Abstract
Mentha longifolia L. is used in folk medicine and its essential oil has antimicrobial and aromatic properties. The present invention relates to the development of hydrogel formulation of Mentha longifolia essential oil (EOML) for treating oral candidiasis. Various EOML hydrogels were developed using mucoadhesive polymers viz., Carbopol 940, sodium carboxymethylcellulose and their blends. The hydrogels were characterized with respect to physical, rheological and textural attributes. Finally, all the EOML based hydrogels were evaluated for in vitro efficacy against Candida albicans employing agar well diffusion and broth dilution assay. The EOML hydrogels were semisolid, off-white color, non-gritty, most stable at 4 and 25 °C, and possessed optimum spreading and pleasing aesthetic attributes. The hydrogels showed pseudo-plastic shear-thinning behaviour and variable viscosity, dependent on the concentration and type of gelling agent. The single polymer-based formulations (F1 and F2) were able to spread better compared to blended polymer formulations (F5 and F6). In broth dilution assay, of all the prepared mucoadhesive hydrogels, F1 (containing 5% Carbopol 940) exhibited lowest MIC value against Candida albicans (ATCC90028 and MTCC277), vis-a-vis EOML and standard drugs (i.e., Amphotericin B and Fluconazole). Further, there was marked enhancement in the antifungal efficacy of F1 in comparison to EOML (20 folds), Amphotericin B (2 folds) and Fluconazole (2 folds). Thus, the hydrogel formulation ensured reduced volatility of EOML and improved its therapeutic effectiveness. Owing to the mucoadhesive components and non-toxic properties of the EOML hydrogel, the formulation can be extended for clinical evaluation for treating oral thrush.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
The authors confirm that the data supporting the findings of this study are available within the article.
Abbreviations
- EOML:
-
Essential oil of Mentha longifolia
- TEA:
-
Triethanolamine
- PEG400:
-
Polyethylene glycol 400
- DMSO:
-
Dimethyl sulfoxide
- NaCMC:
-
Sodium carboxymethylcellulose
- YPD:
-
Yeast extract peptone dextrose
- F1:
-
Formulation 1
- F2:
-
Formulation 2
- F3:
-
Formulation 3
- F4:
-
Formulation 4
- F5:
-
Formulation 5
- AMPB:
-
Amphotericin B
- SS:
-
Semisolid
- SL:
-
Slightly liquid
- OW:
-
Off-white
- CH:
-
Characteristic
- US:
-
Unpleasant smell
- NSL:
-
No separation of layer
- FLU:
-
Fluconazole
- MIC:
-
Minimum inhibitory concentration
References
Adwan G, Salameh Y, Adwan K et al (2012) Assessment of antifungal activity of herbal and conventional toothpastes against clinical isolates of Candida albicans. Asian Pac J Trop Biomed 2:375–379. https://doi.org/10.1016/S2221-1691(12)60059-8
Amir LH, Pakula S (1991) Nipple pain, mastalgia and candidiasis in the lactating breast. Aust N Z J Obstet Gynaecol 31:378–380. https://doi.org/10.1111/j.1479-828X.1991.tb02829.x
Aslani A, Ghannadi A, Najafi H (2013) Design, formulation and evaluation of a mucoadhesive gel from Quercus brantii L. and Coriandrum sativum L. as periodontal drug delivery. Adv Biomed Res 2:21. https://doi.org/10.4103/2277-9175.108007
Bhattarai NK (1992) Medical ethnobotany in the Karnali Zone. Nepal Econ Bot 46:257–261. https://doi.org/10.1007/bf02866624
Bhinge SD, Bhutkar MA, Randive DS et al (2017) Formulation development and evaluation of antimicrobial polyherbal gel. Ann Pharm Fr Elsevier Masson 75:349–358. https://doi.org/10.1016/j.pharma.2017.04.006
