Benchmarking Bicontinuous Nanospheres against Polymersomes for in Vivo Biodistribution and Dual Intracellular Delivery of Lipophilic and Water-Soluble Payloads

Bicontinuous nanospheres (BCNs) are polymeric analogs to lipid cubosomes, possessing cubic liquid crystalline phases with high internal surface area, aqueous channels for loading hydrophilic molecules, and high hydrophobic volume for lipophilic payloads. Primarily due to difficulties in scalable and consistent fabrication, neither controlled delivery of payloads via BCNs nor their organ or cellular biodistributions following in vivo administration have been demonstrated or characterized. We have recently validated flash nanoprecipitation as a rapid method of assembling uniform monodisperse 200–300 nm diameter BCNs from poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-b-PPS) co-polymers. Here, we compare these BCNs both in vitro and in vivo to 100 nm PEG-b-PPS polymersomes (PSs), which have been well characterized as nanocarriers for controlled delivery applications. Using a small molecule fluorophore and a fluorescently tagged protein as respective lipophilic and water-soluble model cargos, we demonst...