PLGA-PEG-ANG-2 Nanoparticles for Blood–Brain Barrier Crossing: Proof-of-Concept Study
Gina P. Hoyos-Ceballos,
Barbara Ruozi,
Ilaria Ottonelli,
Federica Da Ros,
Maria Angela Vandelli,
Flavio Forni,
Eleonora Daini,
Antonietta Vilella,
Michele Zoli,
Giovanni Tosi,
Jason T. Duskey,
Betty L. López-Osorio
Affiliations
Gina P. Hoyos-Ceballos
Grupo de Investigación Ciencia de los Materiales, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 62 No. 52–59, Medellín 050015, Colombia
Barbara Ruozi
Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
Ilaria Ottonelli
Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
Federica Da Ros
Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
Maria Angela Vandelli
Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
Flavio Forni
Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
Eleonora Daini
Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, 41124 Modena, Italy
Antonietta Vilella
Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, 41124 Modena, Italy
Michele Zoli
Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, 41124 Modena, Italy
Giovanni Tosi
Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
Jason T. Duskey
Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
Betty L. López-Osorio
Grupo de Investigación Ciencia de los Materiales, Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Calle 62 No. 52–59, Medellín 050015, Colombia
The treatment of diseases that affect the central nervous system (CNS) represents a great research challenge due to the restriction imposed by the blood−brain barrier (BBB) to allow the passage of drugs into the brain. However, the use of modified nanomedicines engineered with different ligands that can be recognized by receptors expressed in the BBB offers a favorable alternative for this purpose. In this work, a BBB-penetrating peptide, angiopep-2 (Ang−2), was conjugated to poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles through pre- and post-formulation strategies. Then, their ability to cross the BBB was qualitatively assessed on an animal model. Proof-of-concept studies with fluorescent and confocal microscopy studies highlighted that the brain-targeted PLGA nanoparticles were able to cross the BBB and accumulated in neuronal cells, thus showing a promising brain drug delivery system.
