In vitro and in vivo anticancer activity of a novel nano-sized formulation based on self-assembling polymers against pancreatic cancer

Clare Hoskins, Mehdi Ouaissi, Sofia Costa Lima, Woei Ping Cheng, Inês Loureirio, Eric Mas, Dominique Lombardo, Anabela Cordeiro-da-Silva, Ali Ouaissi, Paul Kong Thoo Lin

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Abstract

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.
Original languageEnglish
Pages (from-to)2694–2703
Number of pages10
JournalPharmaceutical Research
Volume27
Issue number12
Early online date25 Sep 2010
DOIs
Publication statusPublished - 31 Dec 2010

Keywords

  • pancreatic cancer
  • self-assembling polymers
  • amphiphilic polyallylamine
  • nanoparticles
  • bisnaphthalimidopropyl-diaminooctane
  • apoptosis
  • BxPC-3 cells

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    Hoskins, C., Ouaissi, M., Lima, S. C., Cheng, W. P., Loureirio, I., Mas, E., Lombardo, D., Cordeiro-da-Silva, A., Ouaissi, A., & Kong Thoo Lin, P. (2010). In vitro and in vivo anticancer activity of a novel nano-sized formulation based on self-assembling polymers against pancreatic cancer. Pharmaceutical Research, 27(12), 2694–2703. https://doi.org/10.1007/s11095-010-0268-6