Nanoscale Functionalities for Targeted Drug Delivery of Biopharmaceutics

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Constantinos M. Paleos







The present proposal aims at the development of innovative multidisciplinary approaches for the design, synthesis and evaluation of molecular, nano- and micro-scale functionalities for targeted delivery of therapeutic peptides and proteins (biopharmaceutics). New protein- and peptide-based drugs are being discovered every day and their increased availability offers new ways to treat diseases. However, the structure, physicochemical properties, stability, pharmacodynamics, and pharmacokinetics of these new biopharmaceutics place stringent demands on the way they are delivered into the body. Carrier-based drug delivery systems can improve the bioavailability and diminish the toxicity of Peptidic/Proteinic (P/P) drugs. Furthermore, the carrier specificity can be enhanced, through proper functionalization, and the release of the therapeutic peptide/protein can be controlled on demand. Artificial nanostructures being of the same size as biological entities, can readily interact with biomolecules both on the cell’s surface and within the cell. Thus, the development of functionalized nanocarriers and nanoparticle-based microcarriers for P/P delivery is both an important scientific challenge and potentially a business breakthrough for the biopharmaceutical industry. The present IP will be focused on the development of functionalized nanocarriers for the treatment of various diseases based on targeted, controlled delivery of P/P drugs. More specifically, the IP will address the following topics: 

Diseases: Neurodegenerative diseases such as Alzheimers’, chronic pulmonary diseases, diabetes, hematopoesis, cancer and infections. 

Therapeutic Proteins/Peptides: Vasoactive intestinal peptide, nerve growth factor, activity-dependent neurotrophic factor, non-hematopoetic and hematopoetic EPO-mimetics, insulin, germin-like protein, endostatin, vaccines. 

Nanocarriers: Nanoscale polymer-P/P complexes and nanoparticles in the form of micelles, pegylated liposomes, organic/inorganic nanocomposites consisting of biodegradable polymers, block or graft copolymers, polyelectrolytes, thiomers, bioconjugates and hydrogels. 

Administration Routes: Oral, pulmonary and brain targeting. 

Nanocarriers Specifications: Biocompatibility, biodegradability, low toxicity, stability, targeting and stimuli responsive properties and controlled drug release kinetics. 

More specifically, the present IP aims at the following scientific and technological objectives: 

• Design, synthesis and functionalization of novel nanocarriers and nanoparticle-based microcarriers for targeted delivery of P/P drugs via oral, pulmonary and Blood Brain Barrier (BBB) crossing administration routes. 

• Toxicological screening of the nanocarriers and investigation of the release profile of P/P drug under various environmental conditions and the assessment of the biocompatibility and biodegradability of the new formulations. 

• Novel pulmonary P/P carriers with improved delivery features to overcome the administration difficulties and increase efficiency of protein delivery to the deep lung. 

• Oral nanoparticulate P/P carrier systems capable of adhering to the gastrointestinal mucosa and also displaying protective and permeation enhancing properties. 

• Establishment of an in vitro model for the assessment of nanocarriers permeability through the Blood Brain Barrier (BBB).

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