mPEG-PLGA Nanoparticles Labelled with Loaded or Conjugated Rhodamine-B for Potential Nose-to-Brain Delivery

Nowdays, neurodegenerative diseases represent a great challenge from both the
therapeutic and diagnostic points of view. Indeed, several physiological barriers of the body,
including the blood brain barrier (BBB), nasal, dermal, and intestinal barriers, interpose between
the development of new drugs and their effective administration to reach the target organ or target
cells at therapeutic concentrations. Currently, the nose-to-brain delivery with nanoformulations
specifically designed for intranasal administration is a strategy widely investigated with the goal to
reach the brain while bypassing the BBB. To produce nanosystems suitable to study both in vitro
and/or in vivo cells trafficking for potential nose-to-brain delivery route, we prepared and
characterized two types of fluorescent poly(ethylene glycol)-methyl-ether-block-poly(lactide-coglycolide)
(PLGA-PEG) nanoparticles (PNPs), i.e., Rhodamine B (RhB) dye loaded- and grafted-
PNPs, respectively. The latter were produced by blending into the PLGA-PEG matrix a RhB-labeled
polyaspartamide/polylactide graft copolymer to ensure a stable fluorescence during the time of
analysis. Photon correlation spectroscopy (PCS), UV-visible (UV-vis) spectroscopies, differential
scanning calorimetry (DSC), atomic force microscopy (AFM) were used to characterize the RhBloaded
and RhB-grafted PNPs. To assess their potential use for brain targeting, cytotoxicity tests
were carried out on olfactory ensheathing cells (OECs) and neuron-like differentiated PC12 cells.
Both PNP types showed mean sizes suitable for nose-to-brain delivery (<200 nm, PDI < 0.3) and were not cytotoxic toward OECs in the concentration range tested, while a reduction in the viability on PC12 cells was found when higher concentrations of nanomedicines were used. Both the RhBlabelled NPs are suitable drug carrier models for exploring cellular trafficking in nose-to-brain delivery for short-time or long-term studies.