Optimized D-α-tocopherol polyethylene glycol succinate/phospholipid self-assembled mixed micelles: A promising lipid-based nanoplatform for augmenting the antifungal activity of fluconazole

Abstract Fluconazole (FLZ) is the most widely used antifungal agent for treating cutaneous candidiasis. Although oral FLZ has been proved to be effective, the incidence of side effects necessitates the development of an effective formulation that could surpass the pitfalls associated with systemic availability. Accordingly, this research aimed at developing a self-assembled mixed micelles topical delivery system to enhance the topical delivery of the drug. Self-assembled mixed micelles were developed using D-α-tocopheryl polyethylene glycol 1000 succinate and phospholipids and optimized using Box-Behnken design. The optimized formulation with minimized size was then tested in vivo for the antifungal activity against C. albicans in immunocompromised mice. Treatment with the optimized formulation led to decreased peripheral erythema as well as lesions due to fungal infection in comparison to raw FLZ loaded gel. Therefore, the developed formulation was found to be a promising vehicle for the treatment of cutaneous candidiasis.

[1]  Statement of retraction: Influence of various lipid core on characteristics of SLNs designed for topical delivery of fluconazole against cutaneous candidiasis. , 2022, Pharmaceutical development and technology.

[2]  N. Alhakamy,et al.  Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer , 2021, Frontiers in Pharmacology.

[3]  Jiang-nan Yu,et al.  Mixed micelles for enhanced oral bioavailability and hypolipidemic effect of liquiritin: preparation, in vitro and in vivo evaluation , 2021, Drug development and industrial pharmacy.

[4]  F. Caraci,et al.  Cytotoxic and Pro-Apoptotic Effects of a Sub-Toxic Concentration of Fluvastatin on OVCAR3 Ovarian Cancer Cells After its Optimized Formulation to Melittin Nano-Conjugates , 2021, Frontiers in Pharmacology.

[5]  B. Fries,et al.  Candidiasis and Mechanisms of Antifungal Resistance , 2020, Antibiotics.

[6]  O. Madkhali,et al.  Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation , 2020, Pharmaceutics.

[7]  S. M. Badr-Eldin,et al.  Investigating the potential of utilizing glycerosomes as a novel vesicular platform for enhancing intranasal delivery of lacidipine. , 2020, International journal of pharmaceutics.

[8]  Z. Binkhathlan,et al.  Antifungal efficacy of Itraconazole loaded PLGA-nanoparticles stabilized by vitamin-E TPGS: In vitro and ex vivo studies. , 2019, Journal of microbiological methods.

[9]  O. Ahmed,et al.  Optimized vinpocetine-loaded vitamin E D-α-tocopherol polyethylene glycol 1000 succinate-alpha lipoic acid micelles as a potential transdermal drug delivery system: in vitro and ex vivo studies , 2018, International journal of nanomedicine.

[10]  S. M. Badr-Eldin,et al.  Optimized Chitosan/Anion Polyelectrolyte Complex Based Inserts for Vaginal Delivery of Fluconazole: In Vitro/In Vivo Evaluation , 2018, Pharmaceutics.

[11]  B. Mishra,et al.  Design, optimization, characterization and in-vivo evaluation of Quercetin enveloped Soluplus®/P407 micelles in diabetes treatment , 2018, Artificial cells, nanomedicine, and biotechnology.

[12]  O. Ahmed,et al.  In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: formulation, characterization, and in vivo performance , 2018, International journal of nanomedicine.

[13]  A. Bressan,et al.  Cutaneous candidiasis caused by Candida albicans in a young non-immunosuppressed patient: an unusual presentation , 2018, International journal of immunopathology and pharmacology.

[14]  Wessam H. Abd-elsalam,et al.  Formulation and in vivo assessment of terconazole-loaded polymeric mixed micelles enriched with Cremophor EL as dual functioning mediator for augmenting physical stability and skin delivery , 2018, Drug delivery.

[15]  E. Bendas,et al.  Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: formulation and clinical study , 2017, Drug delivery.

