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Poly(ethylene glycol)-Modified PAMAM-Fe3O4-Doxorubicin Triads with the Potential for Improved Therapeutic Efficacy: Generation-Dependent Increased Drug Loading and Retention at Neutral pH and Increased Release at Acidic pH

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Title Poly(ethylene glycol)-Modified PAMAM-Fe3O4-Doxorubicin Triads with the Potential for Improved Therapeutic Efficacy: Generation-Dependent Increased Drug Loading and Retention at Neutral pH and Increased Release at Acidic pH
 
Creator NIGAM, S
CHANDRA, S
NEWGREEN, DF
BAHADUR, D
CHEN, QZ
 
Subject POLY(AMIDOAMINE) DENDRIMERS
PAMAM DENDRIMERS
SPECTROSCOPY
STABILITY
LIPOSOMES
DELIVERY
NANOPARTICLES
DERIVATIVES
HYDROGEL
BINDING
 
Description Polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles are a promising drug-delivery system that can enhance the therapeutic effects of chemotherapy drugs, such as doxorubicin (DOX), with minimized side effects. This work explores the optimization of the potential therapeutic efficiency of PAMAM-Fe3O4-DOX triads. Different generations (G(3), G(5), and G(6)) of PAMAMs were synthesized and modified with poly(ethylene glycol) (PEG) and then used to encapsulate glutamic acid-modified Fe3O4 nanoparticles. The Fe3O4-dendrimer carriers (Fe3O4-DG(x) where x = the generation 3, 5, or 6 of dendrimers) were electrostatically conjugated with drug DOX. The loading and releasing efficiencies of DOX increased with the PAMAM generation from 3 to 6. The loading efficiencies of DOX molecules were 87, 93, and 96% for generations 3, 5, and 6, respectively. At pH 5, the DOX release efficiencies within 24 h were approximately 60, 68, and 80% for generations 3, 5, and 6, respectively. At pH 7.4, the DOX releasing efficiency was as low as similar to 15%. Compared to the negative control, the PAMAM-Fe3O4-DOX triads showed only mild toxicity against human cervical adenocarcinoma cell line He La at pH 7.4, which indicated that DOX can be fairly benignly carried and sparingly released until PAMAM-Fe3O4-DOX is taken up into the cell.
 
Publisher AMER CHEMICAL SOC
 
Date 2014-12-29T05:55:08Z
2014-12-29T05:55:08Z
2014
 
Type Article
 
Identifier LANGMUIR, 30(4)1004-1011
0743-7463
http://dx.doi.org/10.1021/la404246h
http://dspace.library.iitb.ac.in/jspui/handle/100/17246
 
Language English