Natural polymers for vaginal mucoadhesive delivery of vinegar, using design of experiment methods

  • Shirin Parvinroo Department of Pharmacognosy, Rasht, Iran
  • Maede Eslami Guilan University of Medical Sciences, Faculty of Pharmacy, Department of Pharmaceutics, Rasht, Iran
  • Heshmatollah Ebrahimi-Najafabadi Guilan University of Medical Sciences, Faculty of Pharmacy, Department of Medicinal Chemistry, Rasht, Iran
  • Zahra Hesari Guilan University of Medical Sciences, Faculty of Pharmacy, Department of Pharmacognosy, Department of Pharmaceutics, Rasht, Iran
Keywords: acetic acid;, gels;, polymers; tragacanth;, vaginal creams, foams, jellies;, xanthan gum.

Abstract


Background/Aim. Vinegar is one of the main international traditional nutraceuticals, and it has been used as a vaginal health protectant due to vagina pH balance maintenance and antimicrobial properties. Since the main form of vinegar is liquid, it is difficult to apply vaginally due to its short retention. The aim of this study was to design a vaginal mucoadhesive gel made of vinegar. Methods. Xanthan gum and tragacanth were utilized as natural gel-forming polymers. The effects of xanthan gum and tragacanth on mucoadhesion strength and drug release of the gel formulations were optimized using a 3 level (32) factorial design. Several physico-chemical properties of the gel formulations, including gel viscosity, lubricity, scanning electron microscopy (SEM) images of hydrogel chains, and chain release kinetic, were also investigated. Results. It was found that tragacanth possessed a statistically significant effect on release rate control (p-value = 0.0027), while both tragacanth and xanthan gum had a significant effect (p-value = 0.0001 and 0.0017, respectively) on mucoadhesion property. Formulation F7 with 5% xanthan gum and 1% tragacanth (mucoadhesion = 0.4632 N and release rate = 88.8% in 6 hours) considered as the optimum formulation with some modifications. Conclusion. Xanthan gum and tragacanth can be considered as appropriate natural polymers for vaginal drug delivery.

References

das Neves J, Bahia MF. Gels as vaginal drug delivery systems. Int J Pharm 2006; 318(1‒2): 1‒14.

Sarwal A, Singh G, Singh S, Singh K, Sinha V. Novel and effec-tual delivery of an antifungal agent for the treatment of persis-tent vulvovaginal candidiasis. J Pharm Investig 2018; 49(4): 135‒47.

Andrade AO, Parente ME, Ares G. Screening of mucoadhesive vaginal gel formulations. Braz Jf Pharm Sci 2014; 50(4): 931‒41.

Boris S, Barbés C. Role played by lactobacilli in controlling the population of vaginal pathogens. Microbes Infect 2000; 2(5): 543‒6.

Conti C, Malacrino C, Mastromarino P. Inhibition of herpes sim-plex virus type 2 by vaginal lactobacilli. J Physiol Pharmacol 2009; 60(Suppl 6): 19‒26.

Graver MA, Wade JJ. The role of acidification in the inhibition of Neisseria gonorrhoeae by vaginal lactobacilli during anaero-bic growth. Ann Clin Microbiol Antimicrob 2011; 10: 8.

Juárez Tomás MS, Ocaña VS, Wiese B, Nader-Macías ME. Growth and lactic acid production by vaginal Lactobacillus acidophilus CRL 1259, and inhibition of uropathogenic Esch-erichia coli. J Med Microbiol 2003; 52(Pt 12): 1117‒24.

Shukair SA, Allen SA, Cianci GC, Stieh DJ, Anderson MR, Baig SM, et al. Human cervicovaginal mucus contains an activity that hinders HIV-1 movement. Mucosal Immunol 2013; 6(2): 427‒34.

Lai SK, Hida K, Shukair S, Wang YY, Figueiredo A, Cone R, et al. Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. J Virol 2009; 83(21): 11196‒200.

Das P, Swain T, Mohanty JR, Sinha S, Padhi B, Torondel B, et al. Higher vaginal pH in Trichomonas vaginalis infection with in-termediate Nugent score in reproductive-age women-a hospi-tal-based cross-sectional study in Odisha, India. Parasitol Res 2018; 117(9): 2735‒42.

Brotman RM, Bradford LL, Conrad M, Gajer P, Ault K, Peralta L, et al. Association between Trichomonas vaginalis and vagi-nal bacterial community composition among reproductive-age women. Sex Transm Dis 2012; 39(10): 807‒12.

