In Vitro and In Vivo Evaluation of a Nano-Tool Appended Oilmix (Clove and Tea Tree Oil) Thermosensitive Gel for Vaginal Candidiasis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Cytotoxic Potential of Oilmix
2.3. Preparation of Nanoemulsion Formulations
2.3.1. Construction of Pseudo Ternary Phase Diagram
2.3.2. Phase Diagram-Based Selection of Formulations
Thermodynamic Stability Test
2.4. Characterization of Selected Nanoemulsion Formulations
2.4.1. Globule Size Analysis
2.4.2. Viscosity
2.4.3. Surface Morphology
2.4.4. Refractive Index
pH Measurement
2.5. Development of Thermosensitive Gel
2.5.1. Characterization and Evaluation of Optimized Finished Formulation (Thermo-Sensitive Gel)
2.5.2. Sol-Gel Transition Temperature
2.5.3. Viscosity Measurement
2.5.4. Mucoadhesion Test Using Texture Analyzer
2.6. Ex Vivo Drug Permeation Study
2.7. In Vivo Antifungal Studies of Optimized NE Gel
3. Results and Discussion
3.1. Cytotoxic Potential of Oilmix
3.2. Preparation of Nanoemulsion Formulations
3.2.1. Selection of Formulations from Phase Diagrams
3.2.2. Characterization of Selected Nanoemulsion Formulations
3.3. Evaluation of Thermosensitive Gel
3.3.1. Measurement of Sol-Gel Transition Temperature and Viscosity
3.3.2. Mucoadhesion Test Using Texture Analyzer
3.3.3. Ex Vivo Drug Permeation Study
3.3.4. In Vivo Antifungal Studies of Optimized NE Gel
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Soliman, S.; Alnajdy, D.; El-Keblawy, A.; Mosa, K.; Khoder, G.; Noreddin, A. Plants’ Natural Products as Alternative Promising Anti-Candida Drugs. Pharmacogn. Rev. 2017, 11, 104. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Czajkowski, K.; Broś-Konopielko, M.; Teliga-Czajkowska, J. Urinary Tract Infection in Women. Prz. Menopauzalny 2021, 20, 40–47. [Google Scholar] [CrossRef] [PubMed]
- Chayachinda, C. Acute Vaginal Candidiasis: A Review of Treatment Guidelines and Siriraj Experience. Thai J. Obstet. Gynaecol. 2021, 29, 306–312. [Google Scholar] [CrossRef]
- Palmeira-de-Oliveira, R.; Palmeira-de-Oliveira, A.; Martinez-de-Oliveira, J. New Strategies for Local Treatment of Vaginal Infections. Adv. Drug Deliv. Rev. 2015, 92, 105–122. [Google Scholar] [CrossRef] [PubMed]
- Najafi, M.N. Herbal Medicines against Bacterial Vaginosis in Women of Reproductive Age: A Systematic Review. Farmacia 2019, 67, 931–940. [Google Scholar] [CrossRef]
- Darvishi, M.; Jahdi, F.; Hamzegardeshi, Z.; Goodarzi, S.; Vahedi, M. The Comparison of Vaginal Cream of Mixing Yogurt, Honey and Clotrimazole on Symptoms of Vaginal Candidiasis. Glob. J. Health Sci. 2015, 7, 108–116. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pratha, A.A.; Priya, V.V.; Gayathri, R. Comparative Analysis of Antifungal Activity of Tea Tree and Clove Oil. Res. J. Pharm. Technol. 2016, 9, 1128. [Google Scholar] [CrossRef]
