Background: Methotrexate (MTX) is a water-insoluble, anti-tumor agent, 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 was aimed for successfully incorporating of MTX into novel-targeted Pluronic (PEO-PPOPEO 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.
Method: 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 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 69%, 69.5% and 66% at 12 h whereas 80.89%, 77.67% and
78.54% after 24 h respectively and reveals sustained release. MTX loaded PF127/SDS micelles showed high Partition coefficient and negative free energy of solubilization compared to PF127 and PF127/PC which signifies self-assembly behavior
and thermodynamic stability towards dissociation to be higher.
Conclusion: Finally concluded that MTX loaded PF127/SDS micelles act as a potential anticancer delivery system in comparison to PF127/PC and PF127 to combat against tumor cells by enhancing its 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 of MTX.