Synthesis and characterization of different sodium hyaluronate nanoparticles to transport large neurotherapheutic molecules through blood brain barrier after stroke

Some biological drugs with proven neuroprotective capacity are unable to cross the blood brain barrier (BBB), preventing its use in neuroregenerative diseases such as stroke. The use of nanoparticles as a delivery system to transport large therapeutic molecules to the cerebral parenchyma may be a good option to overcome this limitation. To achieve this goal, we have designed some polymer nanoparticles (NPs) by two ionic gelation methods of synthesis: external (M1) and internal (M2), both using sodium hyaluronate (SH) as polymer but with differences in the elaboration of their core. Additionally, both SH-NPs were coated with chitosan and glycerol tripalmitin in order to improve their penetration capabilities into cells. The nanoparticles were characterized by size, shape and charge. Then, an experimental approach was carried out in animals submitted to a stroke model, where NPs penetration into the brain was studied and analysed after its systemic administration. All types of NPs assayed were able to cross the BBB and were endocytosed by neurons; however, the SH-NPs obtained by M2 are lightly more efficient in the rate of penetration than those obtained by M1. There were not visible differences between coated and non-coated NPs obtained by both gelation methods. This may be due to the fact that not only the size, shape and charge of NPs, but also its chemical structure influences its cellular capture by endocytic mechanisms.