# Pluronic® F127 Polymeric Micelles as Nanocarriers for Pentamidine: Improving Safety and Biological Efficacy Against Leishmania major

## TL;DR

This study explores using Pluronic® F127 micelles to deliver pentamidine for treating leishmaniasis, improving safety and effectiveness.

## Contribution

The novel contribution is the development of PTM-loaded F127 micelles that reduce toxicity while maintaining antiparasitic efficacy.

## Key findings

- PTM-loaded F127 micelles reduced cytotoxicity in macrophages without losing antileishmanial activity.
- Micelles modulated pathways related to oxidative stress and drug resistance in Leishmania major.
- The therapeutic index of PTM was significantly improved in vitro using F127 micelles.

## Abstract

Cutaneous leishmaniasis (CL) is a neglected tropical disease for which current chemotherapeutic options are limited by systemic toxicity (such as hepato-nephrotoxicity, arrhythmia, nausea, vomiting) and difficult administration regimens. Pentamidine (PTM), although effective, exhibits severe dose-limiting adverse effects. Polymeric micelles based on Pluronic® F127 (F127) offer an attractive strategy to improve PTM delivery by enhancing solubility, reducing cytotoxicity, and enabling controlled release. Here, we developed PTM-loaded F127 polymeric micelles and performed a multidisciplinary evaluation combining physicochemical characterization, in vitro biological assays, and gene expression profiling. Dynamic light scattering, UV–visible absorption, fluorescence spectroscopy, and NMR confirmed micelle formation, PTM–polymer interactions, and temperature-dependent assembly. PTM-loaded micelles exhibited biorelevant nanoscale dimensions and preserved stability under physiological conditions. Biological assays demonstrated that F127 micelles markedly reduced PTM cytotoxicity in RAW264.7 macrophages while maintaining potent antileishmanial activity against Leishmania major promastigotes. RT-qPCR analysis revealed modulation of key pathways involved in redox homeostasis, oxidative stress, calcium regulation, apoptosis-like responses, and drug resistance, suggesting that micellar encapsulation influences both PTM bioavailability and parasite stress responses. Overall, PTM-loaded F127 micelles significantly improved the therapeutic index of PTM in vitro. These findings support the potential of F127 polymeric micelles as a promising nanocarrier platform for safer and more effective CL therapy.