Luliconazole Loaded Electrospun Mucoadhesive Nanofiber: A Novel Nanoconstruct For The Treatment Of Vulvovaginal Candidiasis

Abstract

Vulvovaginal candidiasis primarily caused by the overgrowth of Candida albicans affecting women mainly in their reproductive ages. Main challenge is delivering the drug to the desirable site. Vagina is an intricate route for drug delivery due to hormonal activity, presence of microbiota and enzymes, change in pH, excessive secretion of vaginal fluid, and thickness of the vaginal tissue layer that catalyses with age, which alters the absorption and bioavailability of the drug. Conventional dosage forms exhibit poor biodistribution, limited effectiveness, undesirable effects, chemical degradation, clearance and lack of selectivity. To overcome the aforesaid challenges, necessitates a strategic formulation with improved therapeutic outcomes for eliminating and countering the recurrence of the disease. Therefore, developing a novel system is required for localized drug delivery with a prolonged release in a single dose, enhanced fibre adhesion, retention, and drug penetration to the vaginal mucosa. Nanofiber is the new biomedical application of nanotechnology used as a carrier for effective drug delivery and have a diameter in the order of a few nanometres to over 1 μm (more typically 50~500 nm) and possess unique characteristics, such as: extraordinary high surface area per unit mass, sustained release, enhanced solubility, high drug loading capacity, flexibility, and mechanical properties which make them a better tool to overcome the constraints of vaginal drug delivery carriers in VVC management. In this study, polycaprolactone, gelatine, tea tree oil and luliconazole drug was used for the fabrication of nanofiber. Nanofibers produced and optimized in this research work was characterized by SEM, FTIR, DSC, XRD, swelling study, drug uniformity, entrapment efficiency, contact angle, mucoadhesive test, and mechanical strength. In vitro drug release, drug permeation study, vaginal irritation test and anti-candidal activity were also performed. SEM analysis showed the uniform and less bead-free PCL/gelatine fibres. FTIR proved that there is no interaction between drug and excipients. DSC indicates the absence of characteristic peak of the luliconazole drug in the nanofiber revealed the LCZ was amorphous by the loading of LCZ in the nanofiber. In the swelling study, maximum increment in the swelling was obtained at 4hr. The entrapment efficiency of drug loaded nanofiber was found to be 89.2 ± 0.8 %. The contact angles of blank nanofiber, nanofiber with tea tree oil and LCZ-loaded nanofiber was found to be 46.5, 62.95 and 65.78 respectively. The mucoadhesive force of blank nanofiber, TT oil-loaded nanofiber, and LCZ-loaded nanofiber was obtained as 1000 dynes, 400 dynes, and 300 dynes respectively. The mechanical strength of blank nanofiber, TT oil-loaded fiber, and drug-loaded nanofiber was 0.187 N/mm, 0.148 N/mm, and 0.445 N/m. The release reached 67.7 ± 3.4 % after 48 hours of study which was found more than the release of drug from the suspension and drug release through nanofiber was best addressed by the Korsmeyer-Peppas model. The percentage cumulative drug permeation was found as 54.13 ± 0.32 % within 6 hours for drug with oil loaded nanofiber, 50.43 ± 0.84 % for only drug loaded nanofiber and 31.87 ± 1.13 % for suspension. The zone of inhibition (ZOI) of luliconazole-loaded nanofiber was 12.8 ± 0.53 mm after 48 hours. Thus, the luliconazole loaded nanofiber fabricated for the first time which successfully could work in the anticandidal action for the management of vaginal candidiasis.