Development, Optimisation, and Evaluation of a Ciclopirox Olamine-Loaded Spanlastic Nanogel with Microneedle Pen Pre-Treatment for Enhanced Transungual Drug Delivery
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Abstract
Background: Onychomycosis is a chronic fungal infection of the nails that is difficult to treat in which the dense keratinised nail plate restricts drug permeation.
Objective: To develop, optimise ciclopirox olamine (CPO) loaded spanlastic (SP) nanogel formulations and investigate the potential of microneedle (MN) pre-treatment to enhance CPO permeation into the nail as a topical approach for the treatment of onychomycosis.
Methods: The formulations were designed and optimised using a Box–Behnken experimental design. SPs were prepared using different concentrations of Span 60 and Tween 80. The optimised SP formulation was characterised and subsequently incorporated into Carbopol 934P gel bases to prepare SP nanogels, which were evaluated to select the optimum formulation. Ex vivo permeation studies using sheep hooves and human fingernails were conducted to determine the amounts of CPO permeated through and deposited within the nail from the optimum SP nanogel, with and without MN pre-treatment.
Results: The optimised SP formulation exhibited an appropriate vesicle size, PDI, and entrapment efficiency, with enhanced antifungal activity. The optimum SP nanogel showed suitable vesicle size, PDI, viscosity, drug content, and drug release characteristics. The ex vivo permeation study demonstrated greater CPO deposition from the SP nanogel than from the plain gel, with 1.54-fold and 1.73-fold increases in deposition in sheep hooves and human fingernails, respectively. Furthermore, MN pen pre-treatment markedly enhanced CPO deposition, resulting in 76% and 55% increases in sheep hooves and human fingernails, respectively, compared with the corresponding formulations without MN pre-treatment.
Conclusion: The combination of SP nanogel formulation with MNs represents a promising strategy for enhancing transungual drug delivery for the topical treatment of onychomycosis.