Generic placeholder image

Recent Advances in Anti-Infective Drug Discovery

Editor-in-Chief

ISSN (Print): 2772-4344
ISSN (Online): 2772-4352

Research Article

Oleic Acid Vesicles as a New Approach for Transdermal Delivery of Econazole Nitrate: Development, Characterization, and In-vivo Evaluation in Wistar Rats

Author(s): Shivani Verma and Puneet Utreja*

Volume 16, Issue 1, 2021

Published on: 10 November, 2020

Page: [30 - 49] Pages: 20

DOI: 10.2174/1574891X15999201110212725

Price: $65

Abstract

Background: Cutaneous candidiasis is a deep-seated skin fungal infection that is most commonly observed in immunocompromised patients. This fungal infection is conventionally treated with various formulations like gels and creams which are having different side effects and the least therapeutic efficacy. Hence, it becomes necessary to develop a novel carrier system for the treatment of this deep-seated skin fungal infection. Econazole nitrate is the most widely used antifungal for the treatment of cutaneous candidiasis and many patents have been granted by various pharmaceutical scientists around the globe related to nanocarrier systems for transdermal delivery of antifungal drugs like econazole nitrate (ECN) therefore, we developed and evaluated econazole nitrate loaded oleic acid vesicles in the present research work for treatment of cutaneous candidiasis through transdermal route.

Methods: Econazole nitrate loaded oleic acid vesicles were prepared by thin-film hydration and characterized for drug entrapment, vesicle size, zeta potential, polydispersity index (PDI), Fourier Transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. Furthermore, the oleic acid vesicular gel was evaluated for ex-vivo skin permeation/retention and in-vitro and in-vivo antifungal activity in Wistar rats.

Results: Econazole nitrate loaded oleic acid vesicles showed high encapsulation of drug (74.76 ± 3.0%), acceptable size (373.4 ± 2.9 nm), and colloidal characteristics (PDI = 0.231 ± 0.078, and zeta potential = -13.27 ± 0.80 mV). The oleic acid vesicular gel showed high skin permeation (Transdermal flux = 61.98 ± 2.45 μg/cm2/h), skin retention (35.90 ± 2.06%), in-vitro, and in-vivo antifungal activity compared to marketed cream (Ecoderm R) of econazole nitrate for a prolonged time (4 days).

Conclusion: Developed econazole nitrate loaded oleic acid vesicles could be used effectively in the treatment of cutaneous candidiasis with minimization of side effects of econazole nitrate with increased therapeutic efficacy.

Keywords: Colloidal, cutaneous, econazole nitrate, oleic acid vesicles, skin permeation, transdermal, zeta potential.

Erratum In:
Corrigendum to: Oleic Acid Vesicles as a New Approach for Transdermal Delivery of Econazole Nitrate: Development, Characterization, and In-vivo Evaluation in Wistar Rats

