Steve R. Little, PhD

Chair

Professor and

Bicentennial Alumni Faculty Fellow

940 Benedum Hall | 3700 O’Hara Street | Pittsburgh, PA 15261 P: 412-624-9630 F: 412-624-9639

che@engr.pitt.edu www.che.pitt.edu

Research Focus Areas in the Little Lab

Researchers in Dr. Little’s Lab focus upon therapies that are biomimetic in that they replicate the biological function and interactions of living entities using synthetic systems. The areas of study include bioengineering, chemistry, chemical engineering, ophthalmology, and immunology. The health issues addressed include autoimmune disease, battlefield wounds, cancer, HIV, ocular diseases, and transplantation. Some of the ongoing research projects in the lab include: Mimicking Biological Structure and Behavior Using Polymeric Release Systems and Carbon Nanotubes, Treatments for Periodontitis that Restore Immunological Homeostasis, Sequential Delivery of Growth Factors for Regeneration of Tissues, and Thermo-gelling Eye Drops for the Delivery of Ophthalmic Therapies. The majority of the projects in the Little Lab utilize some aspect of controlled release for drugs, proteins, or other molecules. While such techniques are not uncommon in the field of drug delivery, our lab is unique in its ability to design such systems in silico, thereby avoiding unnecessary expenditure of time and resources on heuristic testing of controlled release formulations. Our expertise in fabricating and characterizing such systems in vitro and in vivo is augmented by our modeling capabilities.

Rational Design of Controlled Release Systems

At the University of Pittsburgh, our laboratory has developed a unique technology that allows for the specific dosing and delivery needs of a particular therapy (e.g. therapeutic concentrations of chemokine over one month or longer) to be used as “input” to generate a unique and customized formulation “recipe”. This model-aided methodology can dramatically reduce (or even completely eliminate) the need for traditional trial and error based optimization of controlled release behavior. Importantly, this can be accomplished using well-established, biodegradable polymers that are biocompatible, biodegradable and have an extraordinary track record of safety and translatability with the United States Food and Drug Administration. This unique methodology is also not only is capable of saving months to years in development time, but also able to uniquely predict a final formulation’s sensitivity to future changes in critical processing parameters, allowing designs to be optimized for consistent performance through scale-up for preclinical and clinical studies. Through projects funded on a number of NIH, NSF, DoD, State, and Private Institute-funded grants, we have developed not only the tools needed to experimentally design, build, and validate a wide variety of controlled release vehicles but also the expertise needed to troubleshoot common road-blocks in this formulation development process.

Figure 1: The Little Lab often uses the biocompatible, biodegradable polymer poly (lactic-co-glycolic acid) (PLGA) to form controlled release microspheres (A). For aqueous drugs, proteins, and peptides, the polymer matrix contains a microemulsion of e ntrapped drug (B) that is controllably released as the microsphere degrades.