Patel P, Patel P. Formulation and evaluation of clindamycin HCL in situ gel for vaginal application. Int J Pharm Investig 2015; 5(1): 50‒6.

Rencber S, Karavana SY, Şenyiğit ZA, Erac B, Limoncu MH, Baloğlu E. Mucoadhesive in situ gel formulation for vaginal de-livery of clotrimazole: formulation, preparation, and in vitro/in vivo evaluation. Pharm Dev Technol 2017; 22(4): 551‒61.

de Araujo Pereira RR, Bruschi ML. Vaginal mucoadhesive drug delivery systems. Drug Dev Ind Pharm 2012; 38(6): 643‒52.

Khan M, Shah LA, Rehman T, Khan A, Iqbal A, Ullah M, et al. Synthesis of physically cross-linked gum Arabic-based polymer hydrogels with enhanced mechanical, load bearing and shape memory behavior. Iran Polym J 2020; 29(4): 1‒10.

Bonferoni MC, Giunchedi P, Scalia S, Rossi S, Sandri G, Caramella C. Chitosan gels for the vaginal delivery of lactic acid: rele-vance of formulation parameters to mucoadhesion and release mechanisms. AAPS PharmSciTech 2006; 7(4): 104.

Ramadan AA, Elbakry AM, Esmaeil AH, Khaleel SA. Pharma-ceutical and pharmacokinetic evaluation of novel rectal mu-coadhesive hydrogels containing tolmetin sodium. J Pharm In-vestig 2018; 48(6): 673‒83.

Braunstein S, van de Wijgert J. Preferences and practices related to vaginal lubrication: implications for microbicide acceptabil-ity and clinical testing. J Womens Health (Larchmt) 2005; 14(5): 424‒33.

Vandebosch A, Goetghebeur E, Ramjee G, Alary M, Ettiègne-Traoré V, Chandeying V, et al. COL-1492 Study Group. Ac-ceptability of COL-1492, a vaginal gel, among sex workers in one Asian and three African cities. Sex Transm Infect 2004; 80(3): 241‒3.

Wadhera P, Jindal R, Dogra R. Insight into adsorption kinetics and isotherms for adsorption of methylene blue using gum ros-in alcohol/psyllium-based green adsorbent. Iran Polym J 2020; 29: 501‒14.

Şenyiğit ZA, Karavana SY, Eraç B, Gürsel Ö, Limoncu MH, Baloğlu E. Evaluation of chitosan based vaginal bioadhesive gel formulations for antifungal drugs. Acta Pharmaceutica 2014; 64(2): 139‒56.

Malik NS, Ahmad M, Minhas MU, Tulain R, Barkat K, Khalid I et al. Chitosan/Xanthan Gum Based Hydrogels as Potential Carrier for an Antiviral Drug: Fabrication, Characterization, and Safety Evaluation. Front Chem 2020; 8: 50.

Apoorva A, Rameshbabu AP, Dasgupta S, Dhara S, Padmavati M. Novel pH-sensitive alginate hydrogel delivery system rein-forced with gum tragacanth for intestinal targeting of nutraceuticals. Int J Biol Macromol 2020; 147: 675‒87.

Selig MJ, Gamaleldin S, Celli GB, Marchuk MA, Smilgies DM, Abbaspourrad A. The stabilization of food grade copper-chlorophyllin in low pH solutions through association with an-ionic polysaccharides. Food Hydrocoll 2020; 98: 105255.

Farzi M, Emam-Djomeh Z, Mohammadifar MA. A comparative study on the emulsifying properties of various species of gum tragacanth. Int J Biol Macromol 2013; 57: 76‒82.

Cazorla-Luna R, Notario-Pérez F, Martín-Illana A, Bedoya Lm, Tamayo A, Rubio J, et al. Development and in vitro/ex vivo characterization of vaginal mucoadhesive bilayer films based on ethylcellulose and biopolymers for vaginal sustained release of Tenofovir. Biomacromolecules 2020; 21(6): 2309‒19.

Ghosal K, Adak S, Agatemor C, Praveen G, Kalarikkal N, Thomas S. Novel interpenetrating polymeric network based mi-crobeads for delivery of poorly water soluble drug. J Polym Res 2020; 27(4): 1‒11.

