - PubMed
  12. Int J Nanomedicine. 2014 Jun 12;9:2891-903 - PubMed
  13. AAPS J. 2016 Jan;18(1):102-14 - PubMed
  14. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):801-811 - PubMed
  15. Eur J Pharm Sci. 2009 Mar 2;36(4-5):580-90 - PubMed
  16. Brain Dev. 2017 Aug;39(7):593-600 - PubMed
  17. Front Pharmacol. 2017 Oct 12;8:734 - PubMed
  18. J Sex Med. 2007 Nov;4(6):1582-92 - PubMed
  19. Methods Mol Biol. 2016;1473:17-22 - PubMed
  20. Int J Mol Sci. 2019 Nov 18;20(22): - PubMed
  21. Int J Pharm. 2019 Oct 30;570:118657 - PubMed
  22. Eur J Pharmacol. 2019 Jan 5;842:20-32 - PubMed
  23. J Drug Target. 2008 Feb;16(2):108-23 - PubMed
  24. Int Immunopharmacol. 2015 Dec;29(2):401-407 - PubMed
  25. J Agric Food Chem. 2011 Sep 14;59(17):9280-9 - PubMed
  26. Int J Oncol. 2019 Jun;54(6):1933-1942 - PubMed
  27. Int J Pharm. 2010 Aug 16;395(1-2):272-80 - PubMed
  28. Br J Pharmacol. 2010 Feb;159(4):939-49 - PubMed
  29. Adv Pharmacol. 2020;87:179-203 - PubMed
  30. Front Pharmacol. 2017 Feb 14;8:51 - PubMed
  31. Cancer Lett. 2010 Dec 8;298(2):222-30 - PubMed
  32. Beilstein J Nanotechnol. 2019 Sep 24;10:1933-1942 - PubMed
  33. Molecules. 2016 Mar 02;21(3):297 - PubMed
  34. Mol Med Rep. 2019 Oct;20(4):3433-3439 - PubMed
  35. Pharmacol Rep. 2017 Aug;69(4):616-624 - PubMed
  36. J Microencapsul. 2002 Jul-Aug;19(4):451-61 - PubMed
  37. J Control Release. 2007 Nov 6;123(2):148-54 - PubMed
  38. Front Pharmacol. 2019 Mar 19;10:271 - PubMed
  39. Adv Pharm Bull. 2017 Apr;7(1):35-42 - PubMed
  40. Int J Pharm. 2014 Aug 25;471(1-2):173-81 - PubMed
  41. Sci Rep. 2016 Jun 08;6:27669 - PubMed
  42. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):747-756 - PubMed
  43. Methods Mol Biol. 2019;1894:123-131 - PubMed
  44. Front Chem. 2018 Aug 20;6:360 - PubMed
  45. Int J Pharm. 2016 Feb 10;498(1-2):283-93 - PubMed
  46. AAPS PharmSciTech. 2016 Jun;17(3):607-17 - PubMed
  47. Int J Pharm. 2018 Jan 15;535(1-2):18-26 - PubMed
  48. Front Pharmacol. 2016 Jun 29;7:191 - PubMed
  49. Front Pharmacol. 2018 May 30;9:531 - PubMed
  50. Molecules. 2019 Jun 29;24(13): - PubMed
  51. Asian J Pharm Sci. 2019 May;14(3):265-274 - PubMed
  52. J Appl Toxicol. 2018 May;38(5):616-627 - PubMed

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