Thermosensitive Poloxamer Liposomal Gel for Sustained FTA Delivery Enhances Anti-Breast Cancer Efficacy and Biosafety.

INTRODUCTION

FTA is a new FT derivative developed by our team by modifying FT with aspirin, and it has been shown to boost anti-breast cancer activity.

METHODS

To significantly enhance the anti-breast cancer efficacy and biosafety of FTA, this study employed Poloxamer F127 and Poloxamer F68 to construct a composite carrier system, successfully prepared FTA-loaded liposomes (FTA-LN) and their thermosensitive gel formulation (FTA-LN-TSG), with systematic in vitro and in vivo assessments performed.

RESULTS

Simultaneously, FTA-LN exhibited an average particle size of 131.03 ± 4.35 nm, polydispersity index (PDI) of 0.265 ± 0.003, zeta potential of -21.46 ± 2.49 mV, and encapsulation efficiency of 94.55 ± 1.10%. FTA-LN followed first-order kinetics, with a cumulative release rate of 68.48% within 4 hours. Conversely, FTA-LN-TSG displayed sustained release characteristics consistent with Higuchi kinetics, reaching a cumulative release of 52.56% at 8 hour. In vitro efficacy evaluation revealed that FTA-LN-TSG exhibited significantly superior inhibitory effects against breast cancer cells compared to FTA (24 h and 48 h inhibition rates: 2.72- and 5.02-fold of FTA; cell migration rate: 37% of FTA). Furthermore, FTA-LN-TSG demonstrated significant differences in inducing apoptosis and cell cycle arrest (Total apoptosis rate of FTA: 25.74, total apoptosis rate of FTA-LN-TSG: 48.84%). Pharmacokinetic results indicated that FTA-LN-TSG exhibited a 3.5-fold prolongation in half-life (t1/2), and a 6-fold extension in time to peak concentration (Tmax) compared with FTA group. In tumor model mice, The FTA-LN-TSG injected beside the tumor was achieved a tumor inhibition rate of 64.42 ± 5.60% (1.82-fold of the FTA group, 1.45-fold of the S-1 group) with favorable biosafety.

CONCLUSION

In summary, as a novel drug delivery system, FTA-LN-TSG may represent a promising option for breast cancer therapy.