Graphical Abstract
[1]
Cosco D, Celia C, Cilurzo F, Trapasso E, Paolino D, et al. Colloidal carriers for the enhanced delivery through the skin. Expert Opin Drug Deliv 2008; 5(7): 737-55.
[http://dx.doi.org/10.1517/17425247.5.7.737] [PMID: 18590459]
[2]
Singh D, Pradhan M, Nag M, et al. Vesicular system: Versatile carrier for transdermal delivery of bioactives. Artif Cells Nanomed Biotechnol 2015; 43(4): 282-90.
[http://dx.doi.org/10.3109/21691401.2014.883401] [PMID: 24564350]
[3]
Sinico C, Fadda AM. Vesicular carriers for dermal drug delivery. Expert Opin Drug Deliv 2009; 6(8): 813-25.
[http://dx.doi.org/10.1517/17425240903071029] [PMID: 19569979]
[4]
Cevc G. Lipid vesicles and other colloids as drug carriers on the skin. Adv Drug Deliv Rev 2004; 56(5): 675-711.
[http://dx.doi.org/10.1016/j.addr.2003.10.028] [PMID: 15019752]
[5]
Cevc G. Lipid vesicles and other colloids as drug carriers on the skin. Adv Drug Deliv Rev 2004; 56(5): 675-711.
[http://dx.doi.org/10.1016/j.addr.2003.10.028] [PMID: 15019752]
[6]
Kavian Z, Alavizadeh SH, Golmohamadzadeh S, Badiee A, Khamesipour A, Jaafari MR, et al. Development of topical liposomes containing miltefosine for the treatment of Leishmania major infection in susceptible BALB/c mice. Acta Trop 2019; 196: 142-9.
[http://dx.doi.org/10.1016/j.actatropica.2019.05.018] [PMID: 31103698]
[7]
Jain SK, Gupta Y, Jain A, Rai K, et al. Enhanced transdermal delivery of acyclovir sodium via elastic liposomes. Drug Deliv 2008; 15(3): 141-7.
[http://dx.doi.org/10.1080/10717540801952407] [PMID: 18379926]
[8]
El-Ridy MS, Yehia SA, Mohsen AM, El-Awdan SA, Darwish AB, et al. Formulation of Niosomal Gel for Enhanced Transdermal Lornoxicam Delivery: In-Vitro and In-Vivo Evaluation. Curr Drug Deliv 2018; 15(1): 122-33.
[http://dx.doi.org/10.2174/1567201814666170224141548] [PMID: 28240177]
[9]
da Silva CL, Del Ciampo JO, Rossetti FC, Bentley MV, Pierre MB, et al. Improved in vitro and in vivo cutaneous delivery of protoporphyrin IX from PLGA-based nanoparticles. Photochem Photobiol 2013; 89(5): 1176-84.
[http://dx.doi.org/10.1111/php.12121] [PMID: 23800045]
[10]
Kurakula M, Ahmed OA, Fahmy UA, Ahmed TA, et al. Solid lipid nanoparticles for transdermal delivery of avanafil: optimization, formulation, in-vitro and ex-vivo studies. J Liposome Res 2016; 26(4): 288-96.
[http://dx.doi.org/10.3109/08982104.2015.1117490] [PMID: 26784833]
[11]
Shakeel F, Baboota S, Ahuja A, Ali J, Aqil M, Shafiq S, et al. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech 2007; 8(4): E104.
[http://dx.doi.org/10.1208/pt0804104] [PMID: 18181525]
[12]
Bahl D, Daftardar S, Devi Bachu R, Boddu SHS, Altorok N, Kahaleh B, et al. Evaluation of topical econazole nitrate formulations with potential for treating Raynaud’s phenomenon. Pharm Dev Technol 2019; 24(6): 689-99.
[http://dx.doi.org/10.1080/10837450.2019.1578371] [PMID: 30712434]
[13]
Daily AD, Kramer KJ, Rex IH, Thorne EG, et al. Econazole nitrate (Spectazole) cream, 1 percent: a topical agent for the treatment of tinea pedis. Cutis 1985; 35(3): 278-80.
[PMID: 3979113]
[14]
Pitman SK, Drew RH, Perfect JR. Addressing current medical needs in invasive fungal infection prevention and treatment with new antifungal agents, strategies and formulations. Expert Opin Emerg Drugs 2011; 16(3): 559-86.
[http://dx.doi.org/10.1517/14728214.2011.607811] [PMID: 21846302]
[15]
Na YG, Huh HW, Kim MK, et al. Development and evaluation of a film-forming system hybridized with econazole-loaded nanostructured lipid carriers for enhanced antifungal activity against dermatophytes. Acta Biomater 2020; 101: 507-18.
[http://dx.doi.org/10.1016/j.actbio.2019.10.024] [PMID: 31629894]
[16]
