FIGURE 8.

Design strategies for the intravenous (IV) nanoparticle formulation (IV-NPF) and intranasal nanoparticle formulation (IN-NPF) of Ru265 and IRX4204, respectively. (A) The IV-NPF shell is comprised of DPLC and DSPE-PEG. The IV-NPF is decorated with GYR, TAT, and CLE by attaching these targeting peptides to DSPE-PEG. (B) The IV-NPF core is constructed using polymers of PLA and PLGA. ROS-sensitive linkers such as thioketal, ethyl methacrylate and phenyl boronic ester are incorporated into the PLA/PLGA polymer backbone. (C) The IN-NPF shell is also comprised of DPLC and DSPE-PEG-GYR, DSPE-PEG-TAT, and DSPE-PEG-CLE. ROS-sensitive linkers such as thioketal, ethyl methacrylate and phenyl boronic ester are incorporated into the PLA/PLGA polymer backbone. (D) The IN-NPF is also coated with low molecular weight PSACC such as dextrin, carboxymethylcellulose, and chitosan to have a long retention time at the nasal mucosal surface and high absorption by nasal epithelia thus minimizing drug exposure in the respiratory system. (See sections “7.3. Construction of NPs for systemic drug delivery to the brain: Building blocks and functional components” and “7.4. Drug delivery to the brain by intranasal administration of NPs” for abbreviations and formulation details).