Sustained release of RNA nanoparticles from reservoir implant for ocular delivery

Previous studies of RNA nanoparticles have demonstrated the potential of these nanoparticles in ocular delivery via the subconjunctival route. Sustained ocular delivery is beneficial for chronic eye disease treatment, and utilizing a reservoir implant in the periocular space (e.g., episcleral implant) can prolong ocular delivery of these nanoparticles. The objectives of the present study were to (a) demonstrate the fabrication of the reservoir implants, (b) evaluate the performance of the implants with model permeants and RNA nanoparticles in vitro, and (c) investigate the applicability of hindered transport theory for the release kinetics from the implants. In vitro release testing was performed with the implants to determine the release kinetics and implant membrane permeability. In addition to RNA nanoparticles, model permeants fluorescein-isothiocyanate (FITC) labeled dextrans (10, 40, and 150 kDa) were examined. The results indicated that the rates of permeant release from the implants were a function of the (a) size and structure of the permeant/nanoparticle and (b) type and pore size of the implant membrane. The model analyses provided insights into implant membrane transport and ocular pharmacokinetics of the nanoparticles for transscleral delivery. The results suggested the potential of prolonged delivery of the RNA nanoparticles with the episcleral implant approach.