Friday, October 1, 2010

In Vitro and In Vivo Anticancer Activity of a Novel Nano-sized Formulation Based on Self-assembling Polymers Against Pancreatic Cancer

PurposeTo 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).
MethodsInsoluble 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.
ResultsThe 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.
ConclusionsThe proposed formulation shows potential as pancreatic cancer therapeutics.

1 comment:

jonathan said...

In a given solvent at a particular temperature, as molecular weight increases, the solubility of a polymer decreases.Polymer solubility also provide good information i hope this will also helpful to you all. This same behavior is also noticed as crosslinking degree increases, since strongly crosslinked polymers will inhibit the interaction between polymer chains and solvent molecules, preventing those polymer chains from being transported into solution.* *A similar situation occurs with crystalline macromolecules, although in such a case the dissolution can be forced if an appropriate solvent is available, or warming the polymer up to temperatures slightly below its crystalline melting point (T_m ). For example, highly crystalline linear polyethylene <../../pe.htm> (T_m = 135ºC) can be dissolved in several solvents above 100ºC. Nylon 6.6 <../../nylon.htm> (T_m = 265ºC), a crystalline polymer which is more polar than polyethylene, can be dissolved at room temperature in the presence of solvents with enough ability to interact with its chains, through for example, hydrogen bonding. Branched polymer chains generally increase solubility, although the rate at which this solubility occurs, depends on the particular type of branching. Chains containing long branches, cause dense entanglements making difficult the penetration of solvent molecules. Therefore the rate of dissolution in these cases becomes slower than if it was short branching, where the interaction between chains is practically non-existent