Formulation and optimization of xanthohumol loaded solid dispersion for effective treatment of Parkinson's disease in rats: In vitro and in vivo assessment

Xanthohumol (XH) is a prenylated flavonoid that possesses neuroprotective effects by increasing the levels of dopamine (DA), reducing oxidative stress, and neuroinflammation against Parkinson's disease (PD). However, the neuroprotective efficacy of XH in managing PD is limited by its low solubi...

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Published in:Journal of drug delivery science and technology 2024-12, Vol.102, p.106385, Article 106385
Main Authors: Alam, Md Shahbaz, Khandale, Nikhil, Birla, Devendra, Bashir, Bushra, Vishwas, Sukriti, Kulkarni, Mangesh P., Rajput, Rakesh Prakash, Pandey, Narendra Kumar, Loebenberg, Raimar, Davies, Neal M., Gupta, Gaurav, Dureja, Harish, Kumbhar, Popat, Disouza, John, Kumar, Puneet, Dua, Kamal, Singh, Sachin Kumar
Format: Article
Language:English
Subjects:
Neurodegeneration
Parkinson's disease
Quality by design
Solid dispersion
Xanthohumol
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Summary:Xanthohumol (XH) is a prenylated flavonoid that possesses neuroprotective effects by increasing the levels of dopamine (DA), reducing oxidative stress, and neuroinflammation against Parkinson's disease (PD). However, the neuroprotective efficacy of XH in managing PD is limited by its low solubility, poor bioavailability, and less blood-brain barrier (BBB) permeability leading to decreased therapeutic activity. To overcome these limitations, XH-loaded solid dispersion (SD) has been formulated using the Central Composite Design (CCD) approach. The optimized formulation was evaluated by determining the angle of repose, drug loading, percentage drug release, PXRD, DSC, FTIR, and SEM. The results of PXRD, DSC, and SEM demonstrated the formation of SD. The XH-SD showed a 6.45-fold enhancement in dissolution rate, a 12.7-fold increase in Cmax, and 26.11-fold increase in XH's area under curve (AUC) as compared to the naïve XH. In the pharmacokinetic studies, XH-SD showed a 42.20 folds increase in relative bioavailability(0-∞) compared to naïve XH. To assess pharmacodynamic effects, PD was induced using rotenone. The motor and non-motor functions were evaluated by assessing various behavioral parameters such as catalepsy, spontaneous locomotor activity and muscle coordination test. The formulation exhibited dose-dependent effects, with both low and high doses of XH-SD resulting in significant enhancements (P 
ISSN:1773-2247
DOI:10.1016/j.jddst.2024.106385