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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Novel Luliconazole Spanlastic Nanocarriers: Development and Characterisation

Author(s): Shirleen Miriam Marques, Dikshita Ullas Chavan, Prashant Jivaji Bhide, Madhusudan Joshi, Lalit Kumar* and Rupesh Kalidas Shirodkar*

Volume 20, Issue 6, 2023

Published on: 21 July, 2022

Page: [792 - 806] Pages: 15

DOI: 10.2174/1567201819666220516155048

Price: $65

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Abstract

Background: The formulation of spanlastic vesicles of luliconazole can be used to overcome its poor skin permeation and improve its antifungal efficacy.

Objective: In this study, we aimed to enhance the dermal delivery of luliconazole, an antifungal drug, through spanlastic vesicles.

Methods: A 23 regular factorial design was employed, using the Design Expert® software for optimization. The independent variables chosen were Span: Edge activator ratio, type of edge activator, and sonication intensity and their effect on the dependent variables, i.e., entrapment efficiency, particle size, and percentage of drug release after 8h were determined. Spanlastics were formulated by ethanol injection method using Tween 80 as an edge activator.

Results: Spanlastics were found to possess sizes in the nano range with entrapment efficiencies between 77 - 88% with optimum zeta potential and polydispersity index indicating a stable formulation. Differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared studies revealed complete encapsulation of the drug within the elastic carriers. The optimized spanlastic formulation was further incorporated into a gel base and was found to be sufficiently viscous, spreadable, homogenous, showed a prolonged release for up to 8h and was also found to be non-irritant. The in-vitro permeation study revealed that the flux value obtained for luliconazole entrapped in the vesicular spanlastics (0.2292 mg/cm2.h) was also found to be higher than that of the marketed (0.1302 mg/cm2.h) and conventional gel (0.1122 mg/cm2.h). The optimized gel formulation was also evaluated for its antimycotic activity. Moreover, the optimized gel formulation also possessed a greater antimycotic activity against Candida albicans. The spanlastics loaded hydrogel formulation was found to have a greater zone of inhibition in comparison to the marketed formulation, thus proving to have optimum antifungal activity against Candida albicans.

Conclusion: Collectively, the results revealed that spanlastics could be a potential nanocarrier for wellcontrolled delivery and for targeting deeper skin layers, thus providing new opportunities for dermal treatment.

Keywords: Spanlastics, luliconazole, antifungal, edge activator, dermal drug delivery, factorial design.

