Pentamidine-Functionalized Polycaprolactone Nanofibers Produced by Solution Blow Spinning for Controlled Release in Cutaneous Leishmaniasis Treatment

Leishmaniasis, a widespread, neglected infectious disease with limited effective treatments and increasing drug resistance, demands innovative therapeutic approaches. In this study, we report the fabrication of pentamidine (PTM)-loaded polycaprolactone (PCL) nanofibers using solution blow spinning (SBS) as a potential topical delivery system for cutaneous leishmaniasis (CL). Homogeneous PCL fiber mats were produced using a simple SBS set-up with a commercial airbrush after optimizing several working parameters. Drug release studies demonstrated sustained PTM release profile over time, which was mechanistically modeled by utilizing the complete nanofiber diameter distribution, obtained from SEM analysis of the blow-spun material. FTIR and XRD analyses were performed to investigate the drug-polymer interactions, revealing molecularly dispersed PTM at low-proportion drug/polymers and partial crystallinity at high loadings. The released PTM exhibited significant leishmanicidal activity against <i>Leishmania major</i> promastigotes. Biological investigations showed that SBS-formulated PTM treatment was consistent with the downregulation of parasite genes involved in cell division and DNA replication (<i>cycA</i>, <i>cyc6</i>, <i>pcna</i>, <i>top2</i>, <i>mcm4</i>) and upregulation of the drug response gene (<i>prp1</i>). The controlled delivery of PTM within SBS-fabricated PCL nanofibers provides an effective therapeutic approach to tackle CL and, through the incorporation of additional drugs, could be extended to address a broader range of cutaneous infections.