- Rahmi, D.; Yunilawati, R.; Jati, B.N.; Setiawati, I.; Riyanto, A.; Batubara, I.; Astuti, R.I. Antiaging and Skin Irritation Potential of Four Main Indonesian Essential Oils. Cosmetics 2021, 8, 94. [Google Scholar] [CrossRef]
- Lee, C.-J.; Chen, L.-W.; Chen, L.-G.; Chang, T.-L.; Huang, C.-W.; Huang, M.-C.; Wang, C.-C. Correlations of the Components of Tea Tree Oil with Its Antibacterial Effects and Skin Irritation. J. Food Drug Anal. 2013, 21, 169–176. [Google Scholar] [CrossRef] [Green Version]
- Chami, F.; Chami, N.; Bennis, S.; Trouillas, J.; Remmal, A. Evaluation of Carvacrol and Eugenol as Prophylaxis and Treatment of Vaginal Candidiasis in an Immunosuppressed Rat Model. J. Antimicrob. Chemother. 2004, 54, 909–914. [Google Scholar] [CrossRef]
- Ahmad, N.; Alam, M.K.; Shehbaz, A.; Khan, A.; Mannan, A.; Hakim, S.R.; Bisht, D.; Owais, M. Antimicrobial Activity of Clove Oil and Its Potential in the Treatment of Vaginal Candidiasis. J. Drug Target. 2005, 13, 555–561. [Google Scholar] [CrossRef] [PubMed]
- Mondello, F.; De Bernardis, F.; Girolamo, A.; Cassone, A.; Salvatore, G. In Vivo Activity of Terpinen-4-Ol, the Main Bioactive Component of Melaleuca Alternifolia Cheel (Tea Tree) Oil against Azole-Susceptible and -Resistant Human Pathogenic Candida Species. BMC Infect. Dis. 2006, 6, 158. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Smoleński, M.; Karolewicz, B.; Gołkowska, A.M.; Nartowski, K.P.; Małolepsza-Jarmołowska, K. Emulsion-Based Multicompartment Vaginal Drug Carriers: From Nanoemulsions to Nanoemulgels. Int. J. Mol. Sci. 2021, 22, 6455. [Google Scholar] [CrossRef] [PubMed]
- Pouton, C.W. Formulation of Self-Emulsifying Drug Delivery Systems. Adv. Drug Deliv. Rev. 1997, 25, 47–58. [Google Scholar] [CrossRef]
- de Siqueira, L.B.d.O.; Matos, A.P.D.S.; da Cardoso, V.S.; Villanova, J.C.O.; da Guimarães, B.C.L.R.; Dos Santos, E.P.; Beatriz Vermelho, A.; Santos-Oliveira, R.; Ricci Junior, E. Clove Oil Nanoemulsion Showed Potent Inhibitory Effect against Candida spp. Nanotechnology 2019, 30, 425101. [Google Scholar] [CrossRef] [PubMed]
- Edsman, K.; Carlfors, J.; Petersson, R. Rheological Evaluation of Poloxamer as an in Situ Gel for Ophthalmic Use. Eur. J. Pharm. Sci. 1998, 6, 105–112. [Google Scholar] [CrossRef]
- Shah, P.; Bhalodia, D.; Shelat, P. Nanoemulsion: A Pharmaceutical Review. Syst. Rev. Pharm. 2010, 1, 24. [Google Scholar] [CrossRef]
- Back, P.I.; Furtado, L.R.; Nemitz, M.C.; Balestrin, L.A.; Fachel, F.N.S.; Gomes, H.M.; Schuh, R.S.; Moreira, J.C.; von Poser, G.L.; Teixeira, H.F. Skin Permeation and Oxidative Protection Effect of Soybean Isoflavones from Topical Nanoemulsions-a Comparative Study of Extracts and Pure Compounds. AAPS Pharm. Sci. Tech. 2018, 19, 3029–3039. [Google Scholar] [CrossRef] [PubMed]
