• P-ISSN 0973-7200 E-ISSN 2454-8405
  • Follow us

Journal of Pharmaceutical Research

Article

Topical Delivery of Voriconazole Loaded on Lyotropic Liquid Crystal Gel for Management of Fungal Infections
  • VIEWS 236
  • PDF 64

Journal of Pharmaceutical Research

DOI: 10.18579/jopcr/v23.2.32

Year: 2024, Volume: 23, Issue: 2, Pages: 89-106

Original Article

Topical Delivery of Voriconazole Loaded on Lyotropic Liquid Crystal Gel for Management of Fungal Infections

Mohamed A Attia Shafie1,∗, Maha Abdel-Azeem Hassan Mohamed1, Ahmed Abd-El Zaher Saadi Mohamed1

1Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt

*Corresponding Author
Email: [email protected]

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Topical antifungal therapy is recommended for the treatment of fungal infections of the skin. Due to its benefits, including the ability to direct drugs to the infection site and a lower chance of systemic adverse effects. The nano size and structure of LLC with the skin enhance the permeation and deposition of drugs within deep parts of skin. In this a novel formulation of voriconazole LLC gel was planned. Surfactant, co-surfactant, oil, and water pseudo-ternary phase diagrams were created in order to determine the LLC gel and microemulsion zones. The formulations were evaluated using polarizing microscopy, FT-IR spectroscopy. For each formulation, the polydispersity index, zeta potential, and mean droplet size were determined. The release patterns revealed that the prepared LLC gel provide sustained release profile up to 24 hr. Ex-vivo permeation of selected formulations exhibited higher permeability values for voriconazole. The drug skin deposition results from selected formulations showed that, in comparison to other studied formulations, a much larger amount of the drug was deposited in the skin after 24 hours. The confocal pictures appeared that the LLC gel was able to provide fluorescent color to all skin layers. The skin irritation study data of LLC gel formulations could be announced as safe and non- irritant for human skin. The selected formulations underwent a six-month stability testing at room temperature and 4–8 °C. The results showed that the pH, drug content, and viscosity values did not change significantly during this time.

Keywords: Lyotropic liquid crystal, Release and diffusion, Skin permeability, Skin deposition, Pathohistology

