title: Multi Drug Loaded Thermo-Responsive Fibrinogen-graft-Poly(N-vinyl Caprolactam) Nanogels for Breast Cancer Drug Delivery.
abstract: 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.
authors: N Sanoj
authors: NS
authors: Rejinold
authors: Thejus
authors: T
authors: Baby
authors: K P
authors: KP
authors: Chennazhi
authors: R
authors: R
authors: Jayakumar
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002209:Caprolactam / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis; D004058:Diffusion; D005340:Fibrinogen / Q000737:chemistry / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis; D019290:Megestrol Acetate / Q000008:administration & dosage / Q000737:chemistry; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D019030:Receptors, Vitronectin / Q000378:metabolism; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D053769:Nanocapsules; D011108:Polymers; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1; C086861:poly-N-vinylcaprolactam; D002209:Caprolactam; D005340:Fibrinogen; D019290:Megestrol Acetate; D005472:Fluorouracil