Mixed poly(vinyl pyrrolidone)-based drug-loaded nanomicelles shows enhanced efficacy against pancreatic cancer cell lines

Anisha Veeren, Archana Bhaw-Luximon, Debabrata Mukhopadhyay, Dhanjay Jhurry

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We report in this paper on the enhanced efficacy of a physical mixture of two single anti-cancer loaded nanomicelles against PANC-1 and BxPC-3. Poly(vinyl pyrrolidone-b-polycaprolactone) (PVP-b-PCL) and poly(vinyl pyrrolidone-b-poly(dioxanone-co-methyl dioxanone)) (PVP-b-P(DX-co-MeDX)) were synthesized and successfully loaded with various anti-cancer drugs - gemcitabine (GEM), doxorubicin.HCl (DOX.HCl), doxorubicin.NH2 (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX). Spherical micelles of size 160–477 nm were obtained as characterized by DLS while sizes determined by TEM were in the range 140–250 nm. The hydrophobic drugs had a higher loading percentage efficiency compared to hydrophilic drugs in the trend PTX > DOX > 5-FU > GEM > DOX.HCl whereas the drug release pattern followed the reverse trend in accordance with decreased polymer-drug interaction as quantified by the binding constant and micellar drug location. Cellular uptake studies showed that nanomicelles are taken up by pancreatic cancer cells into the cytoplasm and nucleus. The free nanomicelles were confirmed to be non-cytotoxic. A physical mixture of GEM loaded micelles and DOX.HCl loaded micelles of comparable size showed significantly higher cytotoxicity than either the free drug mixture or the individual single drug loaded micelles as confirmed by their IC50 values.

Original languageEnglish (US)
Pages (from-to)250-260
Number of pages11
JournalEuropean Journal of Pharmaceutical Sciences
Volume102
DOIs
StatePublished - May 1 2017

Fingerprint

Pyrrolidinones
gemcitabine
Pancreatic Neoplasms
Micelles
Cell Line
Pharmaceutical Preparations
Paclitaxel
Fluorouracil
Doxorubicin
Drug Interactions
Inhibitory Concentration 50
Neoplasms
Polymers
Cytoplasm

Keywords

  • Amphiphilic block copolymers
  • Combined drug delivery
  • Nanocarriers
  • Pancreatic cancer
  • Physically mixed micelles
  • Poly(vinyl pyrrolidone)

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Mixed poly(vinyl pyrrolidone)-based drug-loaded nanomicelles shows enhanced efficacy against pancreatic cancer cell lines. / Veeren, Anisha; Bhaw-Luximon, Archana; Mukhopadhyay, Debabrata; Jhurry, Dhanjay.

In: European Journal of Pharmaceutical Sciences, Vol. 102, 01.05.2017, p. 250-260.

Research output: Contribution to journalArticle

@article{e6b76df4b86f47eb9beadf883fafcccb,
title = "Mixed poly(vinyl pyrrolidone)-based drug-loaded nanomicelles shows enhanced efficacy against pancreatic cancer cell lines",
abstract = "We report in this paper on the enhanced efficacy of a physical mixture of two single anti-cancer loaded nanomicelles against PANC-1 and BxPC-3. Poly(vinyl pyrrolidone-b-polycaprolactone) (PVP-b-PCL) and poly(vinyl pyrrolidone-b-poly(dioxanone-co-methyl dioxanone)) (PVP-b-P(DX-co-MeDX)) were synthesized and successfully loaded with various anti-cancer drugs - gemcitabine (GEM), doxorubicin.HCl (DOX.HCl), doxorubicin.NH2 (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX). Spherical micelles of size 160–477 nm were obtained as characterized by DLS while sizes determined by TEM were in the range 140–250 nm. The hydrophobic drugs had a higher loading percentage efficiency compared to hydrophilic drugs in the trend PTX > DOX > 5-FU > GEM > DOX.HCl whereas the drug release pattern followed the reverse trend in accordance with decreased polymer-drug interaction as quantified by the binding constant and micellar drug location. Cellular uptake studies showed that nanomicelles are taken up by pancreatic cancer cells into the cytoplasm and nucleus. The free nanomicelles were confirmed to be non-cytotoxic. A physical mixture of GEM loaded micelles and DOX.HCl loaded micelles of comparable size showed significantly higher cytotoxicity than either the free drug mixture or the individual single drug loaded micelles as confirmed by their IC50 values.",
keywords = "Amphiphilic block copolymers, Combined drug delivery, Nanocarriers, Pancreatic cancer, Physically mixed micelles, Poly(vinyl pyrrolidone)",
author = "Anisha Veeren and Archana Bhaw-Luximon and Debabrata Mukhopadhyay and Dhanjay Jhurry",
year = "2017",
month = "5",
day = "1",
doi = "10.1016/j.ejps.2017.03.021",
language = "English (US)",
volume = "102",
pages = "250--260",
journal = "European Journal of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "Elsevier",

