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pH-Responsive Nano Carriers for Doxorubicin Delivery

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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.

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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

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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.

Author information

Authors and Affiliations

  1. Graduate Department of Polymer Science and Technology, Middle East Technical University, Ankara, Turkey

    Shahla Bagherifam, Vasif Hasirci & Nesrin Hasirci

  2. Institute of Molecular Biosciences, University of Oslo, Oslo, Norway

    Shahla Bagherifam, Frode Miltzow Skjeldal & Gareth Griffiths

  3. Institute for Cancer Research, Oslo University Hospital, University of Oslo, Oslo, Norway

    Gunhild M. Mælandsmo & Olav Engebråten

  4. Department of Chemistry, University of Oslo, Oslo, Norway

    Bo Nyström

  5. Graduate Department of Biotechnology, Middle East Technical University, Ankara, Turkey

    Vasif Hasirci & Nesrin Hasirci

  6. Department of Biological Sciences, Middle East Technical University, Ankara, Turkey

    Vasif Hasirci

  7. Department of Chemistry, Middle East Technical University, Ankara, Turkey

    Nesrin Hasirci

  8. BIOMATEN - Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University, Ankara, 06800, Turkey

    Vasif Hasirci & Nesrin Hasirci

Authors
  1. Shahla Bagherifam
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  2. Frode Miltzow Skjeldal
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Correspondence to Nesrin Hasirci.

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Bagherifam, S., Skjeldal, F.M., Griffiths, G. et al. pH-Responsive Nano Carriers for Doxorubicin Delivery. Pharm Res 32, 1249–1263 (2015). https://doi.org/10.1007/s11095-014-1530-0

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