da Silva ER, de Freitas ZM, Gitirana LdeB, Ricci-Júnior E, et al. Improving the topical delivery of zinc phthalocyanine using oleic acid as a penetration enhancer: in vitro permeation and retention. Drug Dev Ind Pharm 2011; 37(5): 569-75.
[http://dx.doi.org/10.3109/03639045.2010.529144] [PMID: 21128702]
[17]
Kumar L, Verma S, Kumar S, Prasad DN, Jain AK, et al. Fatty acid vesicles acting as expanding horizon for transdermal delivery. Artif Cells Nanomed Biotechnol 2017; 45(2): 251-60.
[http://dx.doi.org/10.3109/21691401.2016.1146729] [PMID: 26890090]
[18]
Murakami M, Yoshikawa H, Takada K, Muranishi S, et al. Effect of oleic Acid vesicles on intestinal absorption of carboxyfluorescein in rats. Pharm Res 1986; 3(1): 35-40.
[http://dx.doi.org/10.1023/A:1016368714631] [PMID: 24271354]
[19]
Kumar P, Singh SK, Handa V, Kathuria H, et al. Oleic Acid Nanovesicles of Minoxidil for Enhanced Follicular Delivery. Medicines 2018; 5(3): E103.
[http://dx.doi.org/10.3390/medicines5030103] [PMID: 30223446]
[20]
Zakir F, Vaidya B, Goyal AK, Malik B, Vyas SP, et al. Development and characterization of oleic acid vesicles for the topical delivery of fluconazole. Drug Deliv 2010; 17(4): 238-48.
[http://dx.doi.org/10.3109/10717541003680981] [PMID: 20235758]
[21]
Mittal R, Sharma A, Arora S. Ufasomes mediated cutaneous delivery of dexamethasone: formulation and evaluation of anti-inflammatory activity by carrageenin-induced rat paw edema model. J Pharm 2013; 2013: 680580.
[http://dx.doi.org/10.1155/2013/680580] [PMID: 26555990]
[22]
Tan HW, Misran M. Polysaccharide-anchored fatty acid liposome. Int J Pharm 2013; 441(1-2): 414-23.
[http://dx.doi.org/10.1016/j.ijpharm.2012.11.013] [PMID: 23174410]
[23]
Ahmed TA. Preparation of transfersomes encapsulating sildenafil aimed for transdermal drug delivery: Plackett-Burman design and characterization. J Liposome Res 2015; 25(1): 1-10.
[http://dx.doi.org/10.3109/08982104.2014.950276] [PMID: 25148294]
[24]
Ali MFM, Salem HF, Abdelmohsen HF, Attia SK, et al. Preparation and clinical evaluation of nano-transferosomes for treatment of erectile dysfunction. Drug Des Devel Ther 2015; 9: 2431-47.
[PMID: 25995616]
[25]
Gupta V, Barupal AK, Ramteke S. Formulation Development and in vitro Characterization of Proliposomes for Topical Delivery of Aceclofenac. Indian J Pharm Sci 2008; 70(6): 768-75.
[http://dx.doi.org/10.4103/0250-474X.49119] [PMID: 21369438]
[26]
Khan S, Jain P, Jain S, Jain R, Bhargava S, Jain A, et al. Topical Delivery of Erythromycin Through Cubosomes for Acne. Pharm Nanotechnol 2018; 6(1): 38-47.
[http://dx.doi.org/10.2174/2211738506666180209100222] [PMID: 29424323]
[27]
Omar MM, Hasan OA, El Sisi AM. Preparation and optimization of lidocaine transferosomal gel containing permeation enhancers: a promising approach for enhancement of skin permeation. Int J Nanomedicine 2019; 14: 1551-62.
[http://dx.doi.org/10.2147/IJN.S201356] [PMID: 30880964]
[28]
Mohamed MI. Optimization of chlorphenesin emulgel formulation. AAPS J 2004; 6(3): e26.
[http://dx.doi.org/10.1208/aapsj060326] [PMID: 15760111]
[29]
Omar MM, Hasan OA, El Sisi AM. Preparation and optimization of lidocaine transferosomal gel containing permeation enhancers: a promising approach for enhancement of skin permeation. Int J Nanomedicine 2019; 14: 1551-62.
[http://dx.doi.org/10.2147/IJN.S201356] [PMID: 30880964]
[30]
Ahad A, Al-Saleh AA, Al-Mohizea AM, et al. Formulation and characterization of novel soft nanovesicles for enhanced transdermal delivery of eprosartan mesylate. Saudi Pharm J 2017; 25(7): 1040-6.
[http://dx.doi.org/10.1016/j.jsps.2017.01.006] [PMID: 29158713]
[31]
Nava G, Piñón E, Mendoza L, Mendoza N, Quintanar D, Ganem A, et al. Formulation and in Vitro, ex Vivo and in Vivo Evaluation of Elastic Liposomes for Transdermal Delivery of Ketorolac Tromethamine. Pharmaceutics 2011; 3(4): 954-70.
