Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery

Bhavani Miryala, Sudhakar Godeshala, Taraka Sai Pavan Grandhi, Matthew D. Christensen, Yanqing Tian, Kaushal Rege

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic nanoparticles for drug delivery, with an eye towards ablation of cancer cells. The aminoglycoside paromomycin was first cross-linked with resorcinol diglycidyl ether leading to the formation of a poly (amino ether), PAE. PAE molecules were further derivatized with methoxy-terminated poly(ethylene glycol) or mPEG resulting in the formation of mPEG-PAE polymer, which self-assembled to form nanoparticles. Formation of the mPEG-PAE amphiphile was characterized using 1H NMR, 13C NMR, gel permeation chromatography (GPC) and FTIR spectroscopy. Self-assembly of the polymer into nanoparticles was characterized using dynamic light scattering, zeta potential analyses, atomic force microscopy (AFM) and the pyrene fluorescence assay. mPEG-PAE nanoparticles were able to carry significant amounts of doxorubicin (DOX), presumably by means of hydrophobic interactions between the drug and the core. Cell-based studies indicated that mPEG-PAE nanoparticles, loaded with doxorubicin, were able to induce significant loss in viabilities of PC3 human prostate cancer, MDA-MB-231 human breast cancer, and MB49 murine bladder cancer cells; empty nanoparticles resulted in negligible losses of cell viability under the conditions investigated. Taken together, our results indicate that the mPEG-PAE nanoparticle platform is attractive for drug delivery in different applications, including cancer.

Original languageEnglish (US)
Pages (from-to)924-937
Number of pages14
JournalColloids and Surfaces B: Biointerfaces
Volume146
DOIs
StatePublished - Oct 1 2016

Fingerprint

Aminoglycosides
Nanoparticles
delivery
nanoparticles
cancer
drugs
Cells
Drug delivery
viability
Doxorubicin
Ethers
ethers
Polymers
Nuclear magnetic resonance
Paromomycin
Pharmaceutical Preparations
multiple docking adapters
nuclear magnetic resonance
Amphiphiles
Drug Carriers

Keywords

  • Doxorubicin
  • Drug delivery
  • Nanoparticles
  • Paromomycin

ASJC Scopus subject areas

  • Biotechnology
  • Colloid and Surface Chemistry
  • Physical and Theoretical Chemistry
  • Surfaces and Interfaces

Cite this

Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery. / Miryala, Bhavani; Godeshala, Sudhakar; Grandhi, Taraka Sai Pavan; Christensen, Matthew D.; Tian, Yanqing; Rege, Kaushal.

In: Colloids and Surfaces B: Biointerfaces, Vol. 146, 01.10.2016, p. 924-937.

Research output: Contribution to journalArticle

Miryala, Bhavani ; Godeshala, Sudhakar ; Grandhi, Taraka Sai Pavan ; Christensen, Matthew D. ; Tian, Yanqing ; Rege, Kaushal. / Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery. In: Colloids and Surfaces B: Biointerfaces. 2016 ; Vol. 146. pp. 924-937.
@article{2b42e4ea45044247b2afa4ce19884f5b,
title = "Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery",
abstract = "The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic nanoparticles for drug delivery, with an eye towards ablation of cancer cells. The aminoglycoside paromomycin was first cross-linked with resorcinol diglycidyl ether leading to the formation of a poly (amino ether), PAE. PAE molecules were further derivatized with methoxy-terminated poly(ethylene glycol) or mPEG resulting in the formation of mPEG-PAE polymer, which self-assembled to form nanoparticles. Formation of the mPEG-PAE amphiphile was characterized using 1H NMR, 13C NMR, gel permeation chromatography (GPC) and FTIR spectroscopy. Self-assembly of the polymer into nanoparticles was characterized using dynamic light scattering, zeta potential analyses, atomic force microscopy (AFM) and the pyrene fluorescence assay. mPEG-PAE nanoparticles were able to carry significant amounts of doxorubicin (DOX), presumably by means of hydrophobic interactions between the drug and the core. Cell-based studies indicated that mPEG-PAE nanoparticles, loaded with doxorubicin, were able to induce significant loss in viabilities of PC3 human prostate cancer, MDA-MB-231 human breast cancer, and MB49 murine bladder cancer cells; empty nanoparticles resulted in negligible losses of cell viability under the conditions investigated. Taken together, our results indicate that the mPEG-PAE nanoparticle platform is attractive for drug delivery in different applications, including cancer.",
keywords = "Doxorubicin, Drug delivery, Nanoparticles, Paromomycin",
author = "Bhavani Miryala and Sudhakar Godeshala and Grandhi, {Taraka Sai Pavan} and Christensen, {Matthew D.} and Yanqing Tian and Kaushal Rege",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.colsurfb.2016.06.028",
language = "English (US)",
volume = "146",
pages = "924--937",
journal = "Colloids and Surfaces B: Biointerfaces",
issn = "0927-7765",
publisher = "Elsevier",

