Screening of chemical linkers for development of pullulan bioconjugates for intravitreal ocular applications

The treatment of posterior segment disorders the eye requires therapeutic strategies to achieve drug effects over prolonged times. Innovative colloidal delivery systems can be designed deliver drugs retina and prolong their intravitreal permanence. In order exploit pullulan (Pull) as polymeric carrier for delivery, derivatives hydrophobic model molecule rhodamine B (RhB) were conjugated backbone through linkers with different stability, namely ether (Et), hydrazone (Hy) or ester (Es) bond obtain Pull-Et-RhB, Pull-Hy-RhB Pull-Es-RhB, respectively. Dynamic light scattering transmission electron microscopy analyses showed that polymer conjugates self-assembled into 20-25 nm particles. Pull-Et-RhB was fairly stable at all tested pH values. At vitreal 7.4, 50% RhB released from Pull-Es-RhB in 11 6 days, endosomal (5.5), 4 1 Multiple particle tracking ex vivo porcine diffusivity bioconjugates vitreous about 103 times lower than water. Flow cytometry confocal are remarkably taken up by retinal RPE cells. studies after injection mice, localize ganglion cell layer inner outer plexiform layers. particles detected also inside blood vessels. These results demonstrate tailored conjugation is a promising vehicle long-acting injectables capable permeate retina.