Insulin, a metabolic hormone involved in glucose metabolism, plays also a neuroprotective role in the central nervous system beingable to revert the cytotoxic processes induced by Aβ42,a peptide involved in Alzheimer's disease. To reach the brain insulin have toacross the BBB therefore an additional delivery strategy results to be necessary. For these aim we performed an insulin conjugatednanogels (NGs-In). Nanogels (NGs) have a great potential in the development of “smart” nanocarriers for (bio)molecular drugs andcontrast agent for bioimaging. They are formed by physically or chemically crosslinked polymer networks, characterized by a largeand flexible surface available for multivalent bioconjugations. NGs can be produced with high yields and through-puts by pulsedelectron-beam irradiation of dilute aqueous solutions of water-soluble biocompatible polymers. In this work, a carboxylfunctionalized nanogel system (NG), generated by pulsed e-beam irradiation of a semi-dilute poly(N-vinyl pyrrolidone) (PVP)aqueous solution in the presence of acrylic acid, with an average diameter in the 60-70 nm range (PDI<0.3) was used as a substrateto generate chemically stable insulin-grafted PVP NGs. In particular, grafting was carried out using human insulin without (PVP-ginsulin)or with fluorescein isothiocyanate labeling (PVP-g-insulin-FITC). The hydrodynamic dimensions of NGs before and aftergrafting (“naked NGs” and “grafted NGs”) were investigated by Dynamic Light Scattering. For the biological application, as first step,we have evaluated the biocompatibility and immunogenicity of NGs, at different concentration, on neuroblastoma LAN5 cells andPBMCs. Moreover we have demonstrated the capacity of NGs to protect the insulin from protease action by a resistance proteinaseassay. Finally, the biological effect and neuroprotection of NGs-In has been verified.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2015|