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Generation Dependent Safety and Efficacy of Folic Acid Conjugated Dendrimer Based Anticancer Drug Formulations
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Generation Dependent Safety and Efficacy of Folic Acid Conjugated Dendrimer Based Anticancer Drug Formulations
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Journal Article
Generation Dependent Safety and Efficacy of Folic Acid Conjugated Dendrimer Based Anticancer Drug Formulations
2015
Overview
Purpose
Folate conjugated poly(propyleneimine) (PPI) dendrimer (FPPI) mediated anticancer therapy is being extensively discovered throughout the world. The present investigation was aimed at exploring the targeting potential of Melphalan loaded FPPI of different generations (MP-FPPI) for effective management of cancer.
Methods
The MP-FPPI formulations were compared for drug entrapment efficiency,
in vitro
release profile, toxicology, folate receptor blockage assay, cell uptake assay, stability studies, and
in vivo
studies.
Results
Upon increasing the dendrimer generation from fourth to fifth, the drug delivery parameters improved negligibly except the toxicological profile that improved exponentially. MTT assay in case of MCF-7 cells depicted the
IC
50
values of 8 ± 0.15, 0.9 ± 0.02, 0.2 ± 0.01 and 10 ± 0.17 μM, respectively in case of MP-FPPI3, MP-FPPI4, MP-FPPI5, and free Melphalan suggesting folate based targeting to be the efficacious approach to kill cancer cells. The median survival time for tumor bearing mice treated with MP-FPPI3, MP-FPPI4, MP-FPPI5 and free drug was found to be 23, 59, 62 and 26 days, respectively.
Conclusions
The study concludes fourth generation PPI dendrimer to be superior carrier for folate based tumor targeting compared to third and fifth generation based formulations. This work is expected to provide a significant clue in the selection of “dendrimer generation” for folate mediated cancer targeting therapy.
Graphical Abstract
This debut study exploring the effect of generation on the targeting potential of folate-conjugated PPI dendrimer and the outcome is expected to shed valuable information in selection of dendrimer generation.
Publisher
Springer US,Springer Nature B.V
Subject
/ Antineoplastic Agents, Alkylating - administration & dosage
/ Antineoplastic Agents, Alkylating - adverse effects
/ Antineoplastic Agents, Alkylating - pharmacokinetics
/ Antineoplastic Agents, Alkylating - therapeutic use
/ Biomedical and Life Sciences
/ Biomedical Engineering and Bioengineering
/ Cell Survival - drug effects
/ Female
/ Humans
/ Melphalan - administration & dosage
/ Melphalan - pharmacokinetics
/ Pharmacy
/ Toxicity
/ Tumors
