Amphotericin B PLGA nanoparticles loaded dissolving microneedle patches in treating cutaneous fungal infections

Abstract

Cutaneous fungal infections pose a significant health challenge, particularly in deeper skin layers where topical treatments are ineffective. Amphotericin B (AmB) is the gold standard for treating fungal infections, but its poor solubility limits its transdermal delivery. In this work, AmB was loaded into polylactic-co-glycolic acid nanoparticles (PLGA NP) via the solvent deposition method. The resulting NP had an average size of 311.54 ± 2.08 nm and a polydispersity index (PDI) of 0.22 ± 0.12. After reconstitution, the particle size decreased to 209.89 ± 1.10 nm, with a PDI of 0.10. The encapsulation efficiency was 98.59 ± 0.10%. These AmB-loaded PLGA NP were then incorporated into dissolving microneedles (MNs) using a sequential loading method. The MNs demonstrated adequate mechanical strength to deliver the NP into the deep dermal layers, with an insertion depth of 363.5 μm and a height reduction of only 3.56 ± 2.10% under compression. In vitro release studies revealed an initial burst release of 60% within 1 h, followed by a slower release over four days. Ex vivo skin deposition and permeation studies demonstrated remarkable deposition of the drug into the dermis skin layers. This delivery system offers significant potential for treating cutaneous fungal infections, combining the benefits of sustained drug release and targeted delivery to deep skin layers.