PEGylated liposomes of anastrozole for long-term treatment of breast cancer

In vitro and in vivo evaluation

Gopal Venkatesh Shavi, Meka Sreenivasa Reddy, Ramesh Raghavendra, Usha Yogendra Nayak, Averineni Ranjith Kumar, Praful Balavant Deshpande, Nayanabhirama Udupa, Gautam Behl, Vivek Dave, Kriti Kushwaha

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The aim of present study was to develop conventional and PEGylated (long circulating), liposomes containing anastrozole (ANS) for effective treatment of breast cancer. ANS is a third-generation non-steroidal aromatase inhibitor of the triazole class used for the treatment of advanced and late-stage breast cancer in post-menopausal women. Under such disease conditions the median duration of therapy should be prolonged until tumor regression ends (>31 months). Liposomes were prepared by the thin film hydration method by using ANS and various lipids such as soyaphosphatidyl choline, cholesterol and methoxy polyethylene glycol distearoyl ethanolamine in different concentration ratios and evaluated for physical characteristics, in vitro drug release and stability. Optimized formulations of liposome were studied for in vitro cytotoxic activity against the BT-549 and MCF-7 cell lines and in vivo behavior in Wistar rats. Preformulation studies, both Fourier transform infrared study and differential scanning calorimetry analysis showed no interaction between the drug and the excipients used in the formulations. The optimized formulations AL-07 and AL-09 liposomes showed encapsulation efficiencies in the range 65.12 ± 1.05% to 69.85 ± 3.2% with desired mean particle size distribution of 101.1 ± 5.9 and 120.2 ± 2.8 nm and zeta potentials of -43.7 ± 4.7 and -62.9 ± 3.5 mV. All the optimized formulations followed Higuchi-matrix release kinetics and when plotted in accordance with the Korsemeyer-Peppas method, the n-value 0.5 < n < 1.0 suggests an anomalous (non-Fickian) transport. Likewise, the PEGylated liposomes showed greater tumor growth inhibition on BT-549 and MCF-7 cell lines from in vitro cytotoxicity studies (p < 0.05). Pharmacokinetic study of conventional and PEGylated liposomes in Wistar rats demonstrated a 3.33- and 20.28-fold increase in AUC(0-∞) values when compared to pure drug (p < 0.001). Among the formulations, PEGylated liposomes showed encouraging results by way of their long circulation and sustained delivery properties for effective treatment of breast cancer.

Original languageEnglish
Pages (from-to)28-46
Number of pages19
JournalJournal of Liposome Research
Volume26
Issue number1
DOIs
Publication statusPublished - 02-01-2016