References

  2. Mumtaz T, Ahmed N, Hassan Nu, Badshah M, Khan S, Rehman Au. Voriconazole nanoparticles-based film forming spray: An efficient approach for potential treatment of topical fungal infections. Journal of Drug Delivery Science and Technology. 2022;70. Available from: https://doi.org/10.1016/j.jddst.2021.102973
  3. Shah MKA, Azad AK, Nawaz A, Ullah S, Latif MS, Rahman H, et al. Formulation Development, Characterization and Antifungal Evaluation of Chitosan NPs for Topical Delivery of Voriconazole In Vitro and Ex Vivo. Polymers. 2022;14(1):1–17. Available from: https://doi.org/10.3390/polym14010135
  4. Liu W, Li M, Tian B, Yang X, Du W, Wang X, et al. Calcofluor white-cholesteryl hydrogen succinate conjugate mediated liposomes for enhanced targeted delivery of voriconazole into Candida albicans. Biomaterials Science. 2023;11(1):307–321. Available from: https://doi.org/10.1039/D2BM01263D
  5. Song SH, Lee KM, Kang JB, Lee SG, Kang MJ, Choi YW. Improved skin delivery of voriconazole with a nanostructured lipid carrier-based hydrogel formulation. Chemical and Pharmaceutical Bulletin. 2014;62(8):793–798. Available from: https://doi.org/10.1248/cpb.c14-00202
  6. Raju YP, Hyndavi N, Chowdary VH, Rajesh SN, Basha D, Tejeswari N. In vitro assessment of non-irritant microemulsified voriconazole hydrogel system. Artificial Cells, Nanomedicine, and Biotechnology . 2017;45(8):1539–1547. Available from: https://doi.org/10.1080/21691401.2016.1260579
  7. Singh VK, Pal K, Banerjee I, Pramanik K, Anis A, SMAZ. Novel organogel based lyotropic liquid crystal physical gels for controlled delivery applications. European polymer journal. 2015;68:326–337. Available from: https://doi.org/10.1016/j.eurpolymj.2015.05.009
  8. Kumar R, Sinha VR. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids and Surfaces B: Biointerfaces. 2014;117:82–88. Available from: https://doi.org/10.1016/j.colsurfb.2014.02.007
  9. Kim YH, Song CK, Jung E, Kim DH, Kim DD. A microemulsion-based hydrogel formulation containing voriconazole for topical skin delivery. Journal of Pharmaceutical Investigation . 2014;44(7):517–524. Available from: https://doi.org/10.1007/s40005-014-0159-7
  10. Morsi NM, Abdelbary GA, MAA. Silver sulfadiazine based cubosome hydrogels for topical treatment of burns: Development and in vitro/in vivo characterization. European journal of pharmaceutics and biopharmaceutics. 2014;86(2):178–189. Available from: https://doi.org/10.1016/j.ejpb.2013.04.018
  11. Benigni M, Pescina S, Grimaudo MA, Padula C, Santi P, SN. Development of microemulsions of suitable viscosity for cyclosporine skin delivery. International journal of pharmaceutics. 2018;545(1-2):197–205. Available from: https://doi.org/10.1016/j.ijpharm.2018.04.049
  12. Nikumbh KV, Sevankar SG, Patil MP. Formulation development, in vitro and in vivo evaluation of microemulsion-based gel loaded with ketoprofen. Drug Delivery . 2015;22(4):509–515. Available from: https://doi.org/10.3109/10717544.2013.859186
  14. Abdulkarim MF, Abdullah GZ, Chitneni M, Salman IM, Ameer OZ, Yam MF, et al. Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream. International Journal of Nanomedicine. 2010;5(1):915–924. Available from: https://doi.org/10.2147%2FIJN.S13305
  15. Safwat MA, Soliman GM, Sayed D, Attia MA. Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil. Drug Development and Industrial Pharmacy. 2017;43(11):1780–1791. Available from: https://doi.org/10.1080/03639045.2017.1339082
  16. Qurt MS, Esentürk İ, Tan SB, Erdal MS, Araman A, Güngör S. Voriconazole and sertaconazole loaded colloidal nano-carriers for enhanced skin deposition and improved topical fungal treatment. Journal of Drug Delivery Science and Technology. 2018;48:215–222. Available from: https://doi.org/10.1016/j.jddst.2018.09.020
  17. Guide for the care and use of laboratory animals. (Vol. 8, pp. 1-246) Washington, D.C.USA. National Academies Press..
  18. Abdellatif MM, Khalil IA, Khalil MAF. Sertaconazole nitrate loaded nanovesicular systems for targeting skin fungal infection: In-vitro, ex-vivo and in-vivo evaluation. International Journal of Pharmaceutics. 2017;527(1-2):1–11. Available from: https://doi.org/10.1016/j.ijpharm.2017.05.029
  19. Al-Maghrabi PM, Khafagy ES, Ghorab MM, Gad S. Influence of formulation variables on miconazole nitrate-loaded lipid based nanocarrier for topical delivery. Colloids and Surfaces B: Biointerfaces. 2020;193. Available from: https://doi.org/10.1016/j.colsurfb.2020.111046
  20. Guo F, Wang J, Ma M, Tan F, Li N. Skin targeted lipid vesicles as novel nano-carrier of ketoconazole: characterization, in vitro and in vivo evaluation. Journal of Materials Science: Materials in Medicine. 2015;26(4):1–13. Available from: https://doi.org/10.1007/s10856-015-5487-2
  21. Moretti A, Boncio L, Posteraro B, Mechelli L, Balducci M, Fadda G, et al. Co-cutaneous infection in a dog: PCR-reverse identification of Candida tropicalis on skin biopsy. Journal de Mycologie Médicale. 2006;16(1):30–36. Available from: https://doi.org/10.1016/j.mycmed.2006.01.004
  22. Mei L, Xie Y, Huang Y, Wang B, Chen J, Quan G, et al. Injectable in situ forming gel based on lyotropic liquid crystal for persistent postoperative analgesia. Acta Biomaterialia. 2018;67:99–110. Available from: https://dx.doi.org/10.1016/j.actbio.2017.11.057
  23. Khare A, Singh I, Pawar P, Grover K. Design and evaluation of voriconazole loaded solid lipid nanoparticles for ophthalmic application. Journal of drug delivery. 2016;2016:1–11. Available from: https://doi.org/10.1155/2016/6590361
  25. Petrović ZS. Polyurethanes from Vegetable Oils. Polymer Reviews. 2008;48(1):109–155. Available from: https://www.tandfonline.com/doi/abs/10.1080/15583720701834224
