Iranian Polymer Journal

, Volume 27, Issue 4, pp 263–274 | Cite as

Novel NGR anchored pullulan micelles for controlled and targeted delivery of doxorubicin to HeLa cancerous cells

  • Farshid Hassanzadeh
  • Elahe Mahmoudi
  • Jaleh Varshosaz
  • Ghadam Ali Khodarahmi
  • Mahboubeh Rostami
  • Mostafa Ghanadian
  • Nasim Dana
Original Research


Doxorubicin (DOX) is used to treat different kinds of cancers, including cervix carcinoma. However, it has various side effects such as cardiotoxicity. Nano-sized controlled releasing carriers such as polymeric micelles are of interesting approaches to overcome these side effects of doxorubicin in cancer chemotherapy. Regarding the up-regulation of CD13/APN receptors on the cervix carcinoma cells, which can bind to peptide sequences specially NGR (asparagine–glycine–arginine) with high affinity, peptide sequence (NGR) targeted micelles would lead to effective treatment of this carcinoma. In this study, the NGR peptide sequence was synthesized using the solution-phase strategy from asparagine, glycine, and arginine residues. The pullulan–retinoic acid conjugate and pullulan–retinoic acid–NGR conjugate were prepared by the amide and ester bond formation between the hydroxyl groups of pullulan and carboxylic acid groups of retinoic acid and peptide sequence. Pullulan–retinoic acid–NGR micelles were prepared by the direct dissolution method. The optimized micelles, according to their particle size (124.5 nm), zeta potential (− 3.65 mV), entrapment efficiency (85%), and release of DOX (70%, within 72 h) were assessed for their cytotoxicity on HeLa cells using MTT assay. NGR-targeted pullulan/retinoic acid micelles had higher cytotoxicity than the free DOX in cell culture studies on the HeLa cell line, and this can be a promising result in the treatment of cervix carcinoma.


Aminopeptidase N NGR Pullulan Polymeric micelle Doxorubicin (DOX) Cervix cancer 



We acknowledge the financial support of Novel Drug Delivery Systems Research Center at Isfahan University of Medical Sciences, Grant Number: 293317.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interests.


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Copyright information

© Iran Polymer and Petrochemical Institute 2018

Authors and Affiliations

  1. 1.Novel Drug Delivery Systems Research Centre and Department of Medicinal Chemistry, School of PharmacyIsfahan University of Medical SciencesIsfahanIran
  2. 2.Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran
  3. 3.Novel Drug Delivery Systems Research Center and Department of Pharmaceutics, School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran
  4. 4.Department of Pharmacognosy, School of Pharmacy and Pharmaceutical SciencesIsfahan University of Medical SciencesIsfahanIran
  5. 5.Applied Physiology Research Center, Cardiovascular Research InstituteIsfahan University of Medical SciencesIsfahanIran

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