Long-lasting rescue of schizophrenia-relevant cognitive impairments via risperidone-loaded microPlates.
Drug delivery
Long-acting formulations
Microparticles
Risperidone
Schizophrenia
Journal
Drug delivery and translational research
ISSN: 2190-3948
Titre abrégé: Drug Deliv Transl Res
Pays: United States
ID NLM: 101540061
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
accepted:
24
11
2021
pubmed:
2
1
2022
medline:
2
7
2022
entrez:
1
1
2022
Statut:
ppublish
Résumé
Schizophrenia is a disorder characterized by cognitive impairment and psychotic symptoms that fluctuate over time and can only be mitigated with the chronic administration of antipsychotics. Here, we propose biodegradable microPlates made of PLGA for the sustained release of risperidone over several weeks. Two microPlate configurations - short: 20 × 20 × 10 μm; tall: 20 × 20 × 20 μm - are engineered and compared to conventional ~ 10 μm PLGA microspheres in terms of risperidone loading and release. Tall microPlates realize the slowest release documenting a 35% risperidone delivery at 100 days with a residual rate of 30 ng/ml. Short microPlates and microspheres present similar release profiles with over 50% of the loaded risperidone delivered within the first 40 days. Then, the therapeutic efficacy of one single intraperitoneal injection of risperidone microPlates is compared to the daily administration of free risperidone in heterozygous knockout mice for dysbindin-1, a clinically relevant mouse model of cognitive and psychiatric liability. In temporal order object recognition tasks, mice treated with risperidone microPlates outperform those receiving free risperidone up to 2, 4, 8, and 12 weeks of observation. This suggests that the sustained release of antipsychotics from one-time microPlate deposition can rescue cognitive impairment in dysbindin mice for up to several weeks. Overall, these results demonstrate that risperidone-loaded microPlates are a promising platform for improving cognitive symptoms associated to schizophrenia. Moreover, the long-term efficacy with one single administration could be of clinical relevance in terms of patient's compliance and adherence to the treatment regimen. Single injection of long-acting risperidone-loaded µPL ameliorates the dysbindin-induced deficit in a clinically relevant mouse model of cognitive and psychiatric liability for up to 12 weeks.
Identifiants
pubmed: 34973133
doi: 10.1007/s13346-021-01099-x
pii: 10.1007/s13346-021-01099-x
pmc: PMC9242964
doi:
Substances chimiques
Antipsychotic Agents
0
Delayed-Action Preparations
0
Dysbindin
0
Risperidone
L6UH7ZF8HC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1829-1842Informations de copyright
© 2021. The Author(s).
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