Liposomal glytrexate formulation: improving antitumour efficacy and minimizing toxicity in breast cancer therapy

Abstract

Cancer remains a critical global health challenge with increasing incidence rates. This study reports the first successful encapsulation of glytrexate (GTX), a novel 6-substituted-pyrrolo [2,3-d] pyrimidine compound, into liposomes. This innovative formulation increases the stability, half-life, and bioavailability of GTX while significantly reducing toxicity. GTX liposomes, with a uniform spherical shape and an average particle size of 121.7 ± 2.9 nm, demonstrated a satisfactory encapsulation efficiency (24.2 ± 0.99 %). Compared to the free drug, GTX liposomes exhibited significantly enhanced inhibitory effects on 4 T1, A549, and MCF-7 cells in vitro. The pharmacokinetic analysis showed prolonged circulation (T_1/2: 3.82 h vs. 1.86 h) and increased systemic exposure (AUC_0–∞: 31975.79 vs. 11,545.86 μg·h/L). In vivo studies further confirmed their efficacy, as they substantially reduced tumour growth by 50 %, decreasing lung metastasis in 4 T1 cell models, and minimizing GTX-related side effects. These findings highlight the potential of liposomal GTX formulations to improve breast cancer treatment outcomes.