- Madhusudhan, B.; Rambhau, D.; Apte, S.S.; Gopinath, D. Oral Bioavailability of Flutamide from 1-O-Alkylglycerol Stabilized o/w Nanoemulsions. J. Dispers. Sci. Technol. 2007, 28, 1254–1261. [Google Scholar] [CrossRef]
- Chang, J.Y.; Oh, Y.K.; Choi, H.-G.; Kim, Y.B.; Kim, C.-K. Rheological Evaluation of Thermosensitive and Mucoadhesive Vaginal Gels in Physiological Conditions. Int. J. Pharm. 2002, 241, 155–163. [Google Scholar] [CrossRef]
- Ekama, S.O.; Ilomuanya, M.O.; Azubuike, C.P.; Ayorinde, J.B.; Ezechi, O.C.; Igwilo, C.I.; Salako, B.L. Enzyme Responsive Vaginal Microbicide Gels Containing Maraviroc and Tenofovir Microspheres Designed for Acid Phosphatase-Triggered Release for Pre-Exposure Prophylaxis of HIV-1: A Comparative Analysis of a Bigel and Thermosensitive Gel. Gels 2021, 8, 15. [Google Scholar] [CrossRef] [PubMed]
- Mirza, M.A.; Ahmad, S.; Mallick, M.N.; Manzoor, N.; Talegaonkar, S.; Iqbal, Z. Development of a Novel Synergistic Thermosensitive Gel for Vaginal Candidiasis: An in Vitro, in Vivo Evaluation. Colloids Surf. B Biointerfaces 2013, 103, 275–282. [Google Scholar] [CrossRef] [PubMed]
- Milani, M.; Molteni, B.; Silvani, I. Effect on Vaginal PH of a Polycarbophil Vaginal Gel Compared with an Acidic Douche in Women with Suspected Bacterial Vaginosis: A Randomized, Controlled Study. Curr. Ther. Res. Clin. Exp. 2000, 61, 781–788. [Google Scholar] [CrossRef]
- Haineault, C.; Gourde, P.; Perron, S.; Désormeaux, A.; Piret, J.; Omar, R.F.; Tremblay, R.R.; Bergeron, M.G. Thermoreversible Gel Formulation Containing Sodium Lauryl Sulfate as a Potential Contraceptive Device. Biol. Reprod. 2003, 69, 687–694. [Google Scholar] [CrossRef] [PubMed]
- Shafiq, S.; Shakeel, F.; Talegaonkar, S.; Ahmad, F.J.; Khar, R.K.; Ali, M. Development and Bioavailability Assessment of Ramipril Nanoemulsion Formulation. Eur. J. Pharm. Biopharm. 2007, 66, 227–243. [Google Scholar] [CrossRef]
- Mirza, M.A.; Talegaonkar, S.; Iqbal, Z. Particle Engineering in the Perspective of Thermodynamics: A Case Study with Itraconazole. Adv. Sci. Lett. 2012, 16, 148–158. [Google Scholar] [CrossRef]
- Deore, S.L.; Jaju, P.S.; Baviskar, B.A. Simultaneous Estimation of Four Antitussive Components from Herbal Cough Syrup by HPTLC. Int. Sch. Res. Notices 2014, 2014, 976264. [Google Scholar] [CrossRef]
- Biju, S.S.; Ahuja, A.; Rafiullah, M.R.M.; Khar, R.K. A Validated HPTLC Method for Determination of Tea Tree Oil from Cosmeceutical Formulations. J. Pharm. Biomed. Anal. 2005, 38, 41–44. [Google Scholar] [CrossRef]
- Walstra, P. Overview of Emulsion and Foam Stability. In Food Emulsions and Foams; Elsevier: Amsterdam, The Netherlands, 2005; pp. 242–257. ISBN 9781855737853. [Google Scholar]
- Kreilgaard, M.; Pedersen, E.J.; Jaroszewski, J.W. NMR Characterisation and Transdermal Drug Delivery Potential of Microemulsion Systems. J. Control. Release 2000, 69, 421–433. [Google Scholar] [CrossRef]