Graphical Abstract

[1]
Bajpai, V.K.; Khan, I.; Shukla, S.; Kumar, P.; Rather, I.A.; Park, Y.; Huh, Y.S.; Han, Y.K. Invasive fungal infections and their epidemiology: Measures in the clinical scenario. Biotechnol. Bioprocess Eng., 2019, 24(3), 436-444.
[http://dx.doi.org/10.1007/s12257-018-0477-0]
[2]
Teklebirhan, G.; Bitew, A. Prevalence of dermatophytic infection and the spectrum of dermatophytes in patients attending a tertiary hospital in Addis Ababa, Ethiopia. Int. J. Microbiol., 2015, 2015, 653419.
[http://dx.doi.org/10.1155/2015/653419] [PMID: 26448763]
[3]
Kaur, I.P.; Kakkar, S. Topical delivery of antifungal agents. Expert Opin. Drug Deliv., 2010, 7(11), 1303-1327.
[http://dx.doi.org/10.1517/17425247.2010.525230] [PMID: 20961206]
[4]
Kaur, M.; Singh, K.; Jain, S.K. Luliconazole vesicular based gel formulations for its enhanced topical delivery. J. Liposome Res., 2020, 30(4), 388-406.
[http://dx.doi.org/10.1080/08982104.2019.1682602] [PMID: 31631734]
[5]
Kumar, M.; Shanthi, N.; Mahato, A.K.; Soni, S.; Rajnikanth, P.S. Preparation of luliconazole nanocrystals loaded hydrogel for improvement of dissolution and antifungal activity. Heliyon, 2019, 5(5), e01688.
[http://dx.doi.org/10.1016/j.heliyon.2019.e01688] [PMID: 31193099]
[6]
Kansagra, H.; Mallick, S. Microemulsion-based antifungal gel of luliconazole for dermatophytes infections: Formulation, characterization and efficacy studies. J. Pharm. Investig., 2015, 46(1), 21-28.
[http://dx.doi.org/10.1007/s40005-015-0209-9]
[7]
Kapileshwari, G.R.; Barve, A.R.; Kumar, L.; Bhide, P.J.; Joshi, M.; Shirodkar, R.K. Novel drug delivery system of luliconazole-formulation and characterisation. J. Drug Deliv. Sci. Technol., 2020, 55, 101302.
[http://dx.doi.org/10.1016/j.jddst.2019.101302]
[8]
Baghel, S.; Nair, V.S.; Pirani, A.; Sravani, A.B.; Bhemisetty, B.; Ananthamurthy, K.; Aranjani, J.M.; Lewis, S.A. Luliconazole-loaded nanostructured lipid carriers for topical treatment of superficial Tinea infections. Dermatol. Ther., 2020, 33(6), e13959.
[http://dx.doi.org/10.1111/dth.13959] [PMID: 32618400]
[9]
Dave, V.; Bhardwaj, N.; Gupta, N.; Tak, K. Herbal ethosomal gel containing luliconazole for productive relevance in the field of biomedicine. 3 Biotech, 2020, 10, 97.
[10]
Kakkar, S.; Kaur, I.P. Spanlastics--a novel nanovesicular carrier system for ocular delivery. Int. J. Pharm., 2011, 413(1-2), 202-210.
[http://dx.doi.org/10.1016/j.ijpharm.2011.04.027] [PMID: 21540093]
[11]
Mahale, N.B.; Thakkar, P.D.; Mali, R.G.; Walunj, D.R.; Chaudhari, S.R. Niosomes: Novel sustained release nonionic stable vesicular systems--an overview. Adv. Colloid Interface Sci., 2012, 183-184, 46-54.
[http://dx.doi.org/10.1016/j.cis.2012.08.002] [PMID: 22947187]
[12]
Kumar, G.P.; Rajeshwarrao, P. Nonionic surfactant vesicular systems for effective drug delivery-an overview. Acta Pharm. Sin. B, 2011, 1(4), 208-219.
[http://dx.doi.org/10.1016/j.apsb.2011.09.002]
[13]
Yu, L.X.; Amidon, G.; Khan, M.A.; Hoag, S.W.; Polli, J.; Raju, G.K.; Woodcock, J. Understanding pharmaceutical quality by design. AAPS J., 2014, 16(4), 771-783.
[http://dx.doi.org/10.1208/s12248-014-9598-3] [PMID: 24854893]
[14]
Kakkar, S.; Kaur, I.P. A novel nanovesicular carrier system to deliver drug topically. Pharm. Dev. Technol., 2013, 18(3), 673-685.
[http://dx.doi.org/10.3109/10837450.2012.685655] [PMID: 22612232]
[15]
Singh, S.; Verma, D.; Mirza, M.A.; Mukharjee, A.; Dudeja, M.; Anwer, M.K.; Sultana, Y.; Talegaonkar, S.; Iqbal, Z. Development and optimization of ketoconazole loaded nano-transfersomal gel for vaginal delivery using Box-Behnken design: In vitro, ex vivo characterization and antimicrobial evaluation. J. Drug Deliv. Sci. Technol., 2017, 39, 95-103.
