Toxicological investigation of surface engineered fifth generation poly (propyleneimine) dendrimers in vivo

Dutta, Tathagata, Garg, Minakshi, Dubey, Vaibhav, Mishra, Dinesh, Singh, Kanhaiya, Pandita, Deepti, Singh, Ajeet K., Ravi, Alok K., Velpandian, Thirumurthy and Jain, Narendra K. (2008) Toxicological investigation of surface engineered fifth generation poly (propyleneimine) dendrimers in vivo. Nanotoxicology, 2 2: 62-70. doi:10.1080/17435390802105167


Author Dutta, Tathagata
Garg, Minakshi
Dubey, Vaibhav
Mishra, Dinesh
Singh, Kanhaiya
Pandita, Deepti
Singh, Ajeet K.
Ravi, Alok K.
Velpandian, Thirumurthy
Jain, Narendra K.
Title Toxicological investigation of surface engineered fifth generation poly (propyleneimine) dendrimers in vivo
Formatted title
Toxicological investigation of surface engineered fifth generation poly (propyleneimine) dendrimers in vivo
Journal name Nanotoxicology   Check publisher's open access policy
ISSN 1743-5390
Publication date 2008-01-01
Sub-type Article (original research)
DOI 10.1080/17435390802105167
Open Access Status Not yet assessed
Volume 2
Issue 2
Start page 62
End page 70
Total pages 9
Editor V. Stone
Place of publication United Kingdom
Publisher Informa Healthcae
Language eng
Subject C1
860899 Human Pharmaceutical Products not elsewhere classified
111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract Dendrimers are three dimensional polymers, nanoscopic in size, most widely explored in the field of drug delivery in recent times. In order to establish these polymers as controlled and targeted drug delivery systems, they should be non-toxic, biocompatible and biodegradable. The purpose of the present study is to investigate the toxicological profile of fifth generation poly (propyleneimine) dendrimers (PPI) and some of its surface engineered derivatives. Functionalized PPI dendrimers (TPPI, MPPI and TuPPI) were synthesized to mask the primary amino groups responsible for the positive charge and associated toxicity. Each polymer is administered in three different doses: 2.5 mg/kg, 25 mg/kg and 250 mg/kg (i.e., low, intermediate and high dose) to Wister rats, and blood as well as tissue samples were collected after 24 h and 15 days. Decrease in RBC count and hemoglobin content after 24 h, in case of animals administered with PPI suggests hemolytic activity of PPI. Significant increase in SGOT, SGPT and LDH indicates that PPI causes severe damage to the membranes of the various tissues of the body, especially that of the liver leading to the leakage of these marker enzymes in blood. Sections of liver of animals administered with PPI showed signs of tissue degeneration after 24 h. No signs of toxicity were observed in case of animals administered with functionalized PPI. Neither PPI nor its surface engineered derivatives showed any signs of immunogenicity. It can be concluded that functionalization of dendrimers leads to drastic reduction of toxicity and increases biocompatibility.
Keyword Biocompatibility
In vivo toxicity
Poly (propyleneimine) dendrimers
Surface functionalization of dendrimers
Toxicity of dendrimers
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Pharmacy Publications
 
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Created: Wed, 08 Apr 2009, 20:15:07 EST by Elizabeth Pyke on behalf of School of Pharmacy