title: Generation dependent safety and efficacy of folic acid conjugated dendrimer based anticancer drug formulations.
abstract: OBJECTIVE
  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.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, 470003, MP, India, prashant_pharmacy04@rediffmail.com.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kesharwani
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Tekade
authors.forename: Narendra K
authors.initials: NK
authors.lastname: Jain
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004355:Drug Stability; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D011126:Polypropylenes / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018906:Antineoplastic Agents, Alkylating; D050091:Dendrimers; D004337:Drug Carriers; D011126:Polypropylenes; C443641:poly(propyleneimine); D005492:Folic Acid; D008558:Melphalan