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Design and development of Amphotericin-B loaded transungual drug delivery system for the effective management of onychomycosis

Year 2025, Volume: 29 Issue: 1, 210 - 221

Abstract

The present research aims to formulate and evaluate the emulgel containing different penetration enhancers for the transungual delivery of Amphotericin B (AmB). Amphotericin B is a widely used antifungal agent in treating infections caused by Candida, Aspergillus, and Fusarium, which are also responsible organisms for onychomycosis. The emulsions were prepared using the fusion method of oil, surfactant, co-surfactant, and distilled water. The formulated emulsions were homogenized with a high-speed homogenizer to reduce globule size and incorporated into the gel base of different concentrations. The formulation undergoes physical evaluations, as well as spreadability, extrudability, washability, viscosity, and in-vitro drug release studies. EG5 was selected as an optimized Formulation from the drug release study as it showed a better release profile. Different penetration enhancers were added and further evaluated in the optimized formulation for parameters like in-vitro drug release, drug uptake, and stability study. Physical characteristics, spreadability, extrudability, washability, and viscosity of all the prepared emulgels were acceptable. Optimized formulation EG-5SS showed better drug release, uptake, and oil binding capacity. All the studies concluded that the EG-5SS was the best formulation and sodium sulfide could be used as a potential permeation enhancer.

