Intravaginal delivery of reverse micellar epigallocatechin loaded in ĸ-carrageenan and HPMC K100M-based gel
Abstract
A gel with mucoadhesive properties and a controlled release profile is a suitable dosage form for reverse
micellar EGCG delivery. In this study, ĸ-Carrageenan and HPMC K100M were used as the gel components at a weight
ratio of 1:1.5, respectively, for loading native and reverse micellar EGCG. The characteristics of the gel were determined
based on pH, swelling index, disintegration time, hardness, and entrapment efficiency. The in vitro EGCG release rate
was further determined for EGCG levels. Moreover, in vivo cervical penetration studies of rhodamine-labeled EGCG
gels in mice at two and six hours after intravaginal administrations were conducted. The results showed that the pH
and hardness characteristics of the gels for each formula did not differ significantly, while the gel-loaded reverse
micellar EGCG had a higher swelling index than that of native EGCG gels. In addition, the rate of release and cervical
penetration of rhodamine-labeled reverse micellar EGCG loaded in gels was higher than those of rhodamine-labeled
native EGCG gels. Therefore, it can be concluded that loading reverse micelles EGCG into gels prepared with ĸ-
Carrageenan and HPMC K100M successfully controlled the release rate and improved cervical penetration, thereby
enabling its potential use in cervical cancer treatment.
Keywords
Epigallocatechin gallate cancer hydroxypropyl methylcellulose κ-carrageenan reverse micelle cervical penetration
References
- 1. World Health Organization (WHO). Cervical Cancer. https://www.who.int/cancer/prevention/diagnosisscreening/ cervical-cancer/en/(accessed on 14 January 2017)
- 2. Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality ofcervical cancer in 2018: a worldwide analysis. Lancet Glob Heal. 2020;8(2):e191–203. [CrossRef]
- 3. Li K, Yin R, Wang D, Li Q. Human papillomavirus subtypes distribution among 2309 cervical cancer patients in West China. Oncotarget. 2017;8(17):28502–9. [CrossRef]
- 4. Kashyap N, Krishnan N, Kaur S, Ghai S. Risk Factors of Cervical Cancer: A Case-Control Study. Asia-Pacific JOncol Nurs. 2019;6(3):308–14. [CrossRef]
- 5. Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynecol Obstet. 2018;143:22– 36.[CrossRef]
- 6. Nurgali K, Jagoe RT, Abalo R. Editorial: Adverse effects of cancer chemotherapy: Anything new to improvetolerance and reduce sequelae? Front Pharmacol. 2018;9(MAR):1–3. [CrossRef]
- 7. Du GJ, Wang CZ, Qi LW, Zhang ZY, Calway T, He TC, et al. The synergistic apoptotic interaction of panaxadiol and epigallocatechin gallate in human colorectal cancer cells. Phyther Res. 2013;27(2):272–7. [CrossRef]
- 8. Almatroodi SA, Almatroudi A, Khan AA, Alhumaydhi FA, Alsahli MA, Rahmani AH. Potential therapeutic targets of epigallocatechin gallate (egcg), the most abundant catechin in green tea, and ıts role in the therapy ofvarious types of cancer. Molecules. 2020 Jul 9;25(14):3146. [CrossRef]
- 9. Sharma C, Nusri QEA, Begum S, Javed E, Rizvi TA, Hussain A. (-)-Epigallocatechin-3-gallate induces apoptosis and inhibits invasion and migration of human cervical cancer cells. Asian Pacific J Cancer Prev. 2012;13(9):4815–22.[CrossRef]
- 10. Yoshino S, Mitoma T, Tsuruta K, Todo H, Sugibayashi K. Effect of emulsification on the skin permeation and UV protection of catechin. Pharm Dev Technol. 2014;19(4):395–400.[CrossRef]
- 11. Gan RY, Li H Bin, Sui ZQ, Corke H. Absorption, metabolism, anticancer effect and molecular targets ofepigallocatechin gallate (EGCG): An updated review. Crit Rev Food Sci Nutr. 2018;58(6):924–41.[CrossRef]
- 12. Rosita N, Nailufa Y, Hariyadi DM. Characteristics, stability and activity of epigallocatechin gallate (EGCG)-chitosan microspheres: Effect of polymer concentration. Res J Pharm Technol. 2020;13(5):2303–9. [CrossRef]
- 13. Diamant H, Andelman D. Onset of self-assembly in polymer-surfactant systems. Europhys Lett. 1999;48(2):170–6.[CrossRef]
- 14. Loyd V.Allen J, Ansel HC. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. 10th ed. Lippincott Williams & Wilkins, Philadelphia, PA 2014.
- 15. De Araújo Pereira RR, Bruschi ML. Vaginal mucoadhesive drug delivery systems. Drug Dev Ind Pharm. 2012;38(6):643–52.[CrossRef]
- 16. Acarturk F. Mucoadhesive Vaginal Drug Delivery Systems. Recent Pat Drug Deliv Formul. 2009;3(3):193–205. [CrossRef]
- 17. Rowe RC, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical Excipients. 6th ed. USA: RPS Publishing; 2009.
- 18. Pacheco-Quito EM, Ruiz-Caro R, Rubio J, Tamayo A, Veiga MD. Carrageenan-based acyclovir mucoadhesivevaginal tablets for prevention of genital herpes. Mar Drugs. 2020;18(5). [CrossRef]
- 19. Perioli L, Ambrogi V, Pagano C, Massetti E, Rossi C. New solid mucoadhesive systems for benzydamine vaginal administration. Colloids Surfaces B Biointerfaces. 2011;84(2):413–20. [CrossRef]
- 20. Necas J, Bartosikova L. Carrageenan: a review. Vet Med (Praha). 2013;58(4):187–205. [CrossRef].