Ugoeze KC. Bioadhesive Polymers for Drug Delivery Applica-tions. In: Mittal KL, Bakshi IS, Narang JK, editors. Bioad-hesives in Drug Delivery. Hoboken, New Jersey; Wiley; 2020. p. 29‒56.

Aghili Khorasani M. Makhzan al-Advie. Teheran: Iran Universi-ty of Medical Science, Research Institute for Islamic and Complementary Medicine; 2009.

Samad A, Azlan A, Ismail A. Therapeutic effects of vinegar: A review. Food Sci 2016; 8: 56‒61.

Tonekaboni M. Tohfat al Momenin. Tehran: Nashre Shahr; 2008.

Heydari M, Dalfardi B, Golzari SE, Habibi H, Zarshenas MM. The medieval origins of the concept of hypertension. Heart Views 2014; 15(3): 96‒8.

Tansaz M, Meyari A, Naeemi SA, Meybodi RN, Memarzade H, Shirooye P, et al. Recommended treatment methods of Iranian traditional medicine for female genital tract infections. Avi-cenna J Phytomed 2015; 5: 88‒9.

Johnston CS, Gaas CA. Vinegar: medicinal uses and antiglyce-mic effect. MedGenMed 2006; 8(2): 61.

Pavlova SI, Tao L. In vitro inhibition of commercial douche products against vaginal microflora. Infect Dis Obstet Gyne-col 2000; 8(2): 99‒104.

Martino JL, Vermund SH. Vaginal douching: evidence for risks or benefits to women’s health. Epidemiol Rev 2002; 24(2): 109‒24.

Ho CW, Lazim AM, Fazry S, Zaki UKHH, Lim SJ. Varieties, production, composition and health benefits of vinegars: A review. Food Chem 2017; 221: 1621‒30.

Ebrahimi-Najafabadi H, Leardi R, Jalali-Heravi M. Experi-mental design in analytical chemistry - part I: theory. J AOAC Int 2014; 97(1): 3‒11.

Ebrahimi-Najafabadi H, Pasdaran A, Rezaei Bezenjani R, Bo-zorgzadeh E. Determination of toxic heavy metals in rice sam-ples using ultrasound assisted emulsification microextraction combined with inductively coupled plasma optical emission spectroscopy. Food Chem 2019; 289: 26‒32.

Montgomery DC. Design and Analysis of Experiments. 5th ed. Chichester, UK: John Wiley & Sons; 2001. p. 363–73.

Soares PA, de Seixas JR, Albuquerque PB, Santos GR, Mourão PA, Barros W Jr, et al. Development and characterization of a new hydrogel based on galactomannan and κ-carrageenan. Carbohydr Polym 2015; 134: 673‒9.

Dantas MG, Reis SA, Damasceno CM, Rolim LA, Rolim-Neto PJ, Carvalho FO, et al. Development and Evaluation of Stability of a Gel Formulation Containing the Monoterpene Borneol. ScientificWorldJournal 2016; 2016: 7394685.

Deuschle VCKN, Deuschle RAN, Bortoluzzi MR, Athayde ML. Physical chemistry evaluation of stability, spreadability, in vitro antioxidant, and photo-protective capacities of topical formulations containing Calendula officinalis L. leaf extract. Braz J Pharm Sci 2015; 51(1): 63‒75.

Tasdighi E, Jafari Azar Z, Mortazavi SA. Development and In-vitro Evaluation of a Contraceptive Vagino-Adhesive Pro-pranolol Hydrochloride Gel. Iran J Pharm Res 2012; 11(1): 13‒26.

Nie S, Hsiao WL, Pan W, Yang Z. Thermoreversible Pluronic F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies. Int J Nanomedicine 2011; 6: 151‒66.

Rasul A, Iqbal M, Murtaza G, Waqas MK, Hanif M, Khan SA, et al. Design, development and in-vitro evaluation of metoprolol tartrate tablets containing xanthan-tragacanth. Ac-ta Pol Pharm 2010; 67(5): 517‒22.

Salamanca CH, Yarce CJ, Moreno RA, Prieto V, Recalde J. Natu-ral gum-type biopolymers as potential modified nonpolar drug release systems. Carbohydr Polym 2018; 189: 31‒8.

Pocan P, Ilhan E, Oztop MH. Characterization of Emulsion Sta-bilization Properties of Gum Tragacanth, Xanthan Gum and Sucrose Monopalmitate: A Comparative Study. J Food Sci 2019; 84(5): 1087‒93.

Published
2022/05/20
Section
Original Paper