[16]  B. Chudzik-Rząd,et al.  Mixed micelles as drug delivery nanocarriers , 2018 .

[17]  Chia-Yu Su,et al.  Development and Characterization of Lecithin-based Self-assembling Mixed Polymeric Micellar (saMPMs) Drug Delivery Systems for Curcumin , 2016, Scientific Reports.

[18]  P. Matricardi,et al.  Glycerosomes: Use of hydrogenated soy phosphatidylcholine mixture and its effect on vesicle features and diclofenac skin penetration. , 2016, International journal of pharmaceutics.

[19]  Mingyi Yao,et al.  Development and evaluation of vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate-mixed polymeric phospholipid micelles of berberine as an anticancer nanopharmaceutical , 2016, International journal of nanomedicine.

[20]  Gursharan Singh,et al.  Development of aprepitant loaded orally disintegrating films for enhanced pharmacokinetic performance. , 2016, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[21]  S. Ghanbarzadeh,et al.  The Effect of Particle Size on the Deposition of Solid Lipid Nanoparticles in Different Skin Layers: A Histological Study , 2016, Advanced pharmaceutical bulletin.

[22]  Zhenhai Zhang,et al.  TPGS/Phospholipids Mixed Micelles for Delivery of Icariside II to Multidrug-Resistant Breast Cancer , 2015, Integrative cancer therapies.

[23]  G. Galati,et al.  Rhodotorula mucilaginosa skin infection in a patient treated with sorafenib , 2015, Journal of the European Academy of Dermatology and Venereology : JEADV.

[24]  Shanshan Li,et al.  Antifungal efficacy of itraconazole-loaded TPGS-b-(PCL-ran-PGA) nanoparticles , 2015, International journal of nanomedicine.

[25]  Andrew Owen,et al.  The Application of Nanotechnology to Drug Delivery in Medicine , 2015 .

[26]  D. Kohli,et al.  Treatment of cutaneous candidiasis through fluconazole encapsulated cubosomes , 2014, Drug Delivery and Translational Research.

[27]  A. E. S. Abou El Ela,et al.  Formulation and evaluation of new long acting metoprolol tartrate ophthalmic gels , 2014, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[28]  Madhu Gupta,et al.  RETRACTED ARTICLE: Influence of various lipid core on characteristics of SLNs designed for topical delivery of fluconazole against cutaneous candidiasis , 2013, Pharmaceutical development and technology.

[29]  Walter J. Riker A Review of J , 2010 .

[30]  N. Shastri,et al.  DEVELOPMENT AND VALIDATION OF RP-HPLC AND UV METHODS OF ANALYSIS FOR FLUCONAZOLE IN PHARMACEUTICAL SOLID DOSAGE FORMS , 2009 .

[31]  H. Ellaithy,et al.  The development of Cutina lipogels and gel microemulsion for topical administration of fluconazole , 2008, AAPS PharmSciTech.

[32]  R. Barnes,et al.  Topical and oral treatments for fungal skin infections , 2006 .

[33]  Si-Shen Feng,et al.  PLGA/TPGS Nanoparticles for Controlled Release of Paclitaxel: Effects of the Emulsifier and Drug Loading Ratio , 2003, Pharmaceutical Research.

[34]  M. Fresno,et al.  Candida albicans infection enhances immunosuppression induced by cyclophosphamide by selective priming of suppressive myeloid progenitors for NO production. , 2002, Cellular immunology.

[35]  M. Martín,et al.  The use of fluconazole and itraconazole in the treatment of Candida albicans infections: a review. , 1999, The Journal of antimicrobial chemotherapy.

[36]  H. Yamaguchi,et al.  A novel model of cutaneous candidiasis produced in prednisolone-treated guinea-pigs. , 1994, Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology.

[37]  O. Welsh,et al.  Once‐weekly oral doses of fluconazole 150 mg in the treatment of tinea corporis/cruris and cutaneous candidiasis , 1992, Clinical and experimental dermatology.