  26. Mirghani MES, Man YBC, Jinap S, Baharin BS, Bakar J. Application of FTIR spectroscopy in determining sesamol in sesame seed oil. Journal of the American Oil Chemists' Society. 2003;80(1):1–4. Available from: https://dx.doi.org/10.1007/s11746-003-0640-1
  29. Cardoso CO, Ferreira-Nunes R, Cunha-Filho M, Gratieri T, Gelfuso GM. In situ gelling microemulsion for topical ocular delivery of moxifloxacin and betamethasone. Journal of Molecular Liquids. 2022;360. Available from: https://dx.doi.org/10.1016/j.molliq.2022.119559
  30. Moreno MA, Ballesteros MP, Frutos P. Lecithin-based oil-in-water microemulsions for parenteral use: Pseudoternary phase diagrams, characterization and toxicity studies. Journal of Pharmaceutical Sciences. 2003;92(7):1428–1437. Available from: https://dx.doi.org/10.1002/jps.10412
  32. Patel RB, Patel MR, Bhatt KK, Patel BG. Formulation consideration and characterization of microemulsion drug delivery system for transnasal administration of carbamazepine. Bulletin of Faculty of Pharmacy, Cairo University. 2013;51(2):243–253. Available from: https://doi.org/10.1016/j.bfopcu.2013.07.002
  33. Bikkad ML, Nathani AH, Mandlik SK, Shrotriya SN, Ranpise NS. Halobetasol propionate-loaded solid lipid nanoparticles (sln) for skin targeting by topical delivery. Journal of Liposome Research . 2014;24(2):113–123. Available from: https://doi.org/10.3109/08982104.2013.843192
  34. Shewaiter MA, Hammady TM, El-Gindy A, Hammadi SH, Gad S. Formulation and characterization of leflunomide/diclofenac sodium microemulsion base-gel for the transdermal treatment of inflammatory joint diseases. Journal of Drug Delivery Science and Technology. 2021;61. Available from: https://doi.org/10.1016/j.jddst.2020.102110
  35. Patel P, Pol A, Kalaria D, Date AA, Kalia Y, Patravale V. Microemulsion-based gel for the transdermal delivery of rasagiline mesylate: In vitro and in vivo assessment for parkinson’s therapy. European Journal of Pharmaceutics and Biopharmaceutics. 2021;165:66–74. Available from: https://doi.org/10.1016/j.ejpb.2021.04.026
  36. Savic S, Pantelic I, Lukic M, Markovic B, Milic J. Behind the Alkyl Polyglucoside-based structures: Lamellar liquid crystalline and lamellar gel phases in different emulsion systems. In: Alkyl Polyglucosides. (pp. 21-52) Elsevier. 2014.
  37. Li Q, Cao J, Li Z, XC. Cubic Liquid Crystalline Gels Based on Glycerol Monooleate for Intra-articular Injection. AAPS PharmSciTech. 2018;19:858–865. Available from: https://doi.org/10.1208/s12249-017-0894-y
  38. Makai M, Csányi E, Németh Z, Palinkas J, Erős I. Structure and drug release of lamellar liquid crystals containing glycerol. International Journal of Pharmaceutics. 2003;256(1-2):95–107. Available from: https://doi.org/10.1016/S0378-5173(03)00066-8
  39. El-Hadidy GN, Ibrahim HK, Mohamed MI, El-Milligi MF. Microemulsions as vehicles for topical administration of voriconazole: formulation and in vitro evaluation. Drug Development and Industrial Pharmacy. 2012;38(1):64–72. Available from: https://doi.org/10.3109/03639045.2011.590731
  40. Rapalli VK, Waghule T, Hans N, Mahmood A, Gorantla S, Dubey SK, et al. Insights of lyotropic liquid crystals in topical drug delivery for targeting various skin disorders. Journal of molecular liquids. 2020;315. Available from: https://doi.org/10.1016/j.molliq.2020.113771
  41. Luo M, Shen Q, JC. Transdermal delivery of paeonol using cubic gel and microemulsion gel. International Journal of Nanomedicine. 2011;6:1603–1610. Available from: https://doi.org/10.2147%2FIJN.S22667
  42. Elmataeeshy ME, Sokar MS, Bahey-El-Din M, Shaker DS. Enhanced transdermal permeability of terbinafine through novel nanoemulgel formulation; development, in vitro and in vivo characterization. Future journal of pharmaceutical sciences. 2018;4(1):18–28. Available from: https://doi.org/10.1016/j.fjps.2017.07.003
  43. Mazzotta E, Rossi CO, Muzzalupo R. Different BRIJ97 colloid systems as potential enhancers of acyclovir skin permeation and depot. Colloids and Surfaces B: Biointerfaces. 2019;173:623–631. Available from: https://doi.org/10.1016/j.colsurfb.2018.10.041
  44. Zhang J, Michniak-Kohn BB. Investigation of microemulsion and microemulsion gel formulations for dermal delivery of clotrimazole. International Journal of Pharmaceutics. 2018;536(1):345–352. Available from: https://doi.org/10.1016/j.ijpharm.2017.11.041
  45. Draize JH, Woodard G, Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. Journal of Pharmacology and Experimental Therapeutics. 1944;82(3):377–390. Available from: https://jpet.aspetjournals.org/content/82/3/377
  46. Bachhav YG, Patravale VB. Microemulsion based vaginal gel of fluconazole: Formulation, in vitro and in vivo evaluation. International Journal of Pharmaceutics. 2009;365(1-2):175–179. Available from: https://doi.org/10.1016/j.ijpharm.2008.08.021
  47. Okur NÜ, Yozgatlı V, Okur ME, Yoltaş A, Siafaka PI. Improving therapeutic efficacy of voriconazole against fungal keratitis: Thermo-sensitive in situ gels as ophthalmic drug carriers. Journal of Drug Delivery Science and Technology. 2019;49:323–333. Available from: https://doi.org/10.1016/j.jddst.2018.12.005
  49. Pajic NB, Nikolic I, Mitsou E, Papadimitriou V, Xenakis A, Randjelovic D, et al. Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. Journal of molecular liquids. 2018;272:746–758. Available from: https://doi.org/10.1016/j.molliq.2018.10.002

Copyright

© 2024 Published by Krupanidhi College of Pharmacy. This is an open-access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/) 

  • 06 August 2024

Year: 2024, Volume: 23, Issue: 2


More articles

DON'T MISS OUT!

Subscribe now for latest articles and news.