BSA Nanoparticle Loaded Atorvastatin Calcium - A New Facet for an Old Drug

<div><p>Background</p><p>Currently, the discovery of effective chemotherapeutic agents poses a major challenge to the field of cancer biology. The present study focuses on enhancing the therapeutic and anti cancer properties of atorvastatin calcium loaded BSA (ATV-BSA) nanoparticles <i>in vitro</i>.</p><p>Methodology/Results</p><p>BSA-ATV nanoparticles were prepared using desolvation technique. The process parameters were optimized based on the amount of desolvating agent, stabilization conditions as well as the concentration of the cross linker. The anti cancer properties of the protein coated ATV nanoparticles were tested on MiaPaCa-2 cell lines. <i>In vitro</i> release behavior of the drug from the carrier suggests that about 85% of the drug gets released after 72 hrs. Our studies show that ATV-BSA nanoparticles showed specific targeting and enhanced cytotoxicity to MiaPaCa-2 cells when compared to the bare ATV.</p><p>Conclusion</p><p>We hereby propose that the possible mechanism of cellular uptake of albumin bound ATV could be through caveolin mediated endocytosis. Hence our studies open up new facet for an existing cholesterol drug as a potent anti-cancer agent.</p></div

FTIR spectra.

<p>Shows the Fourier Transform Infra Red Spectra of (a) BSA nanoparticles (b) ATV and (c) ATV-BSA nanoparticles in order of their arrangement from top to bottom.</p

ATV release kinetics.

<p><i>In vitro</i> drug release profile at pH 7.4 showing the sustained release of ATV from the nanoparticles at pre defined time intervals.</p

Influence of different ratios of ATV to BSA (20 mg) on Encapsulation Efficiency.

<p>Influence of different ratios of ATV to BSA (20 mg) on Encapsulation Efficiency.</p

Scanning Electron Microscopic images.

<p>Field Emisssion Scanning Electron Microscopic images of (a) BSA nanoparticles (b) ATV-BSA nanoparticles.</p

Propidium Iodide Staining.

<p>Shows the dead cells stained red using propidium iodide upon treatment with ATV and ATV-BSA on MiaPaCa-2 cells.</p

Hemolysis assay.

<p>The biocompatibility of ATV-BSA nanoparticles is shown with tubes from left to right as: PC-Positive control, NC-Negative Control, a to c, d to f and g to i showing the biocompatibility of 10,15 & 20 µg/mL concentrations of ATV, BSA and ATV-BSA nanoparticles in RBC's respectively.</p

Molecular Docking.

<p>Graphical representation of best docking results of BSA-atorvastatin complex using Autodock 4.2. Residual interactions at the BSA-ATV interface in BSA. The symbol coding scheme is as follows. BSA in green color, ATV in blue color. Hydrogen bonding interactions are denoted by dashed lines. Residues involved in the hydrophobic interactions are shown as starbursts.</p

Possible Mechanism.

<p>Schema representing the caveolae mediated endocytosis as possible mechanism involved in the cellular uptake of the ATV-BSA by the cancer cells.</p