title: Nanoemulsion gel-based topical delivery of an antifungal drug: in vitro activity and in vivo evaluation.
abstract: OBJECTIVE
  In this study, attempt has been focused to prepare a nanoemulsion (NE) gel for topical delivery of amphotericin B (AmB) for enhanced as well as sustained skin permeation, in vitro antifungal activity and in vivo toxicity assessment.
  
  
  METHODS
  A series of NE were prepared using sefsol-218 oil, Tween 80 and Transcutol-P by slow spontaneous titration method. Carbopol gel (0.5% w/w) was prepared containing 0.1% w/w AmB. Furthermore, NE gel (AmB-NE gel) was characterized for size, charge, pH, rheological behavior, drug release profile, skin permeability, hemolytic studies and ex vivo rat skin interaction with rat skin using differential scanning calorimeter. The drug permeability and skin irritation ability were examined with confocal laser scanning microscopy and Draize test, respectively. The in vitro antifungal activity was investigated against three fungal strains using the well agar diffusion method. Histopathological assessment was performed in rats to investigate their toxicological potential.
  
  
  CONCLUSIONS
  The AmB-NE gel (18.09 ± 0.6 µg/cm(2)/h) and NE (15.74 ± 0.4 µg/cm(2)/h) demonstrated the highest skin percutaneous permeation flux rate as compared to drug solution (4.59 ± 0.01 µg/cm(2)/h) suggesting better alternative to painful and nephrotoxic intravenous administration. Hemolytic and histopathological results revealed safe delivery of the drug. Based on combined results, NE and AmB-NE gel could be considered as an efficient, stable and safe carrier for enhanced and sustained topical delivery for AmB in local skin fungal infection.
  
  
  CONCLUSIONS
  Topical delivery of AmB is suitable delivery system in NE gel carrier for skin fungal infection.
authors.affiliation: a Department of Pharmaceutical Sciences , Birla Institute of Technology , Mesra, Ranchi , Jharkhand , India .
authors.forename: Afzal
authors.initials: A
authors.lastname: Hussain
authors.affiliation: b Department of Pharmacokinetic and Statistics , Fortis Clinical Research Ltd. , Faridabad , Haryana , India .
authors.forename: Abdus
authors.initials: A
authors.lastname: Samad
authors.affiliation: a Department of Pharmaceutical Sciences , Birla Institute of Technology , Mesra, Ranchi , Jharkhand , India .
authors.forename: S K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: a Department of Pharmaceutical Sciences , Birla Institute of Technology , Mesra, Ranchi , Jharkhand , India .
authors.forename: M N
authors.initials: MN
authors.lastname: Ahsan
authors.affiliation: a Department of Pharmaceutical Sciences , Birla Institute of Technology , Mesra, Ranchi , Jharkhand , India .
authors.forename: M W
authors.initials: MW
authors.lastname: Haque
authors.affiliation: c Depatment of Pharmaceutical Science , HNB Garhwal University (A Central University) , Srinagar , Utterakhand , India , and.
authors.forename: A
authors.initials: A
authors.lastname: Faruk
authors.affiliation: d Department of Pharmaceutics, Faculty of Pharmacy , Jamia Hamdard University , New Delhi , India.
authors.forename: F J
authors.initials: FJ
authors.lastname: Ahmed
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000279:Administration, Cutaneous; D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D001230:Aspergillus / Q000187:drug effects / Q000254:growth & development; D002152:Calorimetry, Differential Scanning; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D052978:Disk Diffusion Antimicrobial Tests; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005260:Female; D005782:Gels; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D008297:Male; D018613:Microscopy, Confocal; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D017208:Rats, Wistar; D012212:Rheology; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000180:Acrylic Resins; D000935:Antifungal Agents; D004337:Drug Carriers; D004655:Emulsions; D005026:Ethylene Glycols; D005782:Gels; D008055:Lipids; D011108:Polymers; D011136:Polysorbates; D011409:Propylene Glycols; C584816:capryol propylene glycol monocaprylate; C006912:carboxypolymethylene; D000666:Amphotericin B; C010111:carbitol
keywords: Amphotericin B; gel; nanoemulsion; nephrotoxicity; topical delivery