References

  • [1] Kaur R, Kashyap B, Bhalla P. Onychomycosis-epidemiology, diagnosis and management. Indian J Med Microbiol. 2008; 26(2): 108-116. https://doi.org/10.1016/S0255-0857(21)01924-1
  • [2] Giri Y, Behera A, Mohanty B, Pattnaik G, Habibullah SK. Transungual drug delivery system for the topical treatment of onychomycosis: A review. Drug Deliv Lett. 2022; 12(1): 2-18. https://doi.org/10.2174/2210303112666220224110100
  • [3] Baran R, Haneke E, Hay RJ, Piraccini BM, Tosti A. Onychomycosis: the current approach to diagnosis and therapy. CRC Press, Florida, USA 1999.
  • [4] Nikitha S, Kondraganti N, Kandi V, Kondraganti IV N. Total dystrophic onychomycosis of all the nails caused by non-dermatophyte fungal species: a case report. Cureus. 2022 Sep 29;14(9):e29765. https://doi.org/10.7759/cureus.29765
  • [5] Baswan SM, Li SK, LaCount TD, Kasting GB. Size and charge dependence of ion transport in human nail plate. J Pharm Sci. 2016; 105(3): 1201-1208. https://doi.org/10.1016/j.xphs.2015.12.011
  • [6] Torrado JJ, Espada R, Ballesteros MP, Torrado-Santiago S. Amphotericin B formulations and drug targeting. J. Pharm Sci. 2008; 97(7): 2405-2425. https://doi.org/10.1002/jps.21179
  • [7] Odds FC, Brown AJ, Gow NA. Antifungal agents: mechanisms of action. Trends Microbiol. 2003; 11(6): 272-279. https://doi.org/10.1016/S0966-842X(03)00117-3
  • [8] Arendrup MC, Cuenca-Estrella M, Lass-Flörl C, Hope WW, European Committee on Antimicrobial Susceptibility Testing Subcommittee on Antifungal Susceptibility Testing (EUCAST-AFST. EUCAST technical note on Aspergillus and amphotericin B, itraconazole, and posaconazole. Clin Microbiol Infect. 2012; 18(7): E248-250 https://doi.org/10.1111/j.1469-0691.2012.03890.x
  • [9] Lurati M, Baudraz-Rosselet F, Vernez M, Spring P, Bontems O, Fratti M, Monod M. Efficacious treatment of non dermatophyte mould onychomycosis with topical amphotericin B. Dermatology. 2012; 223(4): 289-292. https://doi.org/10.1159/000335093
  • [10] De Kruijff B, Demel RA. Polyene antibiotic-sterol interactions in membranes of Acholeplasmalaidlawii cells and lecithin liposomes. III. Molecular structure of the polyene antibiotic-cholesterol complexes. Biochim Biophys Acta Biomembr. 1974; 339(1): 57-70. https://doi.org/10.1016/0005-2736(74)90332-0
  • [11] Heikkilå H, Stubb S. The prevalence of onychomycosis in Finland. Br J Dermatol. 1995; 133(5): 699-703. https://doi.org/10.1111/j.1365-2133.1995.tb02741.x
  • [12] Roseeuw D. Achilles foot screening project: preliminary results of patients screened by dermatologists. J Eur Acad Dermatol Venereol. 1999; 12: S6-9. https://doi.org/10.1016/S0926-9959(99)00053-7
  • [13] Rocha KA, Krawczyk-Santos AP, Andrade LM, de Souza LC, Marreto RN, Gratieri T, Taveira SF. Voriconazole loaded nanostructured lipid carriers (NLC) for drug delivery in deeper regions of the nail plate. Int J Pharm. 2017; 531(1): 292-298. https://doi.org/10.1016/j.ijpharm.2017.08.115
  • [14] Bseiso EA, Nasr M, Sammour OA, Abd El Gawad NA. Novel nail penetration enhancer containing vesicles “nPEVs” for treatment of onychomycosis. Drug Deliv. 2016; 23(8): 2813-2819. https://doi.org/10.3109/10717544.2015.1099059
  • [15] Kaur IP, Kakkar S. Topical delivery of antifungal agents. Expert Opin Drug Deliv. 2010; 7(11): 1303-1327. https://doi.org/10.1517/17425247.2010.525230
  • [16] Matsuda Y, Sugiura K, Hashimoto T, Ueda A, Konno Y, Tatsumi Y. Efficacy coefficients determined using nail permeability and antifungal activity in keratin-containing media are useful for predicting clinical efficacies of topical drugs for onychomycosis. PLoS One. 2016; 11(7): e0159661. https://doi.org/10.1371/journal.pone.0159661
  • [17] Hay R. Therapy of skin, hair and nail fungal infections. J Fungi. 2018; 4(3): 99. https://doi.org/10.3390/jof4030099
  • [18] Akhtar N, Sahu S, Pathak K. Antifungal potential of tolnaftate against Candida albicans in the treatment of onychomycosis: development of nail lacquer and ex vivo characterization. Pharm Biomed Res. 2016; 2(3): 1-12. https://doi.org/10.18869/acadpub.pbr.2.3.1
  • [19] Patley C, Sahu K, Chourasia R, Mansoori I, Shukla K, Garg A. Development And characterization of antifungal potential of topical emulgel formulation of tolnaftate. J Pharm Negat Results. 2023; 2185-2199. https://doi.org/10.47750/pnr.2023.14.S02.257
  • [20] Lal DK, Kumar B, Saeedan AS, Ansari MN. An overview of nanoemulgels for bioavailability enhancement in inflammatory conditions via topical delivery. Pharmaceutics. 2023; 15(4): 1187. https://doi.org/10.3390/pharmaceutics15041187
  • [21] Manian M, Jain P, Vora D, Banga AK. Formulation and evaluation of the in vitro performance of topical dermatological products containing diclofenac sodium. Pharmaceutics. 2022; 14(9): 1892. https://doi.org/10.3390/pharmaceutics14091892
  • [22] Singh Malik D, Mital N, Kaur G. Topical drug delivery systems: a patent review. Expert Opin Ther Pat. 2016; 26(2): 213-228. https://doi.org/10.1517/13543776.2016.1131267
  • [23] Ganeshpurkar A, Vaishya P, Jain S, Pandey V, Bansal D, Dubey N. Therapeutic round delivery of amphotericin B for effective treatment of Candida albicans induced dermal mycosis in rats via emulgel system: Formulation and evaluation. Indian J Dermatol. 2014; 59(4):369-374. https://doi.org/10.4103/0019-5154.135489
