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oai:docta.ucm.es:20.500.14352/924352025-03-18T15:17:24Zcom_20.500.14352_14col_20.500.14352_15

Micro- and Nano-Systems Developed for Tolcapone in Parkinson’s Disease Casanova, Yaquelyn Negro Álvarez, María Sofía Elisa Slowing Barillas, Karla Verónica García García, Luis Fernández Carballido, Ana María Rahmani, Mahdieh Barcia Hernández, Emilia María To date there is no cure for Parkinson’s disease (PD), a devastating neurodegenerative disorder with levodopa being the cornerstone of its treatment. In early PD, levodopa provides a smooth clinical response, but after long-term therapy many patients develop motor complications. Tolcapone (TC) is an effective adjunct in the treatment of PD but has a short elimination half-life. In our work, two new controlled delivery systems of TC consisting of biodegradable PLGA 502 (poly (D,L-lactide-co-glycolide acid) microparticles (MPs) and nanoparticles (NPs) were developed and characterized. Formulations MP-TC4 and NP-TC3 were selected for animal testing. Formulation MP-TC4, prepared with 120 mg TC and 400 mg PLGA 502, exhibited a mean encapsulation efficiency (EE) of 85.13%, and zero-order in vitro release of TC for 30 days, with around 95% of the drug released at this time. Formulation NP-TC3, prepared with 10 mg of TC and 50 mg of PLGA 502, exhibited mean EE of 56.69%, particle size of 182 nm, and controlled the release of TC for 8 days. Daily i.p. (intraperitoneal) doses of rotenone (RT, 2 mg/kg) were given to Wistar rats to induce neurodegeneration. Once established, animals received TC in saline (3 mg/kg/day) or encapsulated within formulations MP-TC4 (amount of MPs equivalent to 3 mg/kg/day TC every 14 days) and NP-TC3 (amount of NPs equivalent to 3 mg/kg/day TC every 3 days). Brain analyses of Nissl-staining, GFAP (glial fibrillary acidic protein), and TH (tyrosine hydroxylase) immunohistochemistry as well as behavioral testing (catalepsy, akinesia, swim test) showed that the best formulation was NP-TC3, which was able to revert PD-like symptoms of neurodegeneration in the animal model assayed 2024-01-11T09:22:31Z 2024-01-11T09:22:31Z 2022-05-17 journal article Casanova, Y.; Negro, S.; Slowing, K.; García-García, L.; Fernández-Carballido, A.; Rahmani, M.; Barcia, E. Micro- and Nano-Systems Developed for Tolcapone in Parkinson’s Disease. Pharmaceutics 2022, 14, 1080. https://doi.org/10.3390/pharmaceutics14051080 1999-4923 10.3390/pharmaceutics14051080 https://hdl.handle.net/20.500.14352/92435 https://doi.org/10.3390/pharmaceutics14051080 eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International MDPI