Background: Methotrexate (MTX) is a water-insoluble, anti-tumor agent that causes adverse
effects like bone marrow suppression, chronic interstitial obstructive pulmonary disease, hepatotoxicity,
leukopenia, interstitial pneumonitis and nephrotoxicity with slow drug release rate.
Objective: The present study aimed to successfully incorporate MTX into novel-targeted Pluronic (PEOPPO-
PEO tri-block co-polymer) F127 polymeric micelles intended for intravenous administration with
improved drug loading and sustained release behavior necessary to achieve better efficacy of MTX.
Methods: MTX-loaded Pluronic F127 micelles were characterized for critical micelle concentration,
particle size and zeta potential, 1H NMR, drug loading, encapsulation efficiency characterization, cell
uptake, in vitro release study along with partition coefficient and solubilization thermodynamics.
Results: The micellar formulation resulted in nano size 27.32±1.43nm of PF127/SDS, as compared to
Pluronic F127 micelles or PF127/Phosphatidyl choline which were 30.52±1.18nm and 154.35±5.5nm in
size, respectively. The uptake of PF127/SDS micellar formulation incorporating Rhodamine 123 in
MCF7 cancer cells was found to be higher (84.25%) than PF127/PC, PF127 and MTX i.e. 66.26%,
73.59% and 53% respectively. The in vitro MTX release from PF127, PF127/SDS and PF127/PC polymeric
micelles formulations was observed to be 69%, 69.5% and 66% at 12 h whereas 80.89%,
77.67% and 78.54% after 24 h, respectively and revealed a sustained release. MTX-loaded PF127/SDS
micelles showed high partition coefficient and negative free energy of solubilization compared to PF127
and PF127/PC which signify self-assembly behavior and thermodynamic stability towards higher dissociation.
Conclusion: It was finally concluded that MTX-loaded PF127/SDS micelles act as a potential anticancer
delivery system in comparison to PF127/PC and PF127 to combat tumor cells by enhancing their cellular
uptake targeting with sustained release pattern and reducing the thermodynamic instability. Thus,
PF127/SDS micellar formulation can provide a useful alternative dosage form for intravenous administration