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 (CH(5)-PAA). METHODS: 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. 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). 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. CONCLUSIONS: The proposed formulation shows potential as pancreatic cancer therapeutics.
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 (CH(5)-PAA). METHODS: 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 humanpancreatic 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). 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. CONCLUSIONS: The proposed formulation shows potential as pancreatic cancer therapeutics.
Authors: Ayesha Zafar; Lisa I Pilkington; Natalie A Haverkate; Michelle van Rensburg; Euphemia Leung; Sisira Kumara; William A Denny; David Barker; Ali Alsuraifi; Clare Hoskins; Jóhannes Reynisson Journal: Molecules Date: 2018-01-11 Impact factor: 4.411