In vitro and in vivo anticancer activity of a novel nano-sized formulation based on self-assembling polymers against pancreatic cancer.
OBJECTIVE
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.
Hoskins
Clare
C
School of Pharmacy and Life Sciences, Robert Gordon University, St. Andrew Street, Aberdeen, Scotland, UK.
Ouaissi
Mehdi
M
Lima
Sofia Costa
SC
Cheng
Woei Ping
WP
Loureirio
Inês
I
Mas
Eric
E
Lombardo
Dominique
D
Cordeiro-da-Silva
Anabela
A
Ouaissi
Ali
A
Kong Thoo Lin
Paul
P
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D051379:Mice; D036103:Nanotechnology; D053644:Naphthalimides / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011108:Polymers; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D053644:Naphthalimides; D011108:Polymers; C557289:bisnaphthalimidopropyldiaaminooctane