Fabrication of miconazole nitrate solid lipid nanoparticle loaded microneedle patches for the treatment of Candida albicans biofilms

Abstract

The present study aimed to develop miconazole nitrate solid lipid nanoparticle (SLN) loaded polymeric microneedle (MN) patches (SPs) via the vacuum micromolding approach. The SLNs were fabricated through melt emulsification of stearic acid using Tween 80. SPs were prepared using chitosan, gelatin (as base materials) and polyethylene glycol 400 (as a plasticizer). The prepared formulations were evaluated for various physicochemical parameters, including particle size, polydispersity index, encapsulation efficiency, loading capacity (in the case of SLNs), folding endurance, % swelling and insertion ability (in the case of SPs). Scanning electron microscopy and differential scanning calorimetry (DSC) studies were carried out for morphological and thermal analysis, respectively. Phase analysis was carried out via X-ray diffraction (XRD). In vitro tensile strength, drug release, anti-biofilm activity and in vivo anti-biofilm activity were studied to assess the efficiency of the SLN loaded polymeric formulation. Miconazole nitrate containing SLNs appeared as smooth-surfaced aggregates and displayed a particle diameter of ∼224 nm, polydispersity index of ∼0.32, encapsulation efficiency of ∼88.88% and loading capacity of ∼8.88%. SPs exhibited evenly aligned, uniform-surfaced, sharp-tipped projections, with an acceptable folding endurance of ∼300 and % swelling of ∼359%. DSC and XRD results confirmed the incorporation of the drug within the solidified lipid matrix as an amorphous solid. The miconazole nitrate lipidic nanoparticle containing polymeric formulation exhibited a tensile strength ∼1.35 times lower than the pure drug loaded counterpart. During in vitro studies, SPs released ∼94% miconazole nitrate within 150 minutes and reduced the mass of the Candida albicans (C. albicans) biofilm by ∼79%. After 10 days of treatment with SPs, C. albicans infected wounds were healed, confirming that the prepared formulations can be used for the management of fungal biofilms.