Thermo-Responsive Sol-Gel-Based Nano-Carriers Containing Terbinafine HCl: Formulation, In Vitro and Ex Vivo Characterization, and Antifungal Activity
Abstract
:1. Introduction
2. Results
2.1. Formulation Optimization Data Analysis
2.2. Clarity
2.3. Composition and pH of F1–F3 Formulations
2.4. Viscosity
2.5. Gelation Temperature
2.6. Fourier Transform Infrared Spectrophotometer (FTIR)
2.7. Thermal Stability Analysis (DSC/TGA)
2.8. X-ray Diffraction (XRD)
2.9. Scanning Electron Microscopy (SEM)
2.10. Particle Size Analysis
2.11. Zeta Potential
2.12. In Vitro Drug Release Studies
2.13. Drug Permeation Studies
2.14. Antimicrobial Activity
3. Discussion
4. Conclusions
5. Material and Methods
5.1. Materials
5.2. Method of Preparing Sol-Gel-Based Nanocarriers of Terbinafine HCl
5.3. Characterization and Evaluation
5.3.1. Formulation Optimization
5.3.2. Clarity
5.3.3. pH
5.3.4. Viscosity
5.3.5. Gelation Temperature
5.3.6. Fourier Transform Infrared Spectrophotometer (FTIR)
5.3.7. Thermal Stability Analysis (DSC/TGA)
5.3.8. X-ray Diffraction (XRD)
5.3.9. Scanning Electron Microscopy (SEM)
5.3.10. Particle size Analysis
5.3.11. Zeta Potential
5.3.12. In Vitro Drug Release Studies
5.3.13. Drug Permeation Studies
5.3.14. Antimicrobial activity
5.3.15. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Dorraj, G.; Moghimi, H.R. Preparation of SLN-containing thermoresponsive in-situ forming gel as a controlled nanoparticle delivery system and investigating its rheological, thermal and erosion behavior. Iran. J. Pharm. Res. IJPR 2015, 14, 347. [Google Scholar]
- Rajput, R.L.; Narkhede, J.S.; Mujumdar, A.; Naik, J.B. Synthesis and evaluation of luliconazole loaded biodegradable nanogels prepared by pH-responsive Poly (acrylic acid) grafted Sodium Carboxymethyl Cellulose using amine based cross linker for topical targeting: In vitro and Ex vivo assessment. Polym.-Plast. Technol. Mater. 2020, 59, 1654–1666. [Google Scholar] [CrossRef]
- Wang, X.; Nada, B.A.; Gisela, S.A.; Maria, V.T.; Chritophe, H.; Martin, F.D.; Thibaud, C. Sol-gel based nanocarriers encapsulation of biomolecules and cells for medicinal applications. Curr. Top. Med. Chem. 2015, 15, 223–244. [Google Scholar] [CrossRef]
- Hamdy, R.; Fayed, B.; Hamoda, A.M.; Qalaji, M.R.; Haider, M.; Soliman, S.S.M. Essential oil-based design and development of novel anti-Candida azoles formulation. Molecules 2020, 25, 1463. [Google Scholar] [CrossRef]
- Carrillo Muñoz, A.J.; Finquelievich, J.; Tur-Tur, C.; Eraso, E.; Jauregizar, N.; Quindos, G.; Giusiano, G. Combination antifungal therapy: A strategy for the management of invasive fungal infections. Rev. Esp. Quimioter. 2014, 27, 141–158. [Google Scholar]
- Aragón-Sánchez, J.; Lopez-Valverde, M.E.; Torres-Sopena, L.; Viquez-Molina, G.; Milagro-Beamonte, A. Onychomycosis and tinea pedis in the feet of patients with diabetes. Int. J. Low. Extrem. Wounds 2023, 22, 321–327. [Google Scholar] [CrossRef]
- Revankar, S.G.; Nailor, M.D.; Sobel, J.D. Use of terbinafine in rare and refractory mycoses. Future Microbiol. 2008, 3, 9–17. [Google Scholar] [CrossRef] [PubMed]