Bisht G, Srivastava S, Kulshreshtha R et al (2020) Applications of red pigments from psychrophilic Rhodonellum psychrophilum GL8 in health, food and antimicrobial finishes on textiles. Process Biochemistry 94:15–29. https://doi.org/10.1016/j.procbio.2020.03.021
Chen Y, Cui G, Dan N et al (2019) Preparation and characterization of dopamine–sodium carboxymethyl cellulose hydrogel. SN Appli Sci 1:609. https://doi.org/10.1007/s42452-019-0605-2
Clevenger J (1928) Apparatus for the determination of volatile oil. J Am Pharm Assoc 17:345–9
da Silva RA, Ishikiriama BL, Ribeiro Lopes MM et al (2020) Antifungal activity of Punicalagin–nystatin combinations against Candida albicans. Oral Diseases 26:1810–9. https://doi.org/10.1111/odi.13507
Farzaei MH, Bahramsoltani R, Ghobadi A et al (2017) Pharmacological activity of Mentha longifolia and its phytoconstituents. J Tradit Chin Med 37:710–20. https://doi.org/10.1016/S0254-6272(17)30327-8
Garg A, Aggarwal D, Garg S et al (2002) Spreading of semisolid formulations: an update. Pharm Technol N Am 26:84–105
Ghorpade V, Mali K, Dias R et al (2012) Carbopol and sodium carboxymethylcellulose based methylsulfonylmethane gels for treatment of osteoarthritis: In-vitro and In-vivo Evaluation. Ind J Pharm Educ Res 46:235
Husaini MA (2010) Medicinal and aromatic plant sciences and biotechnology. Global Science Books, Japan
Jalilzadeh-Amin G, Maham M (2015) Antidiarrheal activity and acute oral toxicity of Mentha longifolia L. essential oil. Avicenna J Phytomed 5:128
Khan M, Kumar S, Hamal IA (2009) Medicinal plants of Sewa River catchment area in the northwest Himalaya and its implication for conservation. Ethnobot. Leafl 13:1113–1139
Kumar A, Dev K, Sourirajan A (2021) Essential Oils of Rosmarinus officinalis L., Cymbopogon citratus (DC.) Stapf., and the phyto-compounds, delta-carene and alpha-pinene mediate cell cycle arrest at G2/M transition in budding yeast Saccharomyces cerevisiae. S Afr J Bot 141:296–305. https://doi.org/10.1016/j.sajb.2021.05.008
Mehra A, Bajpai O, Joshi H (2014) Diversity, utilization and sacred values of ethno-medicinal plants of Kumaun Himalaya. Trop Plant Res 1:80–86
Mikaili P, Mojaverrostami S, Moloudizargari M et al (2013) Pharmacological and therapeutic effects of Mentha longifolia L. and its main constituent, menthol. Anc Sci Life 33:131. https://doi.org/10.4103/0257-7941.139059
Mouftah S, Abdel-Mottaleb MM, Lamprecht A (2016) Buccal delivery of low molecular weight heparin by cationic polymethacrylate nanoparticles. Int J Pharm 515:565–74. https://doi.org/10.1016/j.ijpharm.2016.10.039
Negi P, Aggarwal M, Sharma G et al (2017) Niosome-based hydrogel of resveratrol for topical applications: an effective therapy for pain related disorder(s). Biomed Pharmacother 88:480–7. https://doi.org/10.1016/j.biopha.2017.01.083
Negi P, Singh B, Sharma G et al (2016) Phospholipid microemulsion-based hydrogel for enhanced topical delivery of lidocaine and prilocaine: QbD-based development and evaluation. Drug Deliv 23:941–57. https://doi.org/10.3109/10717544.2014.923067
Nidhi P, Kumari R, Thakur S et al (2018a) Role of Essential oils of medicinal plants (Eucalyptus globulus, Thuja occidentalis, Rosmarinus officinalis, Lavandula officinalis) to treat broad spectrum bacterial and fungal pathogens and as antioxidants in food and health. Available at SSRN 3299291. https://doi.org/10.2139/ssrn.3299291
Nidhi P, Rolta R, Kumar V et al (2018b) Phytocompounds from essential oil of Mentha longifolia as synergistic, broad spectrum drug candidates for candidiasis. Indian Patent Filing Number: 201811035174.