Fingerprint

Liposomes
Breast Neoplasms
MCF-7 Cells
Therapeutics
Wistar Rats
Drug Stability
Cell Line
Aromatase Inhibitors
Ethanolamine
Triazoles
Excipients
Differential Scanning Calorimetry
Fourier Analysis
Choline
In Vitro Techniques
anastrozole
Drug Interactions
Particle Size
Area Under Curve
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Shavi, Gopal Venkatesh ; Reddy, Meka Sreenivasa ; Raghavendra, Ramesh ; Nayak, Usha Yogendra ; Kumar, Averineni Ranjith ; Deshpande, Praful Balavant ; Udupa, Nayanabhirama ; Behl, Gautam ; Dave, Vivek ; Kushwaha, Kriti. / PEGylated liposomes of anastrozole for long-term treatment of breast cancer : In vitro and in vivo evaluation. In: Journal of Liposome Research. 2016 ; Vol. 26, No. 1. pp. 28-46.
@article{a28f8f7ee1424dda9951f6232e70b324,
title = "PEGylated liposomes of anastrozole for long-term treatment of breast cancer: In vitro and in vivo evaluation",
abstract = "The aim of present study was to develop conventional and PEGylated (long circulating), liposomes containing anastrozole (ANS) for effective treatment of breast cancer. ANS is a third-generation non-steroidal aromatase inhibitor of the triazole class used for the treatment of advanced and late-stage breast cancer in post-menopausal women. Under such disease conditions the median duration of therapy should be prolonged until tumor regression ends (>31 months). Liposomes were prepared by the thin film hydration method by using ANS and various lipids such as soyaphosphatidyl choline, cholesterol and methoxy polyethylene glycol distearoyl ethanolamine in different concentration ratios and evaluated for physical characteristics, in vitro drug release and stability. Optimized formulations of liposome were studied for in vitro cytotoxic activity against the BT-549 and MCF-7 cell lines and in vivo behavior in Wistar rats. Preformulation studies, both Fourier transform infrared study and differential scanning calorimetry analysis showed no interaction between the drug and the excipients used in the formulations. The optimized formulations AL-07 and AL-09 liposomes showed encapsulation efficiencies in the range 65.12 ± 1.05{\%} to 69.85 ± 3.2{\%} with desired mean particle size distribution of 101.1 ± 5.9 and 120.2 ± 2.8 nm and zeta potentials of -43.7 ± 4.7 and -62.9 ± 3.5 mV. All the optimized formulations followed Higuchi-matrix release kinetics and when plotted in accordance with the Korsemeyer-Peppas method, the n-value 0.5 < n < 1.0 suggests an anomalous (non-Fickian) transport. Likewise, the PEGylated liposomes showed greater tumor growth inhibition on BT-549 and MCF-7 cell lines from in vitro cytotoxicity studies (p < 0.05). Pharmacokinetic study of conventional and PEGylated liposomes in Wistar rats demonstrated a 3.33- and 20.28-fold increase in AUC(0-∞) values when compared to pure drug (p < 0.001). Among the formulations, PEGylated liposomes showed encouraging results by way of their long circulation and sustained delivery properties for effective treatment of breast cancer.",
author = "Shavi, {Gopal Venkatesh} and Reddy, {Meka Sreenivasa} and Ramesh Raghavendra and Nayak, {Usha Yogendra} and Kumar, {Averineni Ranjith} and Deshpande, {Praful Balavant} and Nayanabhirama Udupa and Gautam Behl and Vivek Dave and Kriti Kushwaha",
year = "2016",
month = "1",
day = "2",
doi = "10.3109/08982104.2015.1029493",
language = "English",
volume = "26",
pages = "28--46",
journal = "Journal of Liposome Research",
issn = "0898-2104",
publisher = "Informa Healthcare",
number = "1",

}

PEGylated liposomes of anastrozole for long-term treatment of breast cancer : In vitro and in vivo evaluation. / Shavi, Gopal Venkatesh; Reddy, Meka Sreenivasa; Raghavendra, Ramesh; Nayak, Usha Yogendra; Kumar, Averineni Ranjith; Deshpande, Praful Balavant; Udupa, Nayanabhirama; Behl, Gautam; Dave, Vivek; Kushwaha, Kriti.

In: Journal of Liposome Research, Vol. 26, No. 1, 02.01.2016, p. 28-46.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PEGylated liposomes of anastrozole for long-term treatment of breast cancer

