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Antitumor efficacy of doxorubicin encapsulated within PEGylated poly(amidoamine) dendrimers
Author(s) -
Liao Huihui,
Liu Hui,
Li Yulin,
Zhang Mengen,
Tomás Helena,
Shen Mingwu,
Shi Xiangyang
Publication year - 2014
Publication title -
journal of applied polymer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.575
H-Index - 166
eISSN - 1097-4628
pISSN - 0021-8995
DOI - 10.1002/app.40358
Subject(s) - dendrimer , pegylation , poly(amidoamine) , amidoamine , polyethylene glycol , peg ratio , chemistry , doxorubicin , drug delivery , combinatorial chemistry , polymer chemistry , biophysics , organic chemistry , medicine , surgery , finance , chemotherapy , economics , biology
We report here a general approach to using poly(amidoamine) (PAMAM) dendrimers modified with polyethylene glycol (PEG) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for in vitro cancer therapy applications. In this approach, PEGylated PAMAM dendrimers were synthesized by conjugating monomethoxypolyethylene glycol with carboxylic acid end group ( m PEG‐COOH) onto the surface of generation 5 amine‐terminated PAMAM dendrimer (G5.NH 2 ), followed by acetylation of the remaining dendrimer terminal amines. By varying the molar ratios of m PEG‐COOH/G5.NH 2 , G5.NHAc‐ m PEG n ( n = 5, 10, 20, and 40, respectively) with different PEGylation degrees were obtained. We show that the PEGylated dendrimers are able to encapsulate DOX with approximately similar loading capacity regardless of the PEGylation degree. The formed dendrimer/DOX complexes are water soluble and stable. In vitro release studies show that DOX complexed with the PEGylated dendrimers can be released in a sustained manner. Further cell viability assay in conjunction with cell morphology observation demonstrates that the G5.NHAc‐ m PEG n /DOX complexes display effective antitumor activity, and the DOX molecules encapsulated within complexes can be internalized into the cell nucleus, similar to the free DOX drug. Findings from this study suggest that PEGylated dendrimers may be used as a general drug carrier to encapsulate various hydrophobic drugs for different therapeutic applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 40358.