- Shinoda, K.; Lindman, B. Organized Surfactant Systems: Microemulsions. Langmuir 1987, 3, 135–149. [Google Scholar] [CrossRef]
- Gurny, R.; Meyer, J.-M.; Peppas, N.A. Bioadhesive Intraoral Release Systems: Design, Testing and Analysis. Biomaterials 1984, 5, 336–340. [Google Scholar] [CrossRef]
- Vijeata, A.; Chaudhary, G.R.; Chaudhary, S.; Umar, A.; Baskoutas, S. Carbon Dots Derived from Ocimum Sanctum for Dapsone–Protein Interactions: A Quantitative Approach. J. Nanostruct. Chem. 2022. [Google Scholar] [CrossRef]
- Liang, S.; Li, W.; Zhang, X.; Ma, Z.; Li, H.; Yuan, F. Evaluation of the Degradation Rates and Biocompatibility of Magnesium Pins with Different Compositions, and Processing Techniques for Oral Staplers in Vivo and in Vitro. Sci. Adv. Mater. 2021, 13, 105–114. [Google Scholar] [CrossRef]
- Vijeata, A.; Chaudhary, S.; Chaudhary, G.R.; Umar, A.; Baskoutas, S. Sustainable Agronomic Response of Carbon Quantum Dots on Allium Sativum: Translocation, Physiological Responses and Alternations in Chromosomal Aberrations. Environ. Res. 2022, 212, 113559. [Google Scholar] [CrossRef] [PubMed]
- Mu, H.; Tang, Z. Research on Inhibiting Action of MiRNA-144 with Carrier of Liposome Nanoparticle on Differentiation of Mesenchymal Stem Cells Osteogenesis. Sci. Adv. Mater. 2021, 13, 2327–2333. [Google Scholar] [CrossRef]
- Hu, S.; Lin, J.; Wu, C.; Ma, J.; Chen, S.; Chen, F. Evaluation of Circulating Tumor Cells-DNA Methylated Separation Nano-Polylactic-Co-Glycolic Acid Magnetic Beads with Epithelial Cell Adhesion Molecul/Epidermal Growth Factor Receptor Double Antibody Modification and Its Application in Lung Cancer Diagnosis. Sci. Adv. Mater. 2021, 13, 2302–2312. [Google Scholar] [CrossRef]
- Li, X.; Liu, T.; Chen, J.; Alkhanjaf, A.A.M.; Zhang, D. Ginkgolic Acid Inhibits Proliferation and Migration of Glioblastoma Cells by Inducing Cell Cycle Arrest and Apoptosis. Sci. Adv. Mater. 2021, 13, 2295–2301. [Google Scholar] [CrossRef]
- Dhiman, N.; Jasrotia, T.; Sharma, P.; Negi, S.; Chaudhary, S.; Kumar, R.; Mahnashi, M.H.; Umar, A.; Kumar, R. Immobilization Interaction between Xenobiotic and Bjerkandera Adusta for the Biodegradation of Atrazine. Chemosphere 2020, 257, 127060. [Google Scholar] [CrossRef]
- Yang, L.; Zhou, X.; Li, M.; Liao, J.; Fan, J.; Fang, S.; Zhong, W.; Chen, J. Arginine-Glycine-Aspartic-Modified Silver Nanoparticles Improve the in Vitro Anti-Cancer Efficacy of Adriamycin for Prostate Cancer Treatment. Sci. Adv. Mater. 2021, 13, 2082–2089. [Google Scholar] [CrossRef]
- Zhou, J.; Zhang, S.; Tao, Y.; Wang, J.; Chen, H.; Zhou, H. Glutaraldehyde (GLA) Loaded Albumin Nanoparticles Mediated P53 Targeting Cervical Cancer. Sci. Adv. Mater. 2021, 13, 1430–1436. [Google Scholar] [CrossRef]
