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

Emanuela Fabiola Craparo; Teresa Musumeci; Angela Bonaccorso; Rosalia Pellitteri; Alessia Romeo; Irina Naletova; Lorena Maria Cucci; Gennara Cavallaro; Cristina Satriano

doi:10.3390/pharmaceutics13091508

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

Pharmaceutics. 2021 Sep 18;13(9):1508. doi: 10.3390/pharmaceutics13091508.

Authors

Affiliations

¹ Department of Biological, Chemical and Pharmaceutical Science and Technologies (STEBICEF), 90123 Palermo, Italy.
² Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy.
³ Institute for Biomedical Research and Innovation, National Research Council, 95126 Catania, Italy.
⁴ PhD in Neuroscience, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95125 Catania, Italy.
⁵ Inter-University Consortium for Research on the Chemistry of Metal Ions in Biological Systems, University of Bari, 70126 Bari, Italy.
⁶ Institute of Crystallography, Research National Council, 95126 Catania, Italy.
⁷ Department of Chemical Science, University of Catania, 95125 Catania, Italy.

Abstract

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-co-glycolide) (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 RhB-loaded 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 RhB-labelled NPs are suitable drug carrier models for exploring cellular trafficking in nose-to-brain delivery for short-time or long-term studies.

Keywords: PC12 cell line; co-polymers; fluorescent dye; imaging; nanomedicine; olfactory ensheathing cells.

Grants and funding

57722172124/University of Catania