The research effort in the Laboratory of Biomaterials and Advanced Nano-Delivery Systems (BANDS) is focused on the development of biocompatible materials from natural and synthetic polymers, target-specific drug and gene delivery systems for cancer, CNS, inflammatory, and infectious diseases, and nanotechnology applications in medical diagnosis, imaging, and therapy.
Specific projects that we are currently pursuing include:
1) Synthesis of Novel Polymeric Biomaterials and Nanosystems
Our group has a history of developing novel polymeric materials with biocompatible surface properties. We have designed chitosan-based biomaterials with poly(ethylene glycol) and heparin surface modification using a novel non-covalent complexation-interpenetration method.
Recently, we are designing novel multifunctional polymeric nanosystems based on combinatorial-designed formulations that incorporate various functional blocks. Using hydrophilic biocompatible and biodegradable linear polymers as starting materials, we are synthesizing novel constructs for encapsulation of diverse payloads including small molecule hydrophilic and hydrophobic drugs, small interfering RNA, peptides, and genes.
2) Strategies for Overcoming Tumor Drug Resistance
An area of significant interest in the laboratory is on understanding the biology of tumor microenvironment and its role in development of drug resistance. Our hypothesis on resistant cellular phenotype is based on the role of hypoxia and accompanying aerobic glycolysis that contribute to harsh microenvironment (e.g., low pH, lack of oxygen and nutriets, etc). We postulate that cells adapting to this harsh microenvironment are becoming more resistant to apoptosis and other cell-death processes.
Our strategy to overcome resistance is based on: (1) enhancing drug delivery efficiency using nanoparticle systems that can preferentially localize in the tumor, (2) overcoming cellular resistance by lowering tumor apoptotic threshold and silencing genes that contribute to resistant phenotype, and (3) affecting the role of tumor metabolism and especially aerobic glycolysis in resistance.
3) Novel Delivery Systems for Anti-Inflammatory Therapies
Macrophages are important cells of the immune system that regulate acute and chronic inflammatory processes in the body through secretion of various cytokines and growth factors. Our approach to affect inflammatory diseases is by developing biological therapy strategies, using genes and siRNA, to down-regulate pro-inflammatory cytokines and chemokines produced by macrophages. Using macrophage-targeted nanoparticle-based delivery technologies, we are able to transfect with plasmid DNA producing anti-inflammatory therapeutics, such as IL-10 and down-regulate TNF using a targeted specific siRNA.
4) Therapeutic Strategies for CNS Diseases
The blood-brain barrier (BBB) is known to restrict transport of almost 98% of all therapeutics developed for CNS diseases. Our strategies to overcome the BBB relies on use of oil-in-water nanoemulsions developed specifically with oils rich in omega-3 polyunsaturated fatty acids (PUFA). We have found that omega-3 rich oils enhance permeability of encapsulated hydrophobic therapeutics through the BBB upon systemic and oral administration.
For hydrophilic molecules, such as peptides, proteins, siRNA, and genes, we have examined the intranasal route of administration to deliver these compounds into the brain.
5) Novel Multi-Compartmental Systems for Vaccine Delivery
Cancer vaccine are an important arsenal in the fight against this deadly disease. Our laboratory is focused on developing cancer vaccines using a multi-compartmental delivery strategy that can encapsulate different types of payloads and efficiently target antigen presenting cells upon systemic administration. As an example, we are utilized water-in-oil-in-water (W/O/W) multiple emulsion system made with squalane oil for delivery of peptide antigen gp-100 in prophylactic and therapeutic model of melanoma.
6) Delivery Systems for Anti-Infective Agents
Many antibacterials and antivirals require intracellular delivery upon systemic administration to affect reservoirs where microorganisms tend to hide from the affect of chemotherapy. Using nanoparticulate formulations that penetrate the anatomical and cellular reservoir sites, we have shown enhanced delivery efficiency and efficacy of potent antimicrobial and antiviral agents.
7) Multimodal Diagnostics and Imaging Systems
In collaboration with other scientists from academia and industry, we are developing novel constructs that incorporate optical and scattering-based targeted image contrast agents for early disease detection (e.g., oral precancer lesions) and imaging (e.g., endoscopy guided OCT imaging in colon cancer).