Targeted delivery of therapeutic and imaging agents is a highly challenging, exponentially developing area of experimental and translational biomedicine. The goal is to achieve optimal amplitude and duration of specific and safe activities of these agents in desired sites - target cells, or tissues. This limits collateral damage inflicted by drugs, for example, by toxic anticancer agents or anti-thrombotic agents predisposing to bleeding. Precise delivery into specific cellular compartments is needed for action of many tentatively potent biological therapeutics including enzymes and genes. Targeted drug delivery will improve treatment of pathological conditions including cancer, cardiovascular, metabolic and genetic diseases, diabetes, inflammation and infectious diseases, among many others.
Recombinant fusion proteins, liposomes, polymer nanocarriers, monoclonal antibodies and other affinity ligands provide modular elements for design of multi-functional drug delivery systems. Issues including biocompatibility of these systems and adverse side effects inflicted by targeting are central to their safety and clinical utility. Stealth technologies involving coating injectable objects with masking molecules optimize their circulation and minimize side effects. Carriers with controlled rates of degradation and drug release afford prolonged and smooth kinetics of therapeutic effects.
Research in targeted drug delivery is actively pursued in many laboratories at the University of Pennsylvania in the Schools of Medicine, Engineering and CHOP. Research activities of these groups include design of the biomaterials and carriers for drug delivery, identification of molecular targets for cell-specific delivery, studies of targeting, binding, sub-cellular trafficking and metabolism of the targeted drugs. These studies use modern strategies of nanotechnology, bioconjugation and recombinant fusion proteins, phage display libraries, cellular grafting, monoclonal antibodies, bioengineering and computational modeling, diverse imaging modalities and pharmacokinetic studies in animals. Testing of therapeutic and side effects of drug targeting is pursued in diverse experimental models including cell cultures and pre-clinical animal studies.
Currently, research activities of the Core labs of the Program in Targeted Therapeutics (PTT, 823 BRB II/III) are focused on developing new strategies for vascular drug delivery for treatment of acute and sub-acute pathological conditions including cardiovascular, oncological and metabolic diseases. The PTT mission also includes facilitation of coordinated research efforts in this area at PENN and other participating institutions (Drexel University, PA Nanotechnology Institute) and developing graduate teaching at PENN in the area of drug delivery and targeting.