PEGylated PAMAM dendrimers

Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery

Duy Luong, Prashant Kesharwani, Rahul Deshmukh, Mohd Cairul Iqbal Mohd Amin, Umesh Gupta, Khaled Greish, Arun K. Iyer

Research output: Contribution to journalReview article

95 Citations (Scopus)

Abstract

Poly(amidoamine) dendrimers (PAMAM) are well-defined, highly branched, nanoscale macromolecules with numerous active amine groups on the surface. PAMAM dendrimer can enhance the solubility of hydrophobic drugs, and with numerous reactive groups on the surface PAMAM dendrimer can be engineered with various functional groups for specific targeting ability. However, in physiological conditions, these amine groups are toxic to cells and limit the application of PAMAM. In the recent years, polyethylene glycol (PEG) conjugation has been the most widely used approach to reduce the toxicity of the active group on dendrimer surface. PEG molecules are known to be inert, non-immunogenic, and non-antigenic with a significant water solubility. PEGylated PAMAM-mediated delivery could not only overcome the limitations of dendrimer such as drug leakage, immunogenicity, hemolytic toxicity, systemic cytotoxicity but they also have the ability to enhance the solubilization of hydrophobic drugs and facilitates the potential for DNA transfection, siRNA delivery and tumor targeting. This review focuses on the recent developments on the application and influence of PEGylation on various biopharmaceutical properties of PAMAM dendrimers. Statement of Significance It is well established that dendrimers have demonstrated promising potentials for drug delivery. However, the inherent toxicity poses challenges for its clinical translation. In this regard, PEGylation has helped mitigate some of the toxicity concerns of dendrimers and have paved the way forward for testing its translational potentials. The review is a collection of articles demonstrating the utility of PEGylation of the most studied PAMAM dendrimers. To our knowledge, this is a first such attempt to draw reader's attention, specifically, towards PEGylated PAMAM dendrimers.

Original languageEnglish
Pages (from-to)14-29
Number of pages16
JournalActa Biomaterialia
Volume43
DOIs
Publication statusPublished - 1 Oct 2016

Fingerprint

Dendrimers
Toxicity
Genes
Pharmaceutical Preparations
Solubility
Amines
Poisons
Polyethylene glycols
Cytotoxicity
Macromolecules
Drug delivery
Functional groups
Small Interfering RNA
Transfection
PAMAM Starburst
Tumors
Molecules
Water
DNA
Testing

Keywords

  • Dendrimer toxicity
  • Drug delivery
  • Gene delivery
  • PAMAM dendrimer
  • PEGylation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering
  • Molecular Biology

Cite this

PEGylated PAMAM dendrimers : Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery. / Luong, Duy; Kesharwani, Prashant; Deshmukh, Rahul; Mohd Amin, Mohd Cairul Iqbal; Gupta, Umesh; Greish, Khaled; Iyer, Arun K.

In: Acta Biomaterialia, Vol. 43, 01.10.2016, p. 14-29.

Research output: Contribution to journalReview article

Luong, Duy ; Kesharwani, Prashant ; Deshmukh, Rahul ; Mohd Amin, Mohd Cairul Iqbal ; Gupta, Umesh ; Greish, Khaled ; Iyer, Arun K. / PEGylated PAMAM dendrimers : Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery. In: Acta Biomaterialia. 2016 ; Vol. 43. pp. 14-29.
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