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

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

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.

Citation

HOSKINS, C., OUAISSI, M., LIMA, S.C., CHENG, W.P., LOUREIRIO, I., MAS, E., LOMBARDO, D., CORDEIRO-DA-SILVA, A., OUAISSI, A. and 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 [online], 27(12), pages 2694-2703. Available from: https://doi.org/10.1007/s11095-010-0268-6

• Journal Article Type: Article
• Acceptance Date: Aug 30, 2010
• Online Publication Date: Sep 25, 2010
• Publication Date: Dec 31, 2010
• Deposit Date: Aug 23, 2022
• Publicly Available Date: Sep 12, 2022
• Journal: Pharmaceutical Research
• Print ISSN: 0724-8741
• Electronic ISSN: 1573-904X
• Publisher: American Association of Pharmaceutical Scientists
• Peer Reviewed: Peer Reviewed
• Volume: 27
• Issue: 12
• Pages: 2694-2703
• DOI: https://doi.org/10.1007/s11095-010-0268-6
• Keywords: Amphiphilic polyallylamine; Apoptosis; Bisnaphthalimidopropyl-diaminooctane; BxPC-3 cells; Nanoparticles; Pancreatic cancer; Self-assembling polymers
• Public URL: https://rgu-repository.worktribe.com/output/865522