[http://dx.doi.org/10.1016/j.jddst.2017.03.007]
[16]
Fernandes, A.V.; Pydi, C.R.; Verma, R.; Jose, J.; Kumar, L. Design, preparation and in vitro characterizations of fluconazole loaded nanostructured lipid carriers. Braz. J. Pharm. Sci., 2020, 56, e18069.
[http://dx.doi.org/10.1590/s2175-97902019000318069]
[17]
Ashraf, O.; Nasr, M.; Nebsen, M.; Said, A.M.A.; Sammour, O. In vitro stabilization and in vivo improvement of ocular pharmacokinetics of the multi-therapeutic agent baicalin: Delineating the most suitable vesicular systems. Int. J. Pharm., 2018, 539(1-2), 83-94.
[http://dx.doi.org/10.1016/j.ijpharm.2018.01.041] [PMID: 29374518]
[18]
Tawfeek, H.M.; Abdellatif, A.A.H.; Abdel-Aleem, J.A.; Hassan, Y.A.; Fathalla, D. Transfersomal gel nanocarriers for enhancement the permeation of lornoxicam. J. Drug Deliv. Sci. Technol., 2020, 56, 101540.
[http://dx.doi.org/10.1016/j.jddst.2020.101540]
[19]
Elsherif, N.I.; Shamma, R.N.; Abdelbary, G. Terbinafine hydrochloride Trans-ungual delivery via nanovesicular systems: In vitro characterization and ex vivo evaluation. AAPS PharmSciTech, 2017, 18(2), 551-562.
[http://dx.doi.org/10.1208/s12249-016-0528-9] [PMID: 27138036]
[20]
Abbas, H.; Kamel, R.; El-Sayed, N. Dermal anti-oxidant, anti-inflammatory and anti-aging effects of Compritol ATO-based Resveratrol colloidal carriers prepared using mixed surfactants. Int. J. Pharm., 2018, 541(1-2), 37-47.
[http://dx.doi.org/10.1016/j.ijpharm.2018.01.054] [PMID: 29458209]
[21]
Ibrahim, T.M.; Abdallah, M.H.; El-Megrab, N.A.; El-Nahas, H.M. Transdermal ethosomal gel nanocarriers; a promising strategy for enhancement of anti-hypertensive effect of carvedilol. J. Liposome Res., 2019, 29(3), 215-228.
[http://dx.doi.org/10.1080/08982104.2018.1529793] [PMID: 30272506]
[22]
Wang, Z.; Mu, H.J.; Zhang, X.M.; Ma, P.K.; Lian, S.N.; Zhang, F.P.; Chu, S.Y.; Zhang, W.W.; Wang, A.P.; Wang, W.Y.; Sun, K.X. Lower irritation microemulsion-based rotigotine gel: Formulation optimization and in vitro and in vivo studies. Int. J. Nanomedicine, 2015, 10, 633-644.
[PMID: 25609965]
[23]
Mekonnen, A.; Tesfaye, S.; Christos, S.G.; Dires, K.; Zenebe, T.; Zegeye, N.; Shiferaw, Y.; Lulekal, E. Evaluation of skin irritation and acute and subacute oral toxicity of Lavandula angustifolia essential oils in rabbit and mice. J. Toxicol., 2019, 2019, 5979546.
[http://dx.doi.org/10.1155/2019/5979546] [PMID: 30833968]
[24]
ElMeshad, A.N.; Mohsen, A.M. Enhanced corneal permeation and antimycotic activity of itraconazole against Candida albicansvia a novel nanosystem vesicle. Drug Deliv., 2016, 23(7), 2115-2123.
[http://dx.doi.org/10.3109/10717544.2014.942811] [PMID: 25080226]
[25]
Fahmy, A.M.; El-Setouhy, D.A.; Habib, B.A.; Tayel, S.A. Enhancement of transdermal delivery of haloperidol via spanlastic dispersions: Entrapment efficiency vs. particle size. AAPS PharmSciTech, 2019, 20(3), 95.
[http://dx.doi.org/10.1208/s12249-019-1306-2] [PMID: 30694404]
[26]
Tayel, S.A.; El-Nabarawi, M.A.; Tadros, M.I.; Abd-Elsalam, W.H. Duodenum-triggered delivery of pravastatin sodium via enteric surface-coated nanovesicular spanlastic dispersions: Development, characterization and pharmacokinetic assessments. Int. J. Pharm., 2015, 483(1-2), 77-88.
[http://dx.doi.org/10.1016/j.ijpharm.2015.02.012] [PMID: 25666025]
[27]
Abdelrahman, F.E.; Elsayed, I.; Gad, M.K.; Elshafeey, A.H.; Mohamed, M.I. Response surface optimization, ex vivo and in vivo investigation of nasal spanlastics for bioavailability enhancement and brain targeting of risperidone. Int. J. Pharm., 2017, 530(1-2), 1-11.
[http://dx.doi.org/10.1016/j.ijpharm.2017.07.050] [PMID: 28733244]
[28]