- Sigurgeirsson, B.; Hay, R.J. The antifungal drugs used in skin disease. In Antibiotic and Antifungal Therapies in Dermatology; Springer: Berlin/Heidelberg, Germany, 2016; pp. 141–156. [Google Scholar]
- Krawczyk-Santos, A.P.; Marreto, R.N.; Concheiro, A.; Alvarez-Lorenzo, C.; Taveira, S.F. Poly (pseudo) rotaxanes formed by mixed micelles and α-cyclodextrin enhance terbinafine nail permeation to deeper layers. Int. J. Pharm. X 2022, 4, 100118. [Google Scholar] [CrossRef] [PubMed]
- Shalviri, A.; Liu, Q.; Abdekhodaie, M.J.; Wu, X.Y. Novel modified starch–xanthan gum hydrogels for controlled drug delivery: Synthesis and characterization. Carbohydr. Polym. 2010, 79, 898–907. [Google Scholar] [CrossRef]
- Pervaiz, F.; Mushtaq, R.; Noreen, S. Formulation and optimization of terbinafine HCl loaded chitosan/xanthan gum nanoparticles containing gel: Ex-vivo permeation and in-vivo antifungal studies. J. Drug Deliv. Sci. Technol. 2021, 66, 102935. [Google Scholar] [CrossRef]
- Karekar, P.; Salunkhe, N.; Yadav, A.; Bangar, D.; Yadav, D. Modulation of Physico-Chemical Properties of Terbinafine HCl by Using Solid Dispersion Technique. Res. J. Pharm. Technol. 2014, 7, 450–453. [Google Scholar]
- Prausnitz, M.R.; Langer, R. Transdermal drug delivery. Nat. Biotechnol. 2008, 26, 1261–1268. [Google Scholar] [CrossRef] [PubMed]
- Giri, Y.; Behera, A.; Mohanty, B.; Pattnaik, G.; Habibullah, S.K. Transungual Drug Delivery System for the Topical Treatment of Onychomycosis: A Review. Drug Deliv. Lett. 2022, 12, 2–18. [Google Scholar] [CrossRef]
- Dutta, S.; Ganguly, B.N. Characterization of ZnO nanoparticles grown in presence of Folic acid template. J. Nanobiotechnol. 2012, 10, 29. [Google Scholar] [CrossRef]
- Kesharwani, P.; Fatima, M.; Singh, V.; Sheikh, A.; Almalki, W.H.; Gajbhiye, V.; Sahebkar, A. Itraconazole and difluorinated-curcumin containing chitosan nanoparticle loaded hydrogel for amelioration of onychomycosis. Biomimetics 2022, 7, 206. [Google Scholar] [CrossRef]
- Waqar, M.A.; Zaman, M.; Hameed, H.; Munir, M. Ethosomes: A novel approach for the delivery of drug. Int. J. Pharm. Integr. Health Sci. 2023, 4, 31–46. [Google Scholar]
- Jafari, A.; Daneshamouz, S.; Ghasemiyeh, P.; Mohammadi-Samani, S. Ethosomes as dermal/transdermal drug delivery systems: Applications, preparation and characterization. J. Liposome Res. 2023, 33, 34–52. [Google Scholar] [CrossRef]
- Gao, C.; Liao, J.; Lu, J.; Ma, J.; Kianfar, E. The effect of nanoparticles on gas permeability with polyimide membranes and network hybrid membranes: A review. Rev. Inorg. Chem. 2021, 41, 1–20. [Google Scholar] [CrossRef]
- Alkholief, M.; Kalam, M.A.; Almomen, A.; Alshememry, A.; Alshamsan, A. Thermoresponsive Sol-gel based nanocarriers improves ocular bioavailability of Dipivefrin hydrochloride and potentially reduces the elevated intraocular pressure in vivo. Saudi Pharm. J. 2020, 28, 1019–1029. [Google Scholar] [CrossRef]
- Arafat, M.; Ahmed, Z.; Arafat, O. Comparison between generic drugs and brand name drugs from bioequivalence and thermoequivalence prospective. Int. J. Pharm. Pharm. Sci. 2017, 9, 100118. [Google Scholar] [CrossRef]
- Lipner, S.R.; Scher, R.K. Onychomycosis: Treatment and prevention of recurrence. J. Am. Acad. Dermatol. 2019, 80, 853–867. [Google Scholar] [CrossRef]
