Fabrication and Characterization of Novel Nanofibrous Scaffolds for the Controlled Delivery of Tolnaftate to Treat Dermatophytic Infections
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Date
2018
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FACULTY OF HEALTH SCIENCES SAM HIGGINBOTTOM UNIVERSITY OF AGRICULTURE, TECHNOLOGY AND SCIENCES (FORMERLY ALLAHABAD AGRICULTURAL INSTITUTE) ALLAHABAD 2018
Abstract
Filamentous dermatophytes are immensely mortifying and keratinophilic eukaryotes, infected
¼th of world’s community till date. In an opportunistic role they are extremely devastating, as
dermatophytes take advantage of a host with weakened immune system. Patients suffering from
AIDS, cancer, old age senescence, diabetes, cystic fibrosis become more vulnerable to
dermatophytosis. These pathogenic dermatophytes are keratinophilic fungi include species of
Microsporum, Trichophyton and Epidermophyton which secrete proteolytic enzyme and affect
keratin by making environment alkaline around at the site of action. The conventional remedial
in form of cream, powder, lotion and gels prove effective as prophylactic at a prelim phase. At
advanced and severe state of infection, these measures prove rather helpless due to some
shortcomings associated with their use as the drug releases immediately and before reaching the
pathogen site it interacts with healthy tissues also. The interaction may trigger on host’s immune
system, and create allergic symptoms like itching or burning sensations in the host. Herein, we
report fabrication of PEGylated nanofibrous scaffold, possessing enhanced localized antifungal
activity against dermatophytes through development of nanoconjugate (TOL-GN) from amalgam
of thiocarbamate derivative tolnaftate (TOL) and bioactive carbon allotrope graphene (GN),
loaded on Eudragit polymers (ERL100/ ERS100). The rationale behind fabrication of
nanofibrous scaffold was to synergize topical antifungal activity of TOL against pathogenic
dermatophytes. In this regard, balanced combination of biocompatible ERL100 and ERS100
were selected to provide better adhesion on site of dermatophytosis, ample absorption of
exudates during treatment and also customizing controlled drug release. Drug and polymers were
found to be compatible and stable to each other through FTIR, XRD and DSC/ TGA studies.
Surface topography analyzed that the scaffolds were regular, defect free, comprising distinct
pockets with nanoscaled diameter. Excellent swelling index and remarked hydrophilicity were
obtained which gratified essential benchmark for fabrication of nanofibrous scaffolds to alleviate
dermatophytosis. In vitro drug release followed kinetics of Korsermeyer- Peppas model,
suggested diffusion based mechanism from scafolds. Microdilution assay was carried out against
extremely devastating dermatophytes i.e. Trichophyton rubrum, Microsporum canis,
Microsporum gypseum and Microsporum fulvum. C3 nanofibers exhibited more prolong and
preeminent activity against T.rubrum than D3 nanofibers. In vivo activity on dermatophytic
swiss albino mice revealed superior antifungal activity of C3 nanofibers on successive 7 days of
application and offered biocompatible topical rostrum to tailor localized and controlled drug
delivery at the site of infection. The investigation offered futuristic potential usage of
nanoconjugate TOL- GN loaded polyacrylate nanofibers as dressing materials/ scaffolds for
effective management of dermatophytosis.
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