Multi Drug Loaded Thermo-Responsive Fibrinogen-graft-Poly(N-vinyl Caprolactam) Nanogels for Breast Cancer Drug Delivery

• Published in: Journal of biomedical nanotechnology Vol. 11; no. 3; p. 392
• Main Authors: Rejinold, N Sanoj, Baby, Thejus, Chennazhi, K P, Jayakumar, R
• Format: Journal Article
• Language: English
• Published: United States 01-03-2015
• Subjects: Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - chemistry; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Caprolactam - analogs & derivatives; Caprolactam - chemistry; Cell Line, Tumor; Cell Survival - drug effects; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemical synthesis; Diffusion; Fibrinogen - chemistry; Fibrinogen - pharmacokinetics; Fluorouracil - administration & dosage; Fluorouracil - chemistry; Humans; Hydrogels - chemical synthesis; Megestrol Acetate - administration & dosage; Megestrol Acetate - chemistry; Nanocapsules - administration & dosage; Nanocapsules - chemistry; Nanocapsules - ultrastructure; Particle Size; Polymers - chemistry; Receptors, Vitronectin - metabolism; Temperature
• ISSN: 1550-7033
• DOI: 10.1166/jbn.2015.1911

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 α5β1-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 100-120 nm sized nanogels of fib-graft-PNVCL (LCST = 35 ?1 'C) was prepared using CaCl2 cross-linker. The 5-FU/Meg-fib-graft-PNVCL NGs showed a particle size of 150-170 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.