  • [24] Dandagi PM, Pandey P, Gadad AP, Mastiholimath VS. Formulation and evaluation of microemulsion based luliconazole topical delivery. Indian J Pharm Educ Res. 2020; 54(2): 293-301. https://doi.org/10.5530/ijper.54.2.34
  • [25] Varma VN, Maheshwari PV, Navya M, Reddy SC, Shivakumar HG, Gowda DV. Calcipotriol delivery into the skin as emulgel for effective permeation. Saudi Pharm J. 2014; 22(6): 591-599. https://doi.org/10.1016/j.jsps.2014.02.007
  • [26] Kavya M, Jacob AR, Nisha P. Pectin emulsions and emulgels: Bridging the correlation between rheology and microstructure. Food Hydrocoll. 2023; 143: 108868. https://doi.org/10.1016/j.foodhyd.2023.108868
  • [27] Butani D, Yewale C, Misra A. Topical Amphotericin B solid lipid nanoparticles: Design and development. Colloids Surf B. 2016; 139: 17-24. https://doi.org/10.1016/j.colsurfb.2015.07.032
  • [28] Zu Y, Sun W, Zhao X, Wang W, Li Y, Ge Y, Liu Y, Wang K. Preparation and characterization of amorphous amphotericin B nanoparticles for oral administration through liquid antisolvent precipitation. Eur J Pharm Sci. 2014; 53: 109-117. https://doi.org/10.1016/j.ejps.2013.12.005
  • [29] Giri Y, Habibullah S, Dixit PK, Mahalik G, Mohanty B, Behera A. Development of microemulgel formulations with varied permeation enhancers for transungual delivery of luliconazole in onychomycosis management. Colloids Surf B. 2024; 234: 113718. https://doi.org/10.1016/j.colsurfb.2023.113718
  • [30] Nasiri MI, Vora LK, Ershaid JA, Peng K, Tekko IA, Donnelly RF. Nanoemulsion-based dissolving microneedle arrays for enhanced intradermal and transdermal delivery. Drug Deliv Transl Res. 2022; 12(4): 881-896. https://doi.org/10.1007/s13346-021-01107-0
  • [31] Rawooth M, Habibullah SK, Qureshi D, Bharti D, Pal A, Mohanty B, Jarzębski M, Smułek W, Pal K. Effect of tamarind gum on the properties of phase-separated poly (vinyl alcohol) films. Polymers. 2022; 14(14): 2793. https://doi.org/10.3390/polym14142793
  • [32] Shinde U, Barkat Y, Singh K. Coloaded surface–modified PLGA nanoparticles for sustained ocular delivery of levofloxacin and flurbiprofen. J Pharm Innov. 2023; 18(4): 2348-2361. https://doi.org/10.1007/s12247-023-09796-5
  • [33] Srivastava N, Patel DK, Rai VK, Pal A, Yadav NP. Development of emulgel formulation for vaginal candidiasis: Pharmaceutical characterization, in vitro and in vivo evaluation. J Drug Deliv Sci Technol. 2018; 48: 490-498. https://doi.org/10.1016/j.jddst.2018.10.013
  • [34] Khan BA, Ullah S, Khan MK, Alshahrani SM, Braga VA. Formulation and evaluation of Ocimum basilicum-based emulgel for wound healing using animal model. Saudi Pharm J. 2020; 28(12): 1842-1850. https://doi.org/10.1016/j.jsps.2020.11.011
  • [35] Khullar R, Kumar D, Seth N, Saini S. Formulation and evaluation of mefenamic acid emulgel for topical delivery. Saudi Pharm J. 2012; 20(1): 63-67. https://doi.org/10.1016/j.jsps.2011.08.001
  • [36] Mahtab A, Anwar M, Mallick N, Naz Z, Jain GK, Ahmad FJ. Transungual delivery of ketoconazole nanoemulgel for the effective management of onychomycosis. AAPS PharmSciTech. 2016; 17: 1477-1490. https://doi.org/10.1208/s12249-016-0488-0
  • [37] Babu A, Sivakumar G, Das A, Bharti D, Qureshi D, Habibullah SK, Satheesan A, Mohanty B, Pal K, Maji S. Preparation and characterization of novel oleogels using jasmine floral wax and wheat germ oil for oral delivery of curcumin. ACS Omega. 2022; 7(34): 30125-30136. https://doi.org/10.1021/acsomega.2c03201
  • [38] Suman DK, Qureshi D, Behera H, Mallick SP, Habibullah SK, Mohanty B, Maji S, Anis A, Pal K. Gelatin and rice starch-based phase-separated hydrogel formulations for controlled drug delivery applications. Food, Medical, and Environmental Applications of Polysaccharides, Elsevier, New York, 2021, pp. 263-289.
  • [39] Bharti D, Kim D, Cerqueira MA, Mohanty B, Habibullah SK, Banerjee I, Pal K. Effect of biodegradable hydrophilic and hydrophobic emulsifiers on the oleogels containing sunflower wax and sunflower oil. Gels. 2021; 7(3): 133. https://doi.org/10.3390/gels7030133
  • [40] Ali F, Habibullah S, Mohanty B, Behera A, Giri Y, Nayak BS. Novel in-situ emulgel of acetazolamide for ocular drug delivery. J Appl Pharm Sci. 2023; 13(4): 127-135. https://doi.org/10.7324/JAPS.2023.53382
  • [41] Behera KP, Qureshi D, Mohanty B, Habibullah SK, Anis A, Shaikh H, Sarkar P, Verma S, Pal K. Bentonite increases the corneal permeation of the drug from the tamarind gum hydrogels. Food, Medical, and Environmental Applications of Polysaccharides. Elsevier, New York, 2021, pp. 291-322.
  • [42] Pal P, Thakur RS, Ray S, Mazumder B. Design and development of a safer non-invasive transungual drug delivery system for topical treatment of onychomycosis. Drug Dev Ind Pharm. 2015; 41(7): 1095-1099. https://doi.org/10.3109/03639045.2014.931966
  • [43] Ali F, Habibullah S, Giri Y, Behera A, Mohanty B. Formulation and evaluation of acetazolamide loaded in-situ gel for the treatment of glaucoma. J Pharm Res. 2023; 27(1): 74-85. https://doi.org/10.29228/jrp.291
There are 43 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Articles
Authors