- 21. Sánchez-Sánchez M. P., Martín-Illana A., Ruiz-Caro R., Bermejo P., Abad M. J., Carro R., Bedoya L. M., Tamayo A., Rubio J., Fernández-Ferreiro A., Otero-Espinar F., & Veiga M. D. Chitosan and kappa-carrageenan vaginal acyclovir formulations for prevention of genital herpes. ın vitro and ex vivo evaluation. Mar Drugs. 2015;13(9):5976–92. [CrossRef]
- 22. Son GH, Lee BJ, Cho CW. Mechanisms of drug release from advanced drug formulations such as polymeric-based drug-delivery systems and lipid nanoparticles. J Pharm Investig. 2017;47(4):287–96.[CrossRef]
- 23. Miatmoko A, Ayunin Q, Soeratri W. Ultradeformable vesicles: concepts and applications relating to the delivery of skin cosmetics. Ther Deliv. 2021;12:739–56.[CrossRef]
- 24. Rosita N, Meitasari VA, Rianti MC, Hariyadi DM. Enhancing skin penetration of epigallocatechin gallate by modifying partition coefficient using reverse micelle method. Ther Deliv. 2019;10(7):409–17. [CrossRef]
- 25. Benson HAE. Topical and Transdermal Drug Delivery. In: Topical and Transdermal Drug Delivery. A John Wiley & Sons, Inc., Publication; 2005. p. 5–37.[CrossRef]
- 26. Mohsenipour AA, Pal R. A Review of Polymer-Surfactant Interactions. In: Handbook of Surface and Colloid Chemistry. 4th ed. U.S.: CRC Press; 2016. p. 639. [CrossRef]
- 27. Owen SC, Doak AK, Wassam P, Shoichet MS, Shoichet BK. Colloidal aggregation affects the efficacy of anticancerdrugs in cell culture. ACS Chem Biol. 2012;7(8):1429–35. [CrossRef]
- 28. Alvarez-Lorenzo C, Concheiro A. Effects of surfactants on gel behavior : design ımplications for drug delivery effects of surfactants on gel behavior design ımplications for drug delivery systems. Am J Drug Deliv. 2003;1(2):77– 101. [CrossRef]
- 29. Sardar N, Kamil M, Kabir-Ud-Din. Interaction between non-ionic polymer hydroxypropyl methyl cellulose(HPMC) and cationic gemini/conventional surfactants. Ind Eng Chem Res. 2012;51(3):1227–35.[CrossRef]
- 30. Bao H, Li N, Gan LH, Zhang H. Interactions between ionic surfactants and polysaccharides in aqueous solutions. Macromolecules. 2008;41(23):9406–12. [CrossRef]
- 31. dos Santos MA, Grenha A. Polysaccharide nanoparticles for protein and peptide delivery: exploring less-known materials. 1st ed. Vol. 98, Advances in protein chemistry and structural biology. Elsevier Inc.; 2015. 223–261 p. [CrossRef]
- 32. Yoo J, Won Y. Phenomenology of the Initial Burst Release of Drugs from PLGA Microparticles. ACS Biomater Sci Eng. 2020;6:6053–62. [CrossRef]
- 33. Paul DR. Elaborations on the Higuchi model for drug delivery. Int J Pharm. 2011;418(1):13–7. [CrossRef]
- 34. Bruschi ML. 5 - Mathematical models of drug release. In: Bruschi MLBT-S to M the DR from PS, editor. Strategiesto Modify the Drug Release from Pharmaceutical Systems. Woodhead Publishing; 2015. p. 63–86.
- 35. Yadav G, Bansal M, Thakur N, Khare P. Multilayer tablets and their drug release kinetic models for oral controlled drug delivery system. Middle-East J Sci Res. 2013;16(6):782–95.
- 36. Liechty WB, Kryscio DR, Slaughter B V, Peppas NA. Polymers for drug delivery systems. Annu Rev Chem Biomol Eng. 2010;1:149–73. [CrossRef]
- 37. Mazyed EA, Helal DA, Elkhoudary MM, Abd Elhameed AG, Yasser M. Formulation and optimization of nanospanlastics for ımproving the bioavailability of green tea epigallocatechin gallate. Pharmaceuticals. 2021 Jan 15;14(1):68. . [CrossRef]
- 38. Gomaa E, Abu Lila AS, Hasan AA, Ghazy F eldin S. Preparation and characterization of intravaginal vardenafil suppositories targeting a complementary treatment to boost in vitro fertilization process. Eur J Pharm Sci. 2018;111:113–20. [CrossRef]
- 39. Reddy RS, Kumar L, Pydi CR, Reddy MS, Verma R. Development of Fluconazole Suppositories for the Treatment of Candida Infection of Genitourinary Tract. Indian J Pharm Educ Res. 2018;52(4):S16-22.
- 40. Mohamed DFM, Mahmoud OAE, Mohamed FA. Preparation and Evaluation of Ketotifen Suppositories. J Adv Biomed Pharm Sci. 2020;3:10–22.
- 41. Hassan AS, Soliman GM, Ali MF, El-Mahdy MM, El-Gindy GEDA. Mucoadhesive tablets for the vaginal delivery of progesterone: in vitro evaluation and pharmacokinetics/pharmacodynamics in female rabbits. Vol. 44, Drug Development and Industrial Pharmacy. Taylor & Francis; 2018. 224–232 p.[CrossRef]
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmaceutical Sciences |
| Journal Section | Articles |
| Authors | |
| Publication Date | June 28, 2025 |
| Published in Issue | Year 2022 Volume: 26 Issue: 4 |