# Tetronic® 1307-Based Polymeric Micelles and Thermoresponsive Gels for the Co-Delivery of Pentamidine and Miltefosine

## TL;DR

This study explores using a special polymer to deliver two antiparasitic drugs together in a way that could improve treatment and reduce side effects.

## Contribution

A novel co-delivery system using Tetronic® 1307 enables synergistic antiparasitic therapy with thermoresponsive gel formation.

## Key findings

- MF and PTM were successfully co-delivered using T1307-based micelles and gels.
- The drug combination showed synergistic effects against Leishmania major.
- Thermoresponsive gels formed at physiological temperatures, suitable for topical use.

## Abstract

Background: Pentamidine isethionate (PTM) and miltefosine (MF) are clinically relevant antiparasitic agents whose use is limited by toxicity, emerging resistance, and the lack of effective co-delivery strategies. Tetronic® 1307 (T1307), an amphiphilic and thermoresponsive block copolymer, was investigated as a carrier to enable their combination therapy. Methods: PTM and MF were formulated in T1307-based micelles and thermoresponsive gels. The systems were characterized by small-angle neutron scattering (SANS), dynamic light scattering (DLS), and nuclear magnetic resonance spectroscopy (NMR). Antiparasitic activity was evaluated against Leishmania major promastigotes. Results: MF formed stable micelles that efficiently incorporated PTM, generating a “drug-in-drug” architecture. While T1307 alone showed limited PTM loading, MF promoted mixed micelle formation and enhanced PTM incorporation. At physiological temperature and adequate copolymer concentrations, drug-loaded micelles formed thermoreversible gels suitable for topical application. The combined formulations preserved drug activity and exhibited synergistic effects against L. major. Conclusions: T1307 is a promising platform for the co-delivery of PTM and MF, enabling synergistic combination therapy and thermoresponsive gel formation with potential to reduce systemic toxicity and improve treatment administration.