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

Hoskins, Clare and Ouaissi, Mehdi and Lima, Sofia Costa and Cheng, Woei Ping and Loureirio, Inês and Mas, Eric and Lombardo, Dominique and Cordeiro-da-Silva, Anabela and Ouaissi, Ali and Kong Thoo Lin, Paul (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. ISSN 0724-8741

[thumbnail of Hoskins-etal-PR-2010-In-vitro-and-in-vivo-anticancer-activity-of-a-novel-nano-sized-formulation]
Preview
Text (Hoskins-etal-PR-2010-In-vitro-and-in-vivo-anticancer-activity-of-a-novel-nano-sized-formulation)
Hoskins_etal_PR_2010_In_vitro_and_in_vivo_anticancer_activity_of_a_novel_nano_sized_formulation.pdf
Accepted Author Manuscript

Download (199kB)| Preview

    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.