In Vitro and In Vivo Anticancer Activity of a Novel Nano-sized Formulation Based on Self-assembling Polymers Against Pancreatic Cancer

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Clare Hoskins (Author) Other; Mehdi Ouaissi (Author) Other; Sofia Costa Lima (Author) Other; Woei Ping Cheng (Author) Other; Ines Loureirio (Author) Other; Eric Mas (Author) Other; Dominique Lombardo (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Ali Ouaissi (Author) Other; Paul Kong Thoo Lin (Author) Other

Journal

Title: Pharmaceutical Research

Vol. 27 No. 12

Pages: 2694-2703

ISSN: 0724-8741

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 18 Citations

ISI Web of Science

Scopus - 24 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

CORDIS: Health sciences

Other information

Authenticus ID: P-003-0S7

DOI: 10.1007/s11095-010-0268-6

Resumo (PT): Purpose To evaluate the in vitro and in vivo pancreatic anticancer activity of a nano-sized formulation based on novel polyallylamine grafted with 5% mole cholesteryl pendant groups (CH5-PAA). Methods Insoluble novel anticancer drug, Bisnaphthalimidopropyldiaaminooctane (BNIPDaoct), was loaded into CH5-PAA polymeric self-assemblies by probe sonication. Hydrodynamic diameters and polydispersity index measurements were determined by photon correlation spectroscopy. The in vitro cytotoxicity evaluation of the formulation was carried out by the sulforhodamine B dye assay with human pancreatic adenocarcinoma BxPC-3 cells, while for the in vivo study, Xenograff mice were used. In vitro apoptotic cell death from the drug formulation was confirmed by flow cytometric analysis. Results The aqueous polymer-drug formulation had a mean hydrodynamic size of 183 nm. The drug aqueous solubility was increased from negligible concentration to 0.3 mg mL−1. CH5-PAA polymer alone did not exhibit cytotoxicity, but the new polymer-drug formulation showed potent in vitro and in vivo anticancer activity. The mode of cell death in the in vitro study was confirmed to be apoptotic. The in vivo results revealed that the CH5-PAA alone did not have any anti-proliferative effect, but the CH5-PAA-drug formulation exhibited similar tumour reduction efficacy as the commercial drug, gemcitabine. Conclusions The proposed formulation shows potential as pancreatic cancer therapeutics. <br> <br> KEY WORDS amphiphilic polyallylamine - apoptosis - Bisnaphthalimidopropyl-diaminooctane - BxPC-3 cells - nanoparticles - pancreatic cancer - self-assembling polymers <br> <a target="_blank" href="http://www.springerlink.com/content/t32n47232v8p76t1/ "> Texto integral </a> <br> <br>

Abstract (EN): To evaluate the in vitro and in vivo pancreatic anticancer activity of a nano-sized formulation based on novel polyallylamine grafted with 5% mole cholesteryl pendant groups (CH(5)-PAA). Insoluble novel anticancer drug, Bisnaphthalimidopropyldiaaminooctane (BNIPDaoct), was loaded into CH(5)-PAA polymeric self-assemblies by probe sonication. Hydrodynamic diameters and polydispersity index measurements were determined by photon correlation spectroscopy. The in vitro cytotoxicity evaluation of the formulation was carried out by the sulforhodamine B dye assay with human pancreatic adenocarcinoma BxPC-3 cells, while for the in vivo study, Xenograff mice were used. In vitro apoptotic cell death from the drug formulation was confirmed by flow cytometric analysis. The aqueous polymer-drug formulation had a mean hydrodynamic size of 183 nm. The drug aqueous solubility was increased from negligible concentration to 0.3 mg mL(-1). CH(5)-PAA polymer alone did not exhibit cytotoxicity, but the new polymer-drug formulation showed potent in vitro and in vivo anticancer activity. The mode of cell death in the in vitro study was confirmed to be apoptotic. The in vivo results revealed that the CH(5)-PAA alone did not have any anti-proliferative effect, but the CH(5)-PAA-drug formulation exhibited similar tumour reduction efficacy as the commercial drug, gemcitabine. The proposed formulation shows potential as pancreatic cancer therapeutics.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10