161 | Anle 138b inclusion complex with methyl-β-cylodextrin: a novel liquid formulation for administration in Parkinson disease

Giuditta Colangelo¹, Adriana Trapani², Giuseppe Fracchiolla², Rosa Angela Cardone³, Anna Patrizia De Nichilo², Stefano Castellani⁴, Michele Maffia⁵, Massimo Conese¹, Rosanna Mallamaci³ | ¹Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy; ²Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Bari, Italy; ³Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, Bari, Italy; ⁴Department of Precision and Regenerative Medicine and Ionian Area DiMePRe-J, University of Bari “Aldo Moro”, Bari, Italy; ⁵Department of Biological and Environmental Science and Technologies DiSTeBA, University of Salento, Lecce, Italy.

Parkinson’s disease (PD) is a widespread neurodegenerative disorder affecting millions of people worldwide, primarily characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although the exact pathogenic mechanisms remain unclear, alterations concerning the protein α-synuclein are well known to be crucial. Anle 138b, a novel drug for geriatric application in Parkinson disease (PD), suffers with/from low water solubility and low bioavailability (1,2). The current study aims at the evaluation of a formulation consisting of an inclusion complex (CX) administering Anle 138b with methyl-β-cyclodextrin (Me-β-CD). Multiple methodologies were carried out to ascertain the complex formation such as UV spectroscopy and X-ray diffraction. Furthermore, for cytocompatibility assessment, olfactory ensheathing cells (OECs) cells were treated with the CX at different doses and times of exposure. Thanks to the inclusion process we observed that Anle 138b aqueous solubility increased up to 300 times. On the other hand, the physical mixture between Anle 138b and Me-β-CD only increased drug solubility up to 70 times. All the solid-state methods adopted for CX characterization led to the conclusion that the complex is an amorphous system rather than a crystalline one. Moreover, as a model of neuronal cells, OECs cells were exposed at the CX at 6 h and 24 h, providing a reduction in cell viability when the concentration of the drug was bigger than 50 mM. The CX Anle 138b/Me-β-CD showed interesting in vitro properties, disclosing new perspectives for the development of a formulation for nose-to brain-delivery in PD treatment.

Giuditta Colangelo would like to acknowledge Gattefossè SAS (San Priest, France) for receiving a PhD Scholarship to support her future work.