Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload

Parag Kolhe, Jayant Khandare, Omathanu Pillai, Sujatha Kannan, Mary Lieh-Lai, Rangaramanujam M. Kannan

Research output: Contribution to journalArticlepeer-review

Abstract

Dendrimers are emerging as a relatively new class of polymeric biomaterials with applications in drug delivery, and imaging. Achieving a high drug payload in dendrimers, and understanding the therapeutic effect of the dendrimer-drug conjugates are receiving increasing attention. A high drug payload nanodevice was obtained by covalent conjugation of ibuprofen to a polyamidoamine (PAMAM-G4-OH) dendrimer. Using DCC as a coupling agent, 58 molecules of ibuprofen were covalently conjugated to one molecule of generation 4 PAMAM-OH dendrimer. Cellular entry of the fluoroisothiocynate (FITC)-labeled dendrimer-drug conjugate was evaluated in vitro by using human lung epithelial carcinoma A549 cells by flow cytometry, confocal microscopy and UV/Visible spectroscopy. The pharmacological activity of the dendrimer-ibuprofen conjugate was compared to pure ibuprofen at various time points by measuring the suppression of prostaglandin E2. Significant amounts of the conjugate entered the cells rapidly within 15 min. Suppression of prostaglandin was noted within 30 min for the dendrimer-drug conjugates versus 1 h for the free ibuprofen. The results suggest that dendrimers with high drug payload improve the drug's efficacy by enhanced cellular delivery, and may produce a rapid pharmacological response. These dendrimer-drug conjugates can potentially be further modified by attaching antibodies and ligands for targeted drug delivery.

Original languageEnglish (US)
Pages (from-to)660-669
Number of pages10
JournalBiomaterials
Volume27
Issue number4
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

Keywords

  • Cellular transport
  • Dendrimer-drug conjugates
  • Drug delivery
  • Ibuprofen
  • PAMAM dendrimers

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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