This study aims at the targeted delivery of 5-fluorouracil (5-FU) and Megestrol acetate (Meg) loaded fibrinogen-graft-poly(N-Vinyl caprolactam) nanogels (5-FU/Meg-fib-graft-PNVCL NGs) toward 5 1-integrins receptors expressed on breast cancer cells to have enhanced anti-cancer effect in vitro. To achieve this aim, we developed biocompatible thermoresponsive fib-graft-PNVCL NGs using fibrinogen and carboxyl terminated PNVCL via EDC/NHS amidation reaction. The Lower Critical Solution Temperature (LCST) of fib-graft-PNVCL could be tuned according to PNVCL/fibrinogen compositions. The 100120 nm sized nanogels of fib-graft-PNVCL (LCST = 35 \textpm 1 \textdegreeC) was prepared using CaCl2 cross-linker. The 5-FU/Meg-fib-graft-PNVCL NGs showed a particle size of 150170 nm size. The drug loading efficiency with 5-FU was 62% while Meg showed 74%. The 5-FU and Meg release was prominent above LCST than below LCST. The multi drug loaded fib-graft-PNVCL NGs showed enhanced toxicity, apoptosis and uptake by breast cancer (MCF-7) cells compared to their individual doses above their LCST. The in vivo assessment in Swiss albino mice showed sustained release of Meg and 5-FU as early as 3 days, confirming the therapeutic efficiency of the formulation. These results demonstrate an enhanced platform for the future animal studies on breast tumor xenograft model.
S. N. Rejinold, Baby, T., Chennazhi, K. P., and Dr. Jayakumar Rangasamy, “Multi Drug Loaded Thermo-Responsive Fibrinogen-graft-Poly(N-vinyl Caprolactam) Nanogels for Breast Cancer Drug Delivery”, Journal of Biomedical Nanotechnology, vol. 11, pp. 392-402, 2015.