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Generation dependent cancer targeting potential of poly(propyleneimine) dendrimer.

Abstract
Dendrimer-mediated delivery of bioactive is a successful and widely explored concept. This paper desribes comparative data pertaining to generation dependent cancer targeting propensity of Poly(propyleneimine) (PPI) dendrimers. This debut report reportsthe drug targeting and antciancer potential of different dendrimer generations. PPI dendrimers of different generations (3.0G, 4.0G and 5.0G) were synthesized and loaded with Melphalan. Results from loading, hemolysis, hematologic, cytotoxicty and flow cytometry assay depicted that as the generation of dendrimer increased from fourth to fifth, the only parameter i.e. toxicty is increased exponentionally. However, others parameters, i.e. loading, sustained release behavior, and targeting efficacy increased negligibly. Kaplan-Meier survival curves clearly depicted comparable therapeutic potential of PPI4M with PPI5M. In vivo investigations in Balb/c mice again favored 4.0G PPI dendrimer to be preferable nanocarrier for anticancer drug delivery owing to analogous anticancer potential. The outcomes of the investigation evidently projects 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer in respect of its drug delivery benefit as well as superior biocompatibility. Thus, much against the common belief, 4.0G PPI dendrimers may be considered to be optimum in respect of drug delivery precluding the use of much more toxic 5.0G PPI dendrimer, which offers no benefit over 4.0G.
AuthorsPrashant Kesharwani, Rakesh K Tekade, Narendra K Jain
JournalBiomaterials (Biomaterials) Vol. 35 Issue 21 Pg. 5539-48 (Jul 2014) ISSN: 1878-5905 [Electronic] Netherlands
PMID24731713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Dendrimers
  • Drug Carriers
  • Polypropylenes
  • poly(propyleneimine)
Topics
  • Animals
  • Cell Line, Tumor
  • Dendrimers (chemistry, pharmacology)
  • Drug Carriers
  • Drug Delivery Systems (methods)
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms (drug therapy)
  • Polypropylenes (chemistry, pharmacology)

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