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.
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Authors | N Sanoj Rejinold, Thejus Baby, K P Chennazhi, R Jayakumar |
Journal | Journal of biomedical nanotechnology
(J Biomed Nanotechnol)
Vol. 11
Issue 3
Pg. 392-402
(Mar 2015)
ISSN: 1550-7033 [Print] United States |
PMID | 26307823
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Delayed-Action Preparations
- Hydrogels
- Nanocapsules
- Polymers
- Receptors, Vitronectin
- integrin alphavbeta1
- poly-N-vinylcaprolactam
- Caprolactam
- Fibrinogen
- Megestrol Acetate
- Fluorouracil
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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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