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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.
AuthorsN Sanoj Rejinold, Thejus Baby, K P Chennazhi, R Jayakumar
JournalJournal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 11 Issue 3 Pg. 392-402 (Mar 2015) ISSN: 1550-7033 [Print] United States
PMID26307823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Delayed-Action Preparations
  • Hydrogels
  • Nanocapsules
  • Polymers
  • Receptors, Vitronectin
  • integrin alphavbeta1
  • poly-N-vinylcaprolactam
  • Caprolactam
  • Fibrinogen
  • Megestrol Acetate
  • Fluorouracil
Topics
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, chemistry)
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Caprolactam (analogs & derivatives, chemistry)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Delayed-Action Preparations (administration & dosage, chemical synthesis)
  • Diffusion
  • Fibrinogen (chemistry, pharmacokinetics)
  • Fluorouracil (administration & dosage, chemistry)
  • Humans
  • Hydrogels (chemical synthesis)
  • Megestrol Acetate (administration & dosage, chemistry)
  • Nanocapsules (administration & dosage, chemistry, ultrastructure)
  • Particle Size
  • Polymers (chemistry)
  • Receptors, Vitronectin (metabolism)
  • Temperature

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