- Montgomery, D.C. Design and Analysis of Experiments; John Wiley & Sons: Hoboken, NJ, USA, 2017. [Google Scholar]
- Hirun, N.; Kraisit, P.; Tantishaiyakul, V. Thermosensitive polymer blend composed of poloxamer 407, poloxamer 188 and polycarbophil for the use as mucoadhesive in situ gel. Polymers 2022, 14, 1836. [Google Scholar] [CrossRef]
- Bennani, I.; Chentoufi, M.A.; Cheikh, A.; Karbane, M.E.; Bouatia, M. Proposal of a simple and rapid method for the chemotherapy preparations analytical control by spectrophotometry UV-Vis method. J. Oncol. Pharm. Pract. 2021, 27, 99–107. [Google Scholar] [CrossRef]
- Li, J.; Liu, H.; Liu, L.; Cai, C.; Xin, H.; Liu, W. Design and evaluation of a brinzolamide drug–resin in situ thermosensitive gelling system for sustained ophthalmic drug delivery. Chem. Pharm. Bull. 2014, 62, 1000–1008. [Google Scholar] [CrossRef] [PubMed]
- Koga, H.; Nanjoh, Y.; Makimura, K.; Tsuboi, R. In vitro antifungal activities of luliconazole, a new topical imidazole. Med. Mycol. 2009, 47, 640–647. [Google Scholar] [CrossRef]
- Sarika, G.; Shivappa, N.; Shanta, G.; Avinash, B. Formulation and evaluation of topical microemulgel containing terbinafine hydrochloride. J. Pharm. Res. Int. 2021, 33, 794–803. [Google Scholar]
- Movasaghi, Z.; Rehman, S.; Rehman, I.U. Fourier transform infrared (FTIR) spectroscopy of biological tissues. Appl. Spectrosc. Rev. 2008, 43, 134–179. [Google Scholar] [CrossRef]
- Khan, S.; Madni, A.; Rahim, M.A.; Shah, H.; Jabar, A. Enhanced in vitro release and permeability of glibenclamide by proliposomes: Development, characterization and histopathological evaluation. J. Drug Deliv. Sci. Technol. 2021, 63, 102450. [Google Scholar] [CrossRef]
- Ahmed, S.; Ibrahim, M.A.; Sarhan, H.A.; Amin, M.A. Formulation and characterization of biodegradable chitosan films for topical application of terbinafine HCl. Bulletin of Pharmaceutical Sciences. Assiut 2007, 30, 111–129. [Google Scholar]
- Khan, H.; Yerramilli, A.S.; Oliveira, A.D.; Alford, T.L.; DC Boffito, D.C.; Patience, G.S. Experimental methods in chemical engineering: X-ray diffraction spectroscopy—XRD. Can. J. Chem. Eng. 2020, 98, 1255–1266. [Google Scholar] [CrossRef]
- Ali, A.; Chiang, Y.W.; Santos, R.M. X-ray diffraction techniques for mineral characterization: A review for engineers of the fundamentals, applications, and research directions. Minerals 2022, 12, 205. [Google Scholar] [CrossRef]
- Carlson, B.D.; Donavan, D.T. Concerning the effect of athlete endorsements on brand and team-related intentions. Sport Mark. Q. 2008, 17, 154–162. [Google Scholar]
- Kondoros, B.A.; Jójárt-Laczkovich, O.; Berkesi, O.; Szabó-Révész, P.; Csóka, I.; Ambrus, R.; Aigner, Z. Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations. Pharmaceutics 2022, 14, 744. [Google Scholar] [CrossRef] [PubMed]
- Fernando, S.; Gunasekara, C.; Law, D.W.; Nasvi, M.C.M.; Setunge, S.; Dissanayake, R. Engineering properties of waste-based alkali activated concrete brick containing low calcium fly ash and rice husk ash: A comparison with traditional Portland cement concrete brick. J. Build. Eng. 2022, 46, 103810. [Google Scholar] [CrossRef]
