D-082 | Concomitant Treatment with Microfluidic-Assisted Tadalafil- and Paclitaxel-Loaded Polymeric Micelles Enables Dose Reduction and Enhances Cytotoxicity Against Glioblastoma Multiforme

Disorders of the Nervous System
Author: Luciano Fiore | Email: lfiore@fmed.uba.ar

Luciano Fiore^1°2°, Noelia Anahi Soria^1°2°, Greta Bolzi^1°2°,  Julia Gallino^1°2°, Irina Muntaabski^1°2°, Rodrigo Lloyd^1°2°, Paola Rojas^3°,  Diego Chiappetta^4°, Marcela Moretton^4°, Patricia Gargallo^5°, Biscochea D^5°, Guevara M^5°, Bastianello M^5° and Policastro L^1°2°

^1° Laboratory of Nanomedicine, Comisión Nacional de Energía atómica (CNEA), Av. General Paz 1499, B1650KNA, San Martín, Buenos Aires, Argentina.
^2° Instituto Nanociencias y Nanotecnología, Comisión Nacional de Energía atómica (CNEA), Av. General Paz 1499, B1650KNA, San Martín, Buenos Aires, Argentina
^3° Laboratory of Hormonal Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME CONICET), Buenos Aires, Argentina.
^4° Instituto de Tecnología Farmacéutica y Biofarmacia (InTecFyB), Universidad de Buenos Aires, Buenos Aires 1113, Argentina.
^5° Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC). Argentina.

Polymeric micelles (PMs) are nanosized carriers for delivering hydrophobic drugs, like paclitaxel (PX). Multi-drug combinations have gained traction to enhance PX therapeutic efficacy. Tadalafil (TD), have demonstrated immunomodulatory activity in combination with checkpoint inhibitors. Thus, combining TD with PX may reduce the chemotherapy dose needed to achieve a therapeutic response. This study aimed to evaluate the in vitro performance of PX-loaded and TD-loaded PM based on co-polymer of mPEG-PCL and produced by microfluidic (MF). These PMs were characterized in size, polydispersity index (PDI), stability, drug concentration and release. Furthermore, PMs performed by MF were compared to the commercially available formulation Abraxane®, as well as with PMs prepared using conventional methods (CM). Globally MF PMs exhibited an average size of 92,855 ± 1,330 and a narrow PDI. In vitro assays revealed that PX-loaded PMs produced by MF exhibited higher antitumor activity compared to PX-loaded PM performed by CM in the glioblastoma multiforme (GM) cell line U251 and a primary culture of GM. Moreover, the concomitant treatment with MF-based PX and TD PMs resulted in a significant increase in cytotoxicity at lower doses for both cell lines. Overall, these findings confirmed that PMs produced through MF exhibit superior performance compared to CM PX-loaded PMs, presenting an attractive alternative for the development of novel nanosized carriers for anticancer therapy.