Preparation, characterisation and preliminary antitumour activity evaluation of a novel nanoparticulate system based on a cisplatin-hyaluronate complex and N-trimethyl chitosan

Sergio Cafaggi, Eleonora Russo, Rossana Stefani, Brunella Parodi, Gabriele Caviglioli, Greta Sillo, Angela Bisio, Cinzia Aiello, Maurizio Viale

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In this work, nanoparticles with a positive surface charge were prepared through the electrostatic interaction of a new cisplatin-hyaluronate complex with N-trimethyl chitosan (substitution degree of 85%). Mean particle diameter was approximately 195 nm. Drug loading of nanoparticles, which had a zeta potential of about 27 mV, was equal to 6% w/w. After 24 h, while the cisplatin-hyaluronate complex released approximately 60% w/w drug in phosphate buffered saline at pH 7.4, approximately 40% w/w of total cisplatin was released from nanoparticles. The same cumulative amounts of released drug were found after 48 h. These nanoparticles, as well as the starting cisplatin-hyaluronate complex, were active on all cell lines tested (P388, A2780, A549), with an antiproliferative activity similar to that of cisplatin. Apoptosis was markedly induced in A2780 cells by nanoparticles. In a preliminary in vivo experiment, the antitumour activity against a murine tumour (P388 cells) subcutaneously implanted in mice, resulted similar to that of cisplatin for nanoparticles whereas the starting complex showed a non-significant activity at the cisplatin dose tested. Body weight change of treated mice suggested a significantly better tolerance of the nanoparticles compared to cisplatin, after an initial brief period of acute toxicity higher than the parent drug. These results indicate that such a particulate system could be useful as a carrier for cisplatin delivery.

Original languageEnglish
Pages (from-to)443-455
Number of pages13
JournalInvestigational New Drugs
Volume29
Issue number3
DOIs
Publication statusPublished - Jun 2011

Fingerprint

Cisplatin
Nanoparticles
Pharmaceutical Preparations
N-trimethyl chitosan chloride
Body Weight Changes
Static Electricity
Phosphates
Apoptosis
Cell Line
Neoplasms

Keywords

  • Antiproliferative activity
  • Antitumour activity
  • Cisplatin
  • Hyaluronic acid/hyaluronan
  • Nanoparticle
  • Quaternised chitosan

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

Preparation, characterisation and preliminary antitumour activity evaluation of a novel nanoparticulate system based on a cisplatin-hyaluronate complex and N-trimethyl chitosan. / Cafaggi, Sergio; Russo, Eleonora; Stefani, Rossana; Parodi, Brunella; Caviglioli, Gabriele; Sillo, Greta; Bisio, Angela; Aiello, Cinzia; Viale, Maurizio.

In: Investigational New Drugs, Vol. 29, No. 3, 06.2011, p. 443-455.

Research output: Contribution to journalArticle

Cafaggi, Sergio ; Russo, Eleonora ; Stefani, Rossana ; Parodi, Brunella ; Caviglioli, Gabriele ; Sillo, Greta ; Bisio, Angela ; Aiello, Cinzia ; Viale, Maurizio. / Preparation, characterisation and preliminary antitumour activity evaluation of a novel nanoparticulate system based on a cisplatin-hyaluronate complex and N-trimethyl chitosan. In: Investigational New Drugs. 2011 ; Vol. 29, No. 3. pp. 443-455.
@article{a7ac0998bc5344d1bbf0fdb4dd3590dc,
title = "Preparation, characterisation and preliminary antitumour activity evaluation of a novel nanoparticulate system based on a cisplatin-hyaluronate complex and N-trimethyl chitosan",
abstract = "In this work, nanoparticles with a positive surface charge were prepared through the electrostatic interaction of a new cisplatin-hyaluronate complex with N-trimethyl chitosan (substitution degree of 85{\%}). Mean particle diameter was approximately 195 nm. Drug loading of nanoparticles, which had a zeta potential of about 27 mV, was equal to 6{\%} w/w. After 24 h, while the cisplatin-hyaluronate complex released approximately 60{\%} w/w drug in phosphate buffered saline at pH 7.4, approximately 40{\%} w/w of total cisplatin was released from nanoparticles. The same cumulative amounts of released drug were found after 48 h. These nanoparticles, as well as the starting cisplatin-hyaluronate complex, were active on all cell lines tested (P388, A2780, A549), with an antiproliferative activity similar to that of cisplatin. Apoptosis was markedly induced in A2780 cells by nanoparticles. In a preliminary in vivo experiment, the antitumour activity against a murine tumour (P388 cells) subcutaneously implanted in mice, resulted similar to that of cisplatin for nanoparticles whereas the starting complex showed a non-significant activity at the cisplatin dose tested. Body weight change of treated mice suggested a significantly better tolerance of the nanoparticles compared to cisplatin, after an initial brief period of acute toxicity higher than the parent drug. These results indicate that such a particulate system could be useful as a carrier for cisplatin delivery.",
keywords = "Antiproliferative activity, Antitumour activity, Cisplatin, Hyaluronic acid/hyaluronan, Nanoparticle, Quaternised chitosan",
author = "Sergio Cafaggi and Eleonora Russo and Rossana Stefani and Brunella Parodi and Gabriele Caviglioli and Greta Sillo and Angela Bisio and Cinzia Aiello and Maurizio Viale",
year = "2011",
month = "6",
doi = "10.1007/s10637-009-9373-y",
language = "English",
volume = "29",
pages = "443--455",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "3",