- Clogston, J.D.; Patri, A.K. Zeta potential measurement. In Characterization of Nanoparticles Intended for Drug Delivery; Springer: Berlin/Heidelberg, Germany, 2011; pp. 63–70. [Google Scholar]
- El-Saharty, Y.S.; Hassan, N.Y.; Metwally, F.H. Simultaneous determination of terbinafine HCL and triamcinolone acetonide by UV derivative spectrophotometry and spectrodensitometry. J. Pharm. Biomed. Anal. 2002, 28, 569–580. [Google Scholar] [CrossRef] [PubMed]
- Kumar, M.; Sharma, A.; Mahmood, S.; Thakur, A.; Mirza, M.A.; Bhatia, A. Franz diffusion cell and its implication in skin permeation studies. J. Dispers. Sci. Technol. 2023, 1–14. [Google Scholar] [CrossRef]
- Machado, R.M.; Palmeira-de-Oliveira, A.; Gaspar, C.; Martinez-de-Oliveira, J.; Palmeira-de-Oliveira, R. Studies and methodologies on vaginal drug permeation. Adv. Drug Deliv. Rev. 2015, 92, 14–26. [Google Scholar] [CrossRef]
- Doijad, R.; Manvi, F.V.; Malleswara, V.S.N.; Alase, P. Sustained Ophthalmic Delivery of Gatifloxacin from In Situ Gelling System. Indian J. Pharm. Sci. 2006, 68, 814–818. [Google Scholar] [CrossRef]
- Ali, S.M.; Yosipovitch, G. Skin pH: From basic science to basic skin care. Acta Derm.-Venereol. 2013, 93, 261–267. [Google Scholar] [CrossRef]
- Suresh, R.; Ramakrishna, B.; Chatap, V.K. Development and evaluation of terbinafine hydrochloride nano-gel formulation for the topical treatment of onychomycosis. Acta Biomed. 2023, 94, 1751–1760. [Google Scholar]
- Gunasekara, C.; Law, D.W.; Setunge, S.; Sanjayan, J.G. Zeta potential, gel formation and compressive strength of low calcium fly ash geopolymers. Constr. Build. Mater. 2015, 95, 592–599. [Google Scholar] [CrossRef]
- Nägele, E. The zeta-potential of cement. Cem. Concr. Res. 1985, 15, 453–462. [Google Scholar] [CrossRef]
- Moraes, R.R.; Garcia, J.W.; Barros, M.D.; Lewis, S.H.; Pfeifer, C.S.; Liu, J.; Stansbury, J.W. Control of polymerization shrinkage and stress in nanogel-modified monomer and composite materials. Dent. Mater. 2011, 27, 509–519. [Google Scholar] [CrossRef] [PubMed]
- Meng, N.; Zhou, N.; Zang, S.; Shen, J. Synthesis and antifungal activities of polymer/montmorillonite–terbinafine hydrochloride nanocomposite films. Appl. Clay Sci. 2009, 46, 136–140. [Google Scholar] [CrossRef]
- Sudhakar, B.; Varma, J.R.; Murthy, K.R. Formulation, characterization and ex vivo studies of terbinafine HCl liposomes for cutaneous delivery. Curr. Drug Deliv. 2014, 11, 521–530. [Google Scholar] [CrossRef]
- Meng, N.; Zhou, N.-L.; Shen, J. Terbinafine hydrochloride intercalated in montmorillonite: Synthesis and characterization. Res. Chem. Intermed. 2013, 39, 671–680. [Google Scholar] [CrossRef]
- Cheng, Y.-H.; Cheng, Y.-F.; Ko, Y.-C.; Liu, C.J.-L. Development of a dual delivery of levofloxacin and prednisolone acetate via PLGA nanoparticles/thermosensitive chitosan-based hydrogel for postoperative management: An in-vitro and ex-vivo study. Int. J. Biol. Macromol. 2021, 180, 365–374. [Google Scholar] [CrossRef] [PubMed]
- Seenivasan, R.; Iyer, S.S.; Narayanasamy, V.P.; Krishnan, V.; Anand, M.I.; Venkatesh, D.N. Solubility enhancement of terbinafine hydrochloride by hydrotropic technique. J. Med. Pharm. Allied Sci. 2023, 12, 5596–5603. [Google Scholar]
