Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 135, Issue -, Pages 175-182Publisher
ELSEVIER
DOI: 10.1016/j.colsurfb.2015.07.070
Keywords
PEG; Dendrimer; Drug delivery; Encapsulation; Spectroscopy; TEM; Modeling
Funding
- Natural Sciences and Engineering Research Council of Canada (NSERC)
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Synthetic polymers poly(ethylene glycol) (PEG), methoxypoly (ethylene glycol) polyamidoamine (mPEG-PAMAM-G3) and polyamidoamine (PAMAM-G4) dendrimers were used for encapsulation of antibiotic drug doxorubicin (Dox) and its analogue N-(trifluoroacetyl)doxorubicin (FDox) in aqueous solution at pH 7.4. Multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling were used to characterize the drug binding process to synthetic polymers. Structural analysis showed that drug-polymer binding occurs via both H-bonding and hydrophobic contacts. The order of binding is PAMAM-G4 > mPEG-PAMAM-G3 > PEG-6000 with Dox forming more stable conjugate than FDox. Transmission electron microscopy showed significant changes in carrier morphology with major changes in the shape of the polymer aggregate as drug encapsulation occurred. Modeling also showed that drug is located in the surface and in the internal cavities of PAMAM with the free binding energy of -4.14 kcal/mol for Dox and -3.93 kcal/mol for FDox, indicating of spontaneous drug polymer-interaction at room temperature. (C) 2015 Elsevier B.V. All rights reserved.
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