NDLI: Zwitterionic Chitosan-Polyamidoamine Dendrimer Complex Nanoparticles as a pH-Sensitive Drug Carrier

Content Provider	PubMed Central
Author	Liu, Karen C. Yeo, Yoon
Abstract	Polyamidoamine (PAMAM) dendrimers have been widely explored as carriers of therapeutics and imaging agents. However, amine-terminated PAMAM dendrimers is rarely utilized in systemic applications due to its cytotoxicity and risk of opsonization, caused by its cationic charges. Such undesirable effects may be mitigated by shielding the PAMAM dendrimer surface with polymers that reduce the charges. However, this shielding may also interfere with PAMAM dendrimers’ ability to interact with target cells, thus reducing cellular uptake and overall efficacy of the delivery system. Therefore, we propose to use zwitterionic chitosan (ZWC), a new chitosan derivative, which has a unique pH-sensitive charge profile, as an alternative biomaterial to modify the cationic surface of PAMAM dendrimers. Stable electrostatic complex of ZWC and PAMAM dendrimers was formed at pH 7.4, where the PAMAM dendrimer surface was covered with ZWC, as demonstrated by fluorescence spectroscopy and transmission electron microscopy. The presence of ZWC coating protected red blood cells and fibroblast cells from hemolytic and cytotoxic activities of PAMAM dendrimers, respectively. Confocal microscopy showed that the protective effect of ZWC disappeared at low pH as the complex dissociated due to the charge conversion of ZWC, allowing PAMAM dendrimers to enter cells. These results demonstrate that ZWC is able to provide a surface coverage of PAMAM dendrimers in a pH-dependent manner and, thus, enhance the utility of PAMAM dendrimers as a drug carrier to solid tumors with acidifying microenvironment.
Related Links	http://dx.doi.org/10.1021/mp300522p
Ending Page	1704
Page Count	10
Starting Page	1695
File Format	PDF
ISSN	15438384
e-ISSN	15438392
Journal	Molecular pharmaceutics
Issue Number	5
Volume Number	10
Language	English
Publisher Date	2013-05-06
Access Restriction	Open
Subject Keyword	Molecular Medicine Drug Discovery Pharmaceutical Science Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Molecular Medicine Pharmaceutical Science

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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