- Qian, S.; Wong, Y.C.; Zuo, Z. Development, characterization and application of in situ gel systems for intranasal delivery of tacrine. Int. J. Pharm. 2014, 468, 272–282. [Google Scholar] [CrossRef]
- Dwiecki, P.M.; Michalak, T.K.; Muszalska-Kolos, I. Assessment of the properties of terbinafine hydrochloride and the search route for antifungal agents. J. Mol. Struct. 2022, 1252, 132225. [Google Scholar] [CrossRef]
Run | (X1) Polox407 (%) | (X2) Polox88 (%) | (R1) Gelation Temp (°C) | (R1) Gelation Time (S) |
---|---|---|---|---|
1 | 10 | 15 | 32.8 | 0.702513 |
2 | 10 | 12.5 | 35.9 | 0.910204 |
3 | 20 | 10 | 30 | 0.59545 |
4 | 10 | 12.5 | 35.9 | 0.869 |
5 | 15 | 10 | 37 | 0.95282 |
6 | 20 | 12.5 | 34 | 0.80619 |
7 | 15 | 15 | 38.2 | 1.095 |
8 | 15 | 15 | 38.2 | 1.095 |
9 | 20 | 15 | 32 | 0.70619 |
10 | 10 | 10 | 40.1 | 1.19751 |
Variables | Gelation Temperature °C | Gelling Time (s) |
---|---|---|
F1 | 38.82 | 67 |
A (poloxamer 407(A1)) | −1.84 | −0.09 |
B (poloxamer 188 (B2)) | −0.36 | −0.0125 |
AB | 2.33 | 0.1514 |
A2 | −3.87 | −0.22 |
B2 | −1.22 | −0.047 |
Model p value | 0.01 | 0.001 |
R2 | 0.85 | 0.77 |
Adjusted R2 | 0.73 | 0.58 |
F Value | 7.09 | 4.16 |
Formulation | Drug (mg) | Poloxamer 407 (mg) | Poloxamer 188 (mg) | pH |
---|---|---|---|---|
F1 | 10 | 20 | 18 | 5.7 ± 0.18 |
F2 | 10 | 21 | 13 | 5.8 ± 0.16 |
F3 | 10 | 25 | 15 | 5.9 ± 0.18 |
Formulation | Viscosity (Cps) |
---|---|
F1 | 15500 ± 2.45 |
F2 | 12900 ± 3.26 |
F3 | 16000 ± 2.98 |
Formulation | Gelation Temperature (°C) |
---|---|
F1 | 28 ± 0.09 |
F2 | 34 ± 0.06 |
F3 | 27 ± 0.08 |
Name | Units | Low | High | −Alpha | +Alpha |
---|---|---|---|---|---|
Polox 407 | % | 10 | 20 | 4.26 | 5.72 |
Polox 188 | % | 10 | 15 | 2.13 | 4.84 |
Trials | Drug (mg) | Poloxamer 407 (mg) | Poloxamer 188 (mg) |
---|---|---|---|
1 | 10 | 18 | 15 |
2 | 10 | 21.5 | 17.5 |
3 | 10 | 25 | 15 |
4 | 10 | 18 | 20 |
5 | 10 | 21.5 | 13.96 |
6 | 10 | 21 | 13 |
7 | 10 | 16.55 | 17.5 |
8 | 10 | 26.5 | 12.5 |
9 | 10 | 20 | 18 |
10 | 10 | 25 | 30 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 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
Bajwa, M.; Tabassam, N.; Hameed, H.; Irfan, A.; Zaman, M.; Khan, M.A.; Shazly, G.A.; Mehboob, T.; Riaz, T.; Jardan, Y.A.B. Thermo-Responsive Sol-Gel-Based Nano-Carriers Containing Terbinafine HCl: Formulation, In Vitro and Ex Vivo Characterization, and Antifungal Activity. Gels 2023, 9, 830. https://doi.org/10.3390/gels9100830
Bajwa M, Tabassam N, Hameed H, Irfan A, Zaman M, Khan MA, Shazly GA, Mehboob T, Riaz T, Jardan YAB. Thermo-Responsive Sol-Gel-Based Nano-Carriers Containing Terbinafine HCl: Formulation, In Vitro and Ex Vivo Characterization, and Antifungal Activity. Gels. 2023; 9(10):830. https://doi.org/10.3390/gels9100830
Chicago/Turabian StyleBajwa, Maryam, Naila Tabassam, Huma Hameed, Ali Irfan, Muhammad Zaman, Mahtab Ahmad Khan, Gamal A. Shazly, Tooba Mehboob, Tehseen Riaz, and Yousef A. Bin Jardan. 2023. "Thermo-Responsive Sol-Gel-Based Nano-Carriers Containing Terbinafine HCl: Formulation, In Vitro and Ex Vivo Characterization, and Antifungal Activity" Gels 9, no. 10: 830. https://doi.org/10.3390/gels9100830