Amulyaratna Behera This is me

Yashwant Giri This is me

Barsha Priyadarshini This is me

Gurudutta Pattnaik This is me

Biswaranjan Mohanty This is me

Sk Habibullah

B Jyotirmayee This is me

Publication Date
Submission Date January 25, 2024
Acceptance Date March 31, 2024
Published in Issue Year 2025 Volume: 29 Issue: 1

Cite

APA Behera, A., Giri, Y., Priyadarshini, B., Pattnaik, G., et al. (n.d.). Design and development of Amphotericin-B loaded transungual drug delivery system for the effective management of onychomycosis. Journal of Research in Pharmacy, 29(1), 210-221.
AMA Behera A, Giri Y, Priyadarshini B, Pattnaik G, Mohanty B, Habibullah S, Jyotirmayee B. Design and development of Amphotericin-B loaded transungual drug delivery system for the effective management of onychomycosis. J. Res. Pharm. 29(1):210-221.
Chicago Behera, Amulyaratna, Yashwant Giri, Barsha Priyadarshini, Gurudutta Pattnaik, Biswaranjan Mohanty, Sk Habibullah, and B Jyotirmayee. “Design and Development of Amphotericin-B Loaded Transungual Drug Delivery System for the Effective Management of Onychomycosis”. Journal of Research in Pharmacy 29, no. 1 n.d.: 210-21.
EndNote Behera A, Giri Y, Priyadarshini B, Pattnaik G, Mohanty B, Habibullah S, Jyotirmayee B Design and development of Amphotericin-B loaded transungual drug delivery system for the effective management of onychomycosis. Journal of Research in Pharmacy 29 1 210–221.
IEEE A. Behera, Y. Giri, B. Priyadarshini, G. Pattnaik, B. Mohanty, S. Habibullah, and B. Jyotirmayee, “Design and development of Amphotericin-B loaded transungual drug delivery system for the effective management of onychomycosis”, J. Res. Pharm., vol. 29, no. 1, pp. 210–221.
ISNAD Behera, Amulyaratna et al. “Design and Development of Amphotericin-B Loaded Transungual Drug Delivery System for the Effective Management of Onychomycosis”. Journal of Research in Pharmacy 29/1 (n.d.), 210-221.
JAMA Behera A, Giri Y, Priyadarshini B, Pattnaik G, Mohanty B, Habibullah S, Jyotirmayee B. Design and development of Amphotericin-B loaded transungual drug delivery system for the effective management of onychomycosis. J. Res. Pharm.;29:210–221.
MLA Behera, Amulyaratna et al. “Design and Development of Amphotericin-B Loaded Transungual Drug Delivery System for the Effective Management of Onychomycosis”. Journal of Research in Pharmacy, vol. 29, no. 1, pp. 210-21.
Vancouver Behera A, Giri Y, Priyadarshini B, Pattnaik G, Mohanty B, Habibullah S, Jyotirmayee B. Design and development of Amphotericin-B loaded transungual drug delivery system for the effective management of onychomycosis. J. Res. Pharm. 29(1):210-21.