Nidhi P, Rolta R, Kumar V et al (2020) Synergistic potential of Citrus aurantium L. essential oil with antibiotics against Candida albicans. J Ethnopharmacol 262:113135. https://doi.org/10.1016/j.jep.2020.113135
Ning M, Guo Y, Pan H et al (2005) Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery systems for clotrimazole. Drug Dev Ind Pharm 31:375–83. https://doi.org/10.1081/DDC-54315
Patil NS, Deshmukh GB, Patil SV (2014) Synthesis and biological evaluation of novel N-aryl maleimide derivatives clubbed with α-hydroxyphosphonates. Eur J Med Chem 83:490–7. https://doi.org/10.1016/j.ejmech.2014.06.053
Pereira CA, da Costa AC, Machado AK et al (2011) Enzymatic activity, sensitivity to antifungal drugs and Baccharis dracunculifolia essential oil by Candida strains isolated from the oral cavities of breastfeeding infants and in their mothers’ mouths and nipples. Mycopathologia 171:103–9. https://doi.org/10.1007/s11046-010-9353-y
Perlroth J, Choi B, Spellberg B (2007) Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol 45:321–46. https://doi.org/10.1080/13693780701218689
Pietrella D, Angiolella L, Vavala E et al (2011) Beneficial effect of Mentha suaveolens essential oil in the treatment of vaginal candidiasis assessed by real-time monitoring of infection. BMC Complement Altern Med 11:18. https://doi.org/10.1186/1472-6882-11-18
Rençber S, Karavana SY, Yilmaz FF et al (2019) Formulation and evaluation of fluconazole loaded oral strips for local treatment of oral candidiasis. J Drug Deliv Sci Technol 49:615–21. https://doi.org/10.1016/j.jddst.2018.12.035
Roque L, Duarte N, Bronze MR et al (2018) Development of a bioadhesive nanoformulation with Glycyrrhiza glabra L. extract against Candida albicans. Biofouling 34:880–92. https://doi.org/10.1080/08927014.2018.1514391
Samiei N, Olyaie E, Saberi S et al (2018) Development of a gum base formulation for nystatin; a new drug delivery approach for treatment of oral candidiasis. J Drug Deliv Sci Technol 48:59–65. https://doi.org/10.1016/j.jddst.2018.08.023
Sartoratto A, Machado AL, Delarmelina C et al (2004) Composition and antimicrobial activity of essential oils from aromatic plants used in Brazil. Braz J Microbiol 35:275–80. https://doi.org/10.1590/S1517-83822004000300001
Shahin M, Hady SA, Hammad M et al (2011) Novel jojoba oil-based emulsion gel formulations for clotrimazole delivery. AAPS Pharm scitech 12:239–47. https://doi.org/10.1208/s12249-011-9583-4
Sharma V, Sharma HV, Mehta D et al (2014) Comparative analysis of antibacterial and antifungal properties of traditional medicinal plants of Shimla and Solan, Himachal Pradesh. Int J Pharmacognosy Phytochem Res 6:18–26
Srivastava N, Patel DK, Rai VK et al (2018) Development of Emulgel formulation for vaginal candidiasis: Pharmaceutical characterization, in vitro and in vivo evaluation. J Drug Deliv Sci Technol 48:490–8. https://doi.org/10.1016/j.jddst.2018.10.013
Villanova JC, Ayres E, Orefice RL (2015) Design, characterization and preliminary in vitro evaluation of a mucoadhesive polymer based on modified pectin and acrylic monomers with potential use as a pharmaceutical excipient. Carbohydr Polym 121:372–81. https://doi.org/10.1016/j.carbpol.2014.12.052
Acknowledgements
We acknowledge Prem Kumar Khosla, Chancellor, the members of Yeast Biology Laboratory (YBL) and School of Pharmaceutical Sciences, Shoolini University for supporting this project. The research was promoted under the Center for Omics and Biodiversity Research Center at Shoolini University. Authors also acknowledge DST-FIST for infrastructural grant provided to Shoolini University.
Funding
None.
Author information
Authors and Affiliations
Contributions
All the experiments were performed by Prakriti Nidhi. Dr. Anuradha Sourirajan, Dr. Poonam Negi and Dr. Kamal Dev conceived the idea and provided guidance to execute the research project. All the authors have read the manuscript.
Corresponding author
Ethics declarations
Ethical statement
This article does not contain any studies with human participants or animals performed by any of the authors.
Conflict of interest
Prakriti Nidhi has no conflict of interest. Kamal Dev has no conflict of interest. Poonam Negi has no conflict of interest. Anuradha Sourirajan has no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Nidhi, P., Dev, K., Negi, P. et al. Development and evaluation of hydrogel formulation comprising essential oil of Mentha longifolia L. for oral candidiasis. ADV TRADIT MED (ADTM) 23, 777–787 (2023). https://doi.org/10.1007/s13596-022-00636-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13596-022-00636-4