Controlled release of doxorubicin from polyethylene glycol functionalized melanin nanoparticles for breast cancer therapy: Part I. Production and drug release performance of the melanin nanoparticles

Busra Ozlu; Gozde Kabay; Ilyas Bocek; Merve Yilmaz; Ayse Kevser Piskin; Bong Sup Shim; Mehmet Mutlu

doi:10.1016/j.ijpharm.2019.118613

Controlled release of doxorubicin from polyethylene glycol functionalized melanin nanoparticles for breast cancer therapy: Part I. Production and drug release performance of the melanin nanoparticles

Int J Pharm. 2019 Oct 30:570:118613. doi: 10.1016/j.ijpharm.2019.118613. Epub 2019 Aug 12.

Authors

Busra Ozlu¹, Gozde Kabay², Ilyas Bocek³, Merve Yilmaz⁴, Ayse Kevser Piskin⁴, Bong Sup Shim⁵, Mehmet Mutlu⁶

Affiliations

¹ Plasma Aided Biomedical Research Group (pabmed), Department of Biomedical Engineering, Graduate School of Science and Technology, TOBB University of Economics and Technology, Ankara 06560, Turkey; Department of Chemical Engineering, Inha University, Incheon 22212, South Korea.
² Plasma Aided Biomedical Research Group (pabmed), Department of Biomedical Engineering, Graduate School of Science and Technology, TOBB University of Economics and Technology, Ankara 06560, Turkey; Department of Biological Systems Engineering, University of Wisconsin-Madison, Madison 53706, WI, USA.
³ Plasma Aided Biomedical Research Group (pabmed), Department of Biomedical Department, TOBB University of Economics and Technology, Ankara 06560, Turkey.
⁴ Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
⁵ Department of Chemical Engineering, Inha University, Incheon 22212, South Korea.
⁶ Plasma Aided Biomedical Research Group (pabmed), Department of Biomedical Department, TOBB University of Economics and Technology, Ankara 06560, Turkey. Electronic address: m.mutlu@etu.edu.tr.

PMID: 31415880
DOI: 10.1016/j.ijpharm.2019.118613

Abstract

In this study, polyethylene glycol (PEG) conjugated melanin nanoparticles (MNPs) were prepared (PEG-MNPs). A model chemotherapy drug, doxorubicin (DOX), was loaded into the PEG-MNPs with varied concentrations (0.125, 0.250, 0.500 mg/mL). TEM images showed that, DOX-PEG-MNPs are spherical-shaped and 15 ± 2.2 nm in diameter. FTIR spectroscopy analysis demonstrated that MNPs were successfully modified with PEG. The UV-Vis spectroscopy results showed that the drug loading capacity of MNPs was 0.7 mg/ml of DOX in 2 mg/ml of PEG-MNPs. The time course data showed that, the release behavior of DOX from MNPs was primarily diffusion controlled. In vitro cytotoxicity assays demonstrated that MNP and PEG-MNP did not show any toxic effect on mouse fibroblast cells while DOX-PEG-MNP was able to inhibit the proliferation of human breast cancer cells. The results confirm that the application area of MNPs in controlled and prolonged drug release could be extended to the different types of cancer therapeutics.

Keywords: Breast cancer; Controlled release; Doxorubicin; Melanin nanoparticle; Nano-sized drug delivery.

MeSH terms

Animals
Breast Neoplasms / drug therapy*
Cell Line
Cell Line, Tumor
Cell Survival / drug effects
Delayed-Action Preparations / chemistry*
Delayed-Action Preparations / pharmacology
Doxorubicin / chemistry*
Doxorubicin / pharmacology*
Drug Carriers / chemistry
Drug Delivery Systems / methods
Drug Liberation / drug effects
Female
Humans
Melanins / chemistry*
Mice
Nanoparticles / chemistry*
Polyethylene Glycols / chemistry*

Substances

Delayed-Action Preparations
Drug Carriers
Melanins
Polyethylene Glycols
Doxorubicin