Levosulpiride-loaded nanostructured lipid carriers for brain delivery with antipsychotic and antidepressant effects
- Title
- Levosulpiride-loaded nanostructured lipid carriers for brain delivery with antipsychotic and antidepressant effects
- Author
- 최한곤
- Keywords
- Levosulpiride; Nanostructured lipid carriers; Brain targeting; LPS-induced psychosis and depression mice; model; Pharmacokinetics
- Issue Date
- 2022-12
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Citation
- LIFE SCIENCES, v. 311, article no. 121198,
- Abstract
- Aims: Herein, we investigate the potential of levosulpiride-loaded nanostructured lipid carriers (LEVO-NLCs) for effective brain delivery with anti-psychotic and antidepressant effects. Main methods: Micro-emulsion method was used to prepare LEVO-NLCs, followed by its optimization using Design Expert (R), investigation of the particles properties and entrapment efficiency (%EE). Moreover, in-vitro release, in-vivo plasma and brain kinetic studies of LEVO-NLCs were executed. Anti-psychotic activity of LEVO-NLCs was accomplished in LPS-induced psychosis mice model. Additionally, expressions of neuro inflammatory mediators, neurodegeneration and neuro-inflammation in brain tissues was investigated. Key findings: The optimized LEVO-NLCs were rounded shaped nanoparticles (157.2 nm) with suitable zeta potential (-29.6 mV), low PDI (0.395) and high EE (83.67 %). No chemical interactions were found, however, the crystalline drug was changed to amorphous. LEVO-NLCs displayed sustained drug release behavior when compared with drug suspension. Moreover, a meaningfully higher AUC (106,642.27 +/- 876.44 ng.h/mL) and Cmax (38,534.72 +/- 2344.10 ng/mL) of the LEVO-NLCs in brain was observed as compared to the AUC (15,684.33 +/- 1005.49 ng.h/mL) and Cmax (7717.56 +/- 871.23 ng/mL) of LEVO-Suspension. Similar profiles of both the formulations were perceived in plasma pharmacokinetic studies. Furthermore, LEVO-NLCs exhibited a meaningfully improved anti-psychotic activity in LPS-induced psychosis mice model with reduced immobility time and enhanced struggling time. Likewise, treatment with LEVO-NLCs showed reduced levels of neuro inflammatory markers (p-NF-kappa B and COX-2) in LPS-induced mice. Additionally, no neuro-degeneration and neuroinflammation in brain tissues treated with LEVO-NLCs mice group was detected. Significance: These results concluded that NLCs may effectively be used for the brain delivery of various active pharmaceutical agents with enhanced biopharmaceutical performance.
- URI
- https://www.sciencedirect.com/science/article/pii/S0024320522008980?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/182300
- ISSN
- 0024-3205;1879-0631
- DOI
- 10.1016/j.lfs.2022.121198
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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