Elmowafy, E.; El-Gogary, R.I.; Ragai, M.H.; Nasr, M. Novel antipsoriatic fluidized spanlastic nanovesicles: In vitro physicochemical characterization, ex vivo cutaneous retention and exploratory clinical therapeutic efficacy. Int. J. Pharm., 2019, 568, 118556.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118556] [PMID: 31348982]
[29]
Shojaeiarani, J.; Bajwa, D.; Holt, G. Sonication amplitude and processing time influence the cellulose nanocrystals morphology and dispersion. Nanocomposites, 2020, 6(1), 41-46.
[http://dx.doi.org/10.1080/20550324.2019.1710974]
[30]
Rao, Y.; Zheng, F.; Zhang, X.; Gao, J.; Liang, W. In vitro percutaneous permeation and skin accumulation of finasteride using vesicular ethosomal carriers. AAPS PharmSciTech, 2008, 9(3), 860-865.
[http://dx.doi.org/10.1208/s12249-008-9124-y] [PMID: 18649143]
[31]
Dubey, V.; Mishra, D.; Dutta, T.; Nahar, M.; Saraf, D.K.; Jain, N.K. Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes. J. Control. Release, 2007, 123(2), 148-154.
[http://dx.doi.org/10.1016/j.jconrel.2007.08.005] [PMID: 17884226]
[32]
Abdelbary, G.; El-Gendy, N. Niosome-encapsulated gentamicin for ophthalmic controlled delivery. AAPS PharmSciTech, 2008, 9(3), 740-747.
[http://dx.doi.org/10.1208/s12249-008-9105-1] [PMID: 18563578]
[33]
Chen, J.; Lu, W.L.; Gu, W.; Lu, S.S.; Chen, Z.P.; Cai, B.C. Skin permeation behavior of elastic liposomes: Role of formulation ingredients. Expert Opin. Drug Deliv., 2013, 10(6), 845-856.
[http://dx.doi.org/10.1517/17425247.2013.779252] [PMID: 23550630]
[34]
Apsara, S.; Opatha, T.; Titapiwatanakun, V.; Chutoprapat, R. Transferosomes: A promising nanoencapsulation technique for transdermal drug deivery. Pharmaceutics, 2020, 12(9), 855.
[http://dx.doi.org/10.3390/pharmaceutics12090855]
[35]
Sallam, N.M.; Sanad, R.A.B.; Ahmed, M.M.; Khafagy, E.L.S.; Ghorab, M.; Gad, S. Impact of the mucoadhesive lyophilized wafer loaded with novel carvedilol nano-spanlastics on biochemical markers in the heart of spontaneously hypertensive rat models. Drug Deliv. Transl. Res., 2021, 11(3), 1009-1036.
[http://dx.doi.org/10.1007/s13346-020-00814-4] [PMID: 32607938]
[36]
Ruckmani, K.; Sankar, V. Formulation and optimization of Zidovudine niosomes. AAPS PharmSciTech, 2010, 11(3), 1119-1127.
[http://dx.doi.org/10.1208/s12249-010-9480-2] [PMID: 20635228]
[37]
Tran, T.T.; Tran, P.H.; Nguyen, M.N.U.; Tran, K.T.M.; Pham, M.N.; Tran, P.C.; Vo, T.V. Amorphous isradipine nanosuspension by the sonoprecipitation method. Int. J. Pharm., 2014, 474(1-2), 146-150.
[http://dx.doi.org/10.1016/j.ijpharm.2014.08.017] [PMID: 25138256]
[38]
Kaur, I.P.; Rana, C.; Singh, M.; Bhushan, S.; Singh, H.; Kakkar, S. Development and evaluation of novel surfactant-based elastic vesicular system for ocular delivery of fluconazole. J. Ocul. Pharmacol. Ther., 2012, 28(5), 484-496.
[http://dx.doi.org/10.1089/jop.2011.0176] [PMID: 22694593]
[39]
Basha, M.; Abd El-Alim, S.H.; Shamma, R.N.; Awad, G.E.A. Design and optimization of surfactant-based nanovesicles for ocular delivery of Clotrimazole. J. Liposome Res., 2013, 23(3), 203-210.
[http://dx.doi.org/10.3109/08982104.2013.788025] [PMID: 23607316]
[40]
Agrawal, R.; Sandhu, S.K.; Sharma, I.; Kaur, I.P. Development and evaluation of curcumin-loaded elastic vesicles as an effective topical anti-inflammatory formulation. AAPS PharmSciTech, 2015, 16(2), 364-374.
[http://dx.doi.org/10.1208/s12249-014-0232-6] [PMID: 25319056]
[41]
Ioele, G.; Tavano, L.; De Luca, M.; Ragno, G.; Picci, N.; Muzzalupo, R. Photostability and ex-vivo permeation studies on diclofenac in topical niosomal formulations. Int. J. Pharm., 2015, 494(1), 490-497.
[http://dx.doi.org/10.1016/j.ijpharm.2015.08.053] [PMID: 26307262]

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