}

TY - JOUR

T1 - Preparation, characterisation and preliminary antitumour activity evaluation of a novel nanoparticulate system based on a cisplatin-hyaluronate complex and N-trimethyl chitosan

AU - Cafaggi, Sergio

AU - Russo, Eleonora

AU - Stefani, Rossana

AU - Parodi, Brunella

AU - Caviglioli, Gabriele

AU - Sillo, Greta

AU - Bisio, Angela

AU - Aiello, Cinzia

AU - Viale, Maurizio

PY - 2011/6

Y1 - 2011/6

N2 - In this work, nanoparticles with a positive surface charge were prepared through the electrostatic interaction of a new cisplatin-hyaluronate complex with N-trimethyl chitosan (substitution degree of 85%). Mean particle diameter was approximately 195 nm. Drug loading of nanoparticles, which had a zeta potential of about 27 mV, was equal to 6% w/w. After 24 h, while the cisplatin-hyaluronate complex released approximately 60% w/w drug in phosphate buffered saline at pH 7.4, approximately 40% w/w of total cisplatin was released from nanoparticles. The same cumulative amounts of released drug were found after 48 h. These nanoparticles, as well as the starting cisplatin-hyaluronate complex, were active on all cell lines tested (P388, A2780, A549), with an antiproliferative activity similar to that of cisplatin. Apoptosis was markedly induced in A2780 cells by nanoparticles. In a preliminary in vivo experiment, the antitumour activity against a murine tumour (P388 cells) subcutaneously implanted in mice, resulted similar to that of cisplatin for nanoparticles whereas the starting complex showed a non-significant activity at the cisplatin dose tested. Body weight change of treated mice suggested a significantly better tolerance of the nanoparticles compared to cisplatin, after an initial brief period of acute toxicity higher than the parent drug. These results indicate that such a particulate system could be useful as a carrier for cisplatin delivery.

AB - In this work, nanoparticles with a positive surface charge were prepared through the electrostatic interaction of a new cisplatin-hyaluronate complex with N-trimethyl chitosan (substitution degree of 85%). Mean particle diameter was approximately 195 nm. Drug loading of nanoparticles, which had a zeta potential of about 27 mV, was equal to 6% w/w. After 24 h, while the cisplatin-hyaluronate complex released approximately 60% w/w drug in phosphate buffered saline at pH 7.4, approximately 40% w/w of total cisplatin was released from nanoparticles. The same cumulative amounts of released drug were found after 48 h. These nanoparticles, as well as the starting cisplatin-hyaluronate complex, were active on all cell lines tested (P388, A2780, A549), with an antiproliferative activity similar to that of cisplatin. Apoptosis was markedly induced in A2780 cells by nanoparticles. In a preliminary in vivo experiment, the antitumour activity against a murine tumour (P388 cells) subcutaneously implanted in mice, resulted similar to that of cisplatin for nanoparticles whereas the starting complex showed a non-significant activity at the cisplatin dose tested. Body weight change of treated mice suggested a significantly better tolerance of the nanoparticles compared to cisplatin, after an initial brief period of acute toxicity higher than the parent drug. These results indicate that such a particulate system could be useful as a carrier for cisplatin delivery.

KW - Antiproliferative activity

KW - Antitumour activity

KW - Cisplatin

KW - Hyaluronic acid/hyaluronan

KW - Nanoparticle

KW - Quaternised chitosan

UR - http://www.scopus.com/inward/record.url?scp=79955575116&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955575116&partnerID=8YFLogxK

U2 - 10.1007/s10637-009-9373-y

DO - 10.1007/s10637-009-9373-y

M3 - Article

VL - 29

SP - 443

EP - 455

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 3

ER -