}

TY - JOUR

T1 - Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery

AU - Miryala, Bhavani

AU - Godeshala, Sudhakar

AU - Grandhi, Taraka Sai Pavan

AU - Christensen, Matthew D.

AU - Tian, Yanqing

AU - Rege, Kaushal

PY - 2016/10/1

Y1 - 2016/10/1

N2 - The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic nanoparticles for drug delivery, with an eye towards ablation of cancer cells. The aminoglycoside paromomycin was first cross-linked with resorcinol diglycidyl ether leading to the formation of a poly (amino ether), PAE. PAE molecules were further derivatized with methoxy-terminated poly(ethylene glycol) or mPEG resulting in the formation of mPEG-PAE polymer, which self-assembled to form nanoparticles. Formation of the mPEG-PAE amphiphile was characterized using 1H NMR, 13C NMR, gel permeation chromatography (GPC) and FTIR spectroscopy. Self-assembly of the polymer into nanoparticles was characterized using dynamic light scattering, zeta potential analyses, atomic force microscopy (AFM) and the pyrene fluorescence assay. mPEG-PAE nanoparticles were able to carry significant amounts of doxorubicin (DOX), presumably by means of hydrophobic interactions between the drug and the core. Cell-based studies indicated that mPEG-PAE nanoparticles, loaded with doxorubicin, were able to induce significant loss in viabilities of PC3 human prostate cancer, MDA-MB-231 human breast cancer, and MB49 murine bladder cancer cells; empty nanoparticles resulted in negligible losses of cell viability under the conditions investigated. Taken together, our results indicate that the mPEG-PAE nanoparticle platform is attractive for drug delivery in different applications, including cancer.

AB - The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic nanoparticles for drug delivery, with an eye towards ablation of cancer cells. The aminoglycoside paromomycin was first cross-linked with resorcinol diglycidyl ether leading to the formation of a poly (amino ether), PAE. PAE molecules were further derivatized with methoxy-terminated poly(ethylene glycol) or mPEG resulting in the formation of mPEG-PAE polymer, which self-assembled to form nanoparticles. Formation of the mPEG-PAE amphiphile was characterized using 1H NMR, 13C NMR, gel permeation chromatography (GPC) and FTIR spectroscopy. Self-assembly of the polymer into nanoparticles was characterized using dynamic light scattering, zeta potential analyses, atomic force microscopy (AFM) and the pyrene fluorescence assay. mPEG-PAE nanoparticles were able to carry significant amounts of doxorubicin (DOX), presumably by means of hydrophobic interactions between the drug and the core. Cell-based studies indicated that mPEG-PAE nanoparticles, loaded with doxorubicin, were able to induce significant loss in viabilities of PC3 human prostate cancer, MDA-MB-231 human breast cancer, and MB49 murine bladder cancer cells; empty nanoparticles resulted in negligible losses of cell viability under the conditions investigated. Taken together, our results indicate that the mPEG-PAE nanoparticle platform is attractive for drug delivery in different applications, including cancer.

KW - Doxorubicin

KW - Drug delivery

KW - Nanoparticles

KW - Paromomycin

UR - http://www.scopus.com/inward/record.url?scp=84979574645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979574645&partnerID=8YFLogxK

U2 - 10.1016/j.colsurfb.2016.06.028

DO - 10.1016/j.colsurfb.2016.06.028

M3 - Article

C2 - 27472455

AN - SCOPUS:84979574645

VL - 146

SP - 924

EP - 937

JO - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

SN - 0927-7765

ER -