T2 - In vitro and in vivo evaluation

AU - Shavi, Gopal Venkatesh

AU - Reddy, Meka Sreenivasa

AU - Raghavendra, Ramesh

AU - Nayak, Usha Yogendra

AU - Kumar, Averineni Ranjith

AU - Deshpande, Praful Balavant

AU - Udupa, Nayanabhirama

AU - Behl, Gautam

AU - Dave, Vivek

AU - Kushwaha, Kriti

PY - 2016/1/2

Y1 - 2016/1/2

N2 - The aim of present study was to develop conventional and PEGylated (long circulating), liposomes containing anastrozole (ANS) for effective treatment of breast cancer. ANS is a third-generation non-steroidal aromatase inhibitor of the triazole class used for the treatment of advanced and late-stage breast cancer in post-menopausal women. Under such disease conditions the median duration of therapy should be prolonged until tumor regression ends (>31 months). Liposomes were prepared by the thin film hydration method by using ANS and various lipids such as soyaphosphatidyl choline, cholesterol and methoxy polyethylene glycol distearoyl ethanolamine in different concentration ratios and evaluated for physical characteristics, in vitro drug release and stability. Optimized formulations of liposome were studied for in vitro cytotoxic activity against the BT-549 and MCF-7 cell lines and in vivo behavior in Wistar rats. Preformulation studies, both Fourier transform infrared study and differential scanning calorimetry analysis showed no interaction between the drug and the excipients used in the formulations. The optimized formulations AL-07 and AL-09 liposomes showed encapsulation efficiencies in the range 65.12 ± 1.05% to 69.85 ± 3.2% with desired mean particle size distribution of 101.1 ± 5.9 and 120.2 ± 2.8 nm and zeta potentials of -43.7 ± 4.7 and -62.9 ± 3.5 mV. All the optimized formulations followed Higuchi-matrix release kinetics and when plotted in accordance with the Korsemeyer-Peppas method, the n-value 0.5 < n < 1.0 suggests an anomalous (non-Fickian) transport. Likewise, the PEGylated liposomes showed greater tumor growth inhibition on BT-549 and MCF-7 cell lines from in vitro cytotoxicity studies (p < 0.05). Pharmacokinetic study of conventional and PEGylated liposomes in Wistar rats demonstrated a 3.33- and 20.28-fold increase in AUC(0-∞) values when compared to pure drug (p < 0.001). Among the formulations, PEGylated liposomes showed encouraging results by way of their long circulation and sustained delivery properties for effective treatment of breast cancer.

AB - The aim of present study was to develop conventional and PEGylated (long circulating), liposomes containing anastrozole (ANS) for effective treatment of breast cancer. ANS is a third-generation non-steroidal aromatase inhibitor of the triazole class used for the treatment of advanced and late-stage breast cancer in post-menopausal women. Under such disease conditions the median duration of therapy should be prolonged until tumor regression ends (>31 months). Liposomes were prepared by the thin film hydration method by using ANS and various lipids such as soyaphosphatidyl choline, cholesterol and methoxy polyethylene glycol distearoyl ethanolamine in different concentration ratios and evaluated for physical characteristics, in vitro drug release and stability. Optimized formulations of liposome were studied for in vitro cytotoxic activity against the BT-549 and MCF-7 cell lines and in vivo behavior in Wistar rats. Preformulation studies, both Fourier transform infrared study and differential scanning calorimetry analysis showed no interaction between the drug and the excipients used in the formulations. The optimized formulations AL-07 and AL-09 liposomes showed encapsulation efficiencies in the range 65.12 ± 1.05% to 69.85 ± 3.2% with desired mean particle size distribution of 101.1 ± 5.9 and 120.2 ± 2.8 nm and zeta potentials of -43.7 ± 4.7 and -62.9 ± 3.5 mV. All the optimized formulations followed Higuchi-matrix release kinetics and when plotted in accordance with the Korsemeyer-Peppas method, the n-value 0.5 < n < 1.0 suggests an anomalous (non-Fickian) transport. Likewise, the PEGylated liposomes showed greater tumor growth inhibition on BT-549 and MCF-7 cell lines from in vitro cytotoxicity studies (p < 0.05). Pharmacokinetic study of conventional and PEGylated liposomes in Wistar rats demonstrated a 3.33- and 20.28-fold increase in AUC(0-∞) values when compared to pure drug (p < 0.001). Among the formulations, PEGylated liposomes showed encouraging results by way of their long circulation and sustained delivery properties for effective treatment of breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=84955308172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955308172&partnerID=8YFLogxK

U2 - 10.3109/08982104.2015.1029493

DO - 10.3109/08982104.2015.1029493

M3 - Article

VL - 26

SP - 28

EP - 46

JO - Journal of Liposome Research

JF - Journal of Liposome Research

SN - 0898-2104

IS - 1

ER -