- Qiu, Y.; Li, Y.; Fan, C. Application of Nanobubble-Based Ultrasound Combined with General Anesthesia for the Treatment of Colon Cancer Patients. Sci. Adv. Mater. 2021, 13, 1532–1537. [Google Scholar] [CrossRef]
- Sharma, R.; Talukdar, D.; Bhardwaj, S.; Jaglan, S.; Kumar, R.; Kumar, R.; Akhtar, M.S.; Beniwal, V.; Umar, A. Bioremediation Potential of Novel Fungal Species Isolated from Wastewater for the Removal of Lead from Liquid Medium. Environ. Technol. Innov. 2020, 18, 100757. [Google Scholar] [CrossRef]
- Kumar, P.; Saini, M.; Dehiya, B.S.; Umar, A.; Sindhu, A.; Mohammed, H.; Al-Hadeethi, Y.; Guo, Z. Fabrication and In-Vitro Biocompatibility of Freeze-Dried CTS-NHA and CTS-NBG Scaffolds for Bone Regeneration Applications. Int. J. Biol. Macromol. 2020, 149, 1–10. [Google Scholar] [CrossRef] [PubMed]
Batch Name | Compositions (% w/w) | Gelling Temperature (°C) | Viscosity (Pa.s) | MDF (g) (Mean ± SD) | MDF (g) after Dilution (Mean ± SD) |
---|---|---|---|---|---|
B 1 | 0.4% CP 934, 16% P 407 (Placebo) | 40 ± 1 | 0.906 | - | - |
B 2 | 0.4% CP 934, 16% P 407 | 40 ± 2 | 0.905 | 28.8 ± 0.4 | 22.5 ± 0.2 |
B 3 | 0.4% CP 934, 18% P 407 | 38 ± 2 | 0.911 | 30.4 ± 0.5 | 23.3 ± 0.6 |
B 4 | 0.4% CP 934, 20% P 407 | 36 ± 1 | 0.914 | 33.6 ± 0.3 | 25.4 ± 0.4 |
Batch No. | Jss ± SD (mg/cm2/h) | Permeability Coefficient (Kp, cm/h) |
---|---|---|
B 2 | 0.012 ± 0.0002 | 0.00420021 |
B 3 | 0.007 ± 0.0019 | 0.00245012 |
B 4 | 0.006 ± 0.0003 | 0.00210011 |
Group (n = 6) | Treatment |
---|---|
A | Negative control |
B | Optimized gel of Oilmix (B4) |
C | Conventional gel of TTO |
D | Conventional gel of clove oil |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Alkhanjaf, A.A.M.; Athar, M.T.; Ullah, Z.; Umar, A.; Shaikh, I.A. In Vitro and In Vivo Evaluation of a Nano-Tool Appended Oilmix (Clove and Tea Tree Oil) Thermosensitive Gel for Vaginal Candidiasis. J. Funct. Biomater. 2022, 13, 203. https://doi.org/10.3390/jfb13040203
Alkhanjaf AAM, Athar MT, Ullah Z, Umar A, Shaikh IA. In Vitro and In Vivo Evaluation of a Nano-Tool Appended Oilmix (Clove and Tea Tree Oil) Thermosensitive Gel for Vaginal Candidiasis. Journal of Functional Biomaterials. 2022; 13(4):203. https://doi.org/10.3390/jfb13040203
Chicago/Turabian StyleAlkhanjaf, Abdulrab Ahmed M., Md Tanwir Athar, Zabih Ullah, Ahmad Umar, and Ibrahim Ahmed Shaikh. 2022. "In Vitro and In Vivo Evaluation of a Nano-Tool Appended Oilmix (Clove and Tea Tree Oil) Thermosensitive Gel for Vaginal Candidiasis" Journal of Functional Biomaterials 13, no. 4: 203. https://doi.org/10.3390/jfb13040203
APA StyleAlkhanjaf, A. A. M., Athar, M. T., Ullah, Z., Umar, A., & Shaikh, I. A. (2022). In Vitro and In Vivo Evaluation of a Nano-Tool Appended Oilmix (Clove and Tea Tree Oil) Thermosensitive Gel for Vaginal Candidiasis. Journal of Functional Biomaterials, 13(4), 203. https://doi.org/10.3390/jfb13040203