Biography
Biography: Whitney Shatz
Abstract
Statement of the Problem: Age-related macular degeneration is an eye disease affecting the back of the eye which gradually destroys sharp central vision [1], and has the potential to greatly impact quality of life [2]. Intravitreal injection is the preferred route for ocular drug delivery of protein therapeutics, where maximal benefit is achieved with dosing every 4-8 weeks [3]. Less frequent dosing would reduce treatment burden and increase patient compliance [4], highlighting the need for long-acting delivery (LAD) technologies. Methodology and Theoretical Orientation: Since clearance from the eye is governed primarily by diffusion [5], therapeutic Fab was chemically conjugated to various multivalent scaffolds via maleimide chemistry to increase Fab half-life. Each Fab-conjugate candidate was assessed based on a multitude of criterial including conjugation efficiency, ratio of Fab to carrier, hydrodynamic radius, long terms stability, viscosity and activity (Figure 1). In some cases, in vivo tolerability experiments were performed to assess biocompatibility with ocular tissues. Findings: Evaluation of each system revealed attributes desirable for ocular LAD. Scaffolds composed of either PEG, HPMA or lipoprotein were effective in increasing Fab RH. Geometry did not greatly influence RH but had an impact on viscosity. Biocompatibility study demonstrated tolerability of PEG but not of lipoprotein carrier. Conclusion and Significance: Though RH measurements in vitro are useful for predicting vitreal half-life [6], scaffold biocompatibility is more complicated and has remained a major hurdle to the success of novel technologies.