}

TY - JOUR

T1 - Mixed poly(vinyl pyrrolidone)-based drug-loaded nanomicelles shows enhanced efficacy against pancreatic cancer cell lines

AU - Veeren, Anisha

AU - Bhaw-Luximon, Archana

AU - Mukhopadhyay, Debabrata

AU - Jhurry, Dhanjay

PY - 2017/5/1

Y1 - 2017/5/1

N2 - We report in this paper on the enhanced efficacy of a physical mixture of two single anti-cancer loaded nanomicelles against PANC-1 and BxPC-3. Poly(vinyl pyrrolidone-b-polycaprolactone) (PVP-b-PCL) and poly(vinyl pyrrolidone-b-poly(dioxanone-co-methyl dioxanone)) (PVP-b-P(DX-co-MeDX)) were synthesized and successfully loaded with various anti-cancer drugs - gemcitabine (GEM), doxorubicin.HCl (DOX.HCl), doxorubicin.NH2 (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX). Spherical micelles of size 160–477 nm were obtained as characterized by DLS while sizes determined by TEM were in the range 140–250 nm. The hydrophobic drugs had a higher loading percentage efficiency compared to hydrophilic drugs in the trend PTX > DOX > 5-FU > GEM > DOX.HCl whereas the drug release pattern followed the reverse trend in accordance with decreased polymer-drug interaction as quantified by the binding constant and micellar drug location. Cellular uptake studies showed that nanomicelles are taken up by pancreatic cancer cells into the cytoplasm and nucleus. The free nanomicelles were confirmed to be non-cytotoxic. A physical mixture of GEM loaded micelles and DOX.HCl loaded micelles of comparable size showed significantly higher cytotoxicity than either the free drug mixture or the individual single drug loaded micelles as confirmed by their IC50 values.

AB - We report in this paper on the enhanced efficacy of a physical mixture of two single anti-cancer loaded nanomicelles against PANC-1 and BxPC-3. Poly(vinyl pyrrolidone-b-polycaprolactone) (PVP-b-PCL) and poly(vinyl pyrrolidone-b-poly(dioxanone-co-methyl dioxanone)) (PVP-b-P(DX-co-MeDX)) were synthesized and successfully loaded with various anti-cancer drugs - gemcitabine (GEM), doxorubicin.HCl (DOX.HCl), doxorubicin.NH2 (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX). Spherical micelles of size 160–477 nm were obtained as characterized by DLS while sizes determined by TEM were in the range 140–250 nm. The hydrophobic drugs had a higher loading percentage efficiency compared to hydrophilic drugs in the trend PTX > DOX > 5-FU > GEM > DOX.HCl whereas the drug release pattern followed the reverse trend in accordance with decreased polymer-drug interaction as quantified by the binding constant and micellar drug location. Cellular uptake studies showed that nanomicelles are taken up by pancreatic cancer cells into the cytoplasm and nucleus. The free nanomicelles were confirmed to be non-cytotoxic. A physical mixture of GEM loaded micelles and DOX.HCl loaded micelles of comparable size showed significantly higher cytotoxicity than either the free drug mixture or the individual single drug loaded micelles as confirmed by their IC50 values.

KW - Amphiphilic block copolymers

KW - Combined drug delivery

KW - Nanocarriers

KW - Pancreatic cancer

KW - Physically mixed micelles

KW - Poly(vinyl pyrrolidone)

UR - http://www.scopus.com/inward/record.url?scp=85015757276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85015757276&partnerID=8YFLogxK

U2 - 10.1016/j.ejps.2017.03.021

DO - 10.1016/j.ejps.2017.03.021

M3 - Article

C2 - 28323118

AN - SCOPUS:85015757276

VL - 102

SP - 250

EP - 260

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

ER -