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Pharmaceutical Research

, Volume 32, Issue 4, pp 1249–1263 | Cite as

pH-Responsive Nano Carriers for Doxorubicin Delivery

  • Shahla Bagherifam
  • Frode Miltzow Skjeldal
  • Gareth Griffiths
  • Gunhild M. Mælandsmo
  • Olav Engebråten
  • Bo Nyström
  • Vasif Hasirci
  • Nesrin HasirciEmail author
Research Paper

Abstract

Purpose

The aim of this study was to design stimuli-responsive nanocarriers for anti-cancer drug delivery. For this purpose, doxorubicin (DOX)-loaded, polysebacic anhydride (PSA) based nanocapsules (NC) were combined with pH-sensitive poly (L-histidine) (PLH).

Method

PSA nano-carriers were first loaded with DOX and were coated with poly L-histidine to introduce pH sensitivity. The PLH-coated NCs were then covered with polyethylene glycol (PEG) to reduce macrophage uptake. The drug release profile from this system was examined in two different buffer solutions prepared as acidic (pH5) and physiological (pH 7.4) media. The physical and chemical properties of the nanocapsules were characterized by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), ultraviolet and visible absorption spectroscopy (UV–VIS), and scanning electron microscopy (SEM). In vitro studies of the prepared nanocapsules were conducted in MDA-MB-231 breast cancer cells.

Results

The results obtained by SEM and DLS revealed that nanocapsules have spherical morphology with an average size of 230 nm. Prepared pH sensitive nanocapsules exhibited pH-dependent drug release profile and promising intracellular release of drug. PEGylation of nanoparticles significantly prevented macrophage uptake compared to non-PEGylated particles.

KEY WORDS

doxorubicin nanocapsule pH-responsive poly L-histidine polysebacic anhydride 

ABBREVIATIONS

ATCC

American type culture collection

DAPI

4′,6-diamidino-2-phenylindole

DCM

Dichloromethane

DLS

Dynamic light scattering

DNA

Deoxyribonucleic acid

DOX

Doxorubicin

EE

Encapsulation efficiency

EPR

Enhanced permeability and retention

FDA

Food and drug administration

FTIR

Fourier transform infrared spectroscopy

GPC

Gel permeation chromatography

H-NMR

Proton nuclear magnetic resonance

LC

Loading capacity

MTS

3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium

MW

Molecular weight

NCs

Nanocapsules

PBS

Phosphate buffered saline

PDI

Poly dispersity index

PEG

Polyethylene glycol

PFA

Paraformaldehyde

PLH

Poly (L-histidine)

PLL

Poly L-lysine

PSA

Polysebacic anhydride

PVA

Polyvinyl alcohol

RPMI

Roswell park memorial institute

SEM

Scanning electron microscopy

TPA

12-O-tetradecanoyl-phorbol-13-acetate

UV–VIS

Ultraviolet and visible absorption spectroscopy

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This research was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) with grant No: 111M385. GG and BN were supported by funding from the Norwegian Cancer Society.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Shahla Bagherifam
    • 1
    • 2
  • Frode Miltzow Skjeldal
    • 2
  • Gareth Griffiths
    • 2
  • Gunhild M. Mælandsmo
    • 3
  • Olav Engebråten
    • 3
  • Bo Nyström
    • 4
  • Vasif Hasirci
    • 1
    • 5
    • 6
    • 8
  • Nesrin Hasirci
    • 1
    • 5
    • 7
    • 8
    Email author
  1. 1.Graduate Department of Polymer Science and TechnologyMiddle East Technical UniversityAnkaraTurkey
  2. 2.Institute of Molecular BiosciencesUniversity of OsloOsloNorway
  3. 3.Institute for Cancer Research, Oslo University HospitalUniversity of OsloOsloNorway
  4. 4.Department of ChemistryUniversity of OsloOsloNorway
  5. 5.Graduate Department of BiotechnologyMiddle East Technical UniversityAnkaraTurkey
  6. 6.Department of Biological SciencesMiddle East Technical UniversityAnkaraTurkey
  7. 7.Department of ChemistryMiddle East Technical UniversityAnkaraTurkey
  8. 8.BIOMATEN - Center of Excellence in Biomaterials and Tissue EngineeringMiddle East Technical UniversityAnkaraTurkey

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