Project 1: Elastin-like polypeptide stabilizes recombinant cyclophilin into a nanoparticle; Project 2: Encapsulation of Rhesus theta defensin-1 (RTD-1) in PEG-PLGA nanoparticles for aerosol delivery in CF; Project 3: A biomimetic solution to the generation of hemoglobin-based oxygen carriers

Abstract

We explore a new strategy to carry CsA that utilizes its human target, a protein called cyclophilin, to which CsA binds with a Kd of 36.8 nM. Due to its low MW (1.2 kD), cyclophilin is below the renal filtration cutoff (<40 kD) and would be rapidly filtered from the blood by the kidneys. To overcome this limitation, we used recombinant protein-engineering to increase the molecular weight of cyclophilin through recombinant fusion with a 73 kD elastin-like polypeptide (ELP). Since recent advances in drug delivery using nanoparticle technologies have indicated that appropriate drug delivery vehicles can achieve sustained release to the airways, here we are trying to encapsulate highly hydrophilic RTD-1 into PEG-PLGA-based microparticles to achieve extended retention time in the lung, which might imply better therapeutic effect against lung symptoms of CF. We proposed that fusing hemoglobin to one particle elastin-like polypeptides can help to prevent extravasation and reduce the nitric oxide scavenging-mediated toxicities. Chemical conjugation has been investigated. Highly controllable molecular cloning will also be studied.