[http://dx.doi.org/10.3390/pharmaceutics3040954] [PMID: 24309316]
[32]
Ali AM, Al-Remawi MM. Freeze Dried Quetiapine-Nicotinamide Binary Solid Dispersions: A New Strategy for Improving Physicochemical Properties and Ex Vivo Diffusion. J Pharm 2016; 2016: 2126056.
[http://dx.doi.org/10.1155/2016/2126056] [PMID: 28042494]
[33]
Kaur P, Garg V, Bawa P, et al. Formulation; systematic optimization; in vitro; ex vivo; and stability assessment of transethosome based gel of curcumin. Asi J Pharm Clin Res 2018; 11(2): 41-7.
[http://dx.doi.org/10.22159/ajpcr.2018.v11s2.28563]
[34]
Gupta M, Goyal AK, Paliwal SR, et al. Development and characterization of effective topical liposomal system for localized treatment of cutaneous candidiasis. J Liposome Res 2010; 20(4): 341-50.
[http://dx.doi.org/10.3109/08982101003596125] [PMID: 20163329]
[35]
Raja J, Muralidharan S, Parasuraman S. In Vitro and in Vivo evaluation of microspheres loaded topical gel delivery system of ketoconazole in male rats against Candida Glabrata. J Pharm Sci Res 2014; 6: 376-81.
[36]
Akhtar N, Pathak K. Cavamax W7 composite ethosomal gel of clotrimazole for improved topical delivery: development and comparison with ethosomal gel. AAPS PharmSciTech 2012; 13(1): 344-55.
[http://dx.doi.org/10.1208/s12249-012-9754-y] [PMID: 22282041]
[37]
Maebashi K, Itoyama T, Uchida K, Suegara N, Yamaguchi H, et al. A novel model of cutaneous candidiasis produced in prednisolone-treated guinea-pigs. J Med Vet Mycol 1994; 32(5): 349-59.
[http://dx.doi.org/10.1080/02681219480000471] [PMID: 7844701]
[38]
Kumar L, Verma S, Jamwal S, Vaidya S, Vaidya B, et al. Polymeric microparticles-based formulation for the eradication of cutaneous candidiasis: development and characterization. Pharm Dev Technol 2014; 19(3): 318-25.
[http://dx.doi.org/10.3109/10837450.2013.778874] [PMID: 23560821]
[39]
Gupta M, Vyas SP. Development, characterization and in vivo assessment of effective lipidic nanoparticles for dermal delivery of fluconazole against cutaneous candidiasis. Chem Phys Lipids 2012; 165(4): 454-61.
[http://dx.doi.org/10.1016/j.chemphyslip.2012.01.006] [PMID: 22309657]
[40]
Popović G, Čakar M, Vučićević K, Vladimirov S, Agbaba D, et al. Comparison of HPTLC and HPLC for determination of econazole nitrate in topical dosage forms JPC - J Planar Chromat 2004; 17 (2 ): 109 -2 .
[http://dx.doi.org/10.1556/JPC.17.2004.2.5]
[41]
Kaur N, Garg R. Optimization and Evaluation of Oleic Acid Based Unsaturated Fatty Acid Liposomes Gel. J Bioequivalence Bioavailab 2017; 9: 424-9.
[42]
Ahad A, Al-Saleh AA, Al-Mohizea AM, et al. Formulation and characterization of Phospholipon 90 G and tween 80 based transfersomes for transdermal delivery of eprosartan mesylate. Pharm Dev Technol 2018; 23(8): 787-93.
[http://dx.doi.org/10.1080/10837450.2017.1330345] [PMID: 28504046]
[43]
El Zaafarany GM, Awad GA, Holayel SM, Mortada ND, et al. Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery. Int J Pharm 2010; 397(1-2): 164-72.
[http://dx.doi.org/10.1016/j.ijpharm.2010.06.034] [PMID: 20599487]
[44]
Jain S, Jain P, Umamaheshwari RB, Jain NK, et al. Transfersomes- a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation. Drug Dev Ind Pharm 2003; 29(9): 1013-26.
[http://dx.doi.org/10.1081/DDC-120025458] [PMID: 14606665]
[45]
Gajra B, Pandya SS, Singh S, Rabari HA, et al. Mucoadhesive hydrogel films of econazole nitrate: formulation and optimization using factorial design. Journal Drug Del 2014; 2014305863
[http://dx.doi.org/10.1155/2014/305863]
[46]
Malik DS, Kaur G. Exploring therapeutic potential of azelaic acid loaded NLCs for the treatment of acne vulgaris. J Drug Deliv Sci Technol 2020; 55: 101418.
[http://dx.doi.org/10.1016/j.jddst.2019.101418]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy