CAREER: Hyperbranched Polymeric Micelles as Novel Drug Delivery Systems

Rutgers University New Brunswick, New Brunswick NJ

Investigators

Abstract

9983272 Uhrich Micelles are colloids frequently used as drug delivery systems because of several useful properties. First, the hydrophobic microenvironment of micelles can water-solubilize hydrophobic drugs, expanding the pharmaceutical potential of otherwise useful compounds. This function has long been investigated as a means of improving solubility for drug delivery, particularly for parenteral or oral administration, as well as for ophthalmic, topical, rectal and nasal delivery. A second important function of micelles is their small size (less than 100 nm) which allows them to evade the reticuloendothelial system (RES) and behave as passive targeting agents. Third, the interplay between the hydrophobic domains of the polymer carriers and hydrophobic lipids of cell membranes enables micelles to be inserted into or passed through cell membranes. Yet there is no systematic understanding of the factors that govern their ability to interact with cell membranes. Lastly, the major drawback to their extended clinical use is that micelles are thermodynamically unstable; they disorganize upon dilution in the bloodstream, by temperature increases or by interacting with various blood components. The desirable features of micelles as described above can be used to design a polymer system that models micellar systems yet overcomes their major limitation by covalently binding the "unimers" such that dilution is not possible. Our goal is to develop rationally designed polymeric materials that can be used to understand the interactions and mechanisms of cell-biomaterial interfaces. Our long-term objective is to use these polymeric micelles to probe cell-material interactions then design and develop enhanced drug delivery systems. The foundation of this proposal is our synthesis of hyperbranched polymers that can encapsulate, and subsequently release, hydrophobic molecules as well as to enhance fusion processes in liposomes. These polymeric materials are designed to biodegrade into nontoxic components over defined time period (i.e., months), thus eliminating concerns of long-term effects. With the development of the proposed polymeric systems, we have the capability to systematically study the behavior of micelles - information that was previously unattainable due to the lack of appropriates materials. Completion of this research will impact areas of drug delivery, controlled release, membrane technologies, biomaterials, and biocatalysis. The continued growth and productivity of our society is dependent upon people with the appropriate technological skills. Minorities and women, while representing a majority in American society, are currently underrepresented in the sciences. It is imperative that we train minorities and women in science and engineering to ensure the health of our economy and provide support such that these students remain in the science pipeline. Two specific programs are proposed to address these issues. First, to enhance participation of girls in science by reaching elementary school-age girls, an outreach program will be coordinated with Girl Scouts and with women in science at Rutgers University. Second, Rutgers has a strong mentoring program for undergraduate women in science, but there are no formal mentoring programs for graduate women. A program that allies graduate women with faculty mentors will be developed.