Grant: Discovery Grants Program - Individual

Biodegradable Chitosan-Protein Nanoparticles as Drug Delivery System: Drug Encapsulation by Water-Soluble Chitosan-Protein Conjugates. Analysis of the Driving Forces Between Drug and Nanocarrier

<p>Nanoparticle therapeutics based on natural and synthetic polymers offer new routes to improve cancer drug delivery with water-soluble polymers aiding in drug solubility, increasing the therapeutic process through long circulation and increasing uptake into tumors by the enhanced permeability and retention effect. Among the natural cationic polymers used in drug delivery systems, chitosan has attracted a major interest in nanomedicine since it is a biocompatible, biodegradable, nontoxic and versatile polymer.</p> <p>Our principal interest in using chitosan and its derivatives as a pharmaceutical carrier is to enhance the bioavailability of therapeutic drugs in vivo. Improving the solubility of chitosan is crucial for the drug-carrier formulation.<br /> <br /> This research seeks to improve chitosan solubility by conjugation with proteins. Chitosan-protein conjugation will increase polymer solubility at physiological pH and will enhance markedly chitosan efficiency, in drug delivery system because most drugs bind effectively to chitosan and protein at neutral pH. In this research proposal, chitosan nanoparticles of different sizes (15, 50, 100 and 200 KDa) will be conjugated with different transporter proteins, such as human and bovine serum albumins and beta-lactoglobulin. Since selected proteins are different in hydrophobicity, chitosan-protein nanocapsules will be more selective towards hydrophilic and hydrophobic drugs. Structural analysis of several anticancer drugs with chitosan-protein nanoparticles will be carried out, using multiple spectroscopic methods combined with a variety of microscopy techniques such as TEM, SEM and AFM images. The effects of polymer size and molecular weight on drug-nanoparticle complexation, the encapsulation efficiency and the release efficacy of each nanocapsule will be evaluated. In addition, we will study in depth the molecular modeling and the thermodynamic analysis of chitosan-protein and its drug-nanocapsules. The generated information will help us to build a fundamental understanding of the most important molecular aspects (i.e., the driving forces behind the non-covalent association between molecules) that dictate the drug encapsulation and release efficiency.<br /> <br /> This proposal will provide an important opportunity to improve chitosan solubility at neutral pH and will facilitate a rational design of chitosan-based drug carriers, that are soluble at physiological pH. The results of this proposal will aid the pharmaceutical industries in developing more effective drug delivery tools based on chitosan-protein nanocarriers. Finally, the multidisciplinary nature of this project will provide major expertise for the HQP, so as to succeed in a highly competitive job market.<br /> <br /> </p>