Highly stabilized nanocrystals delivering Ginkgolide B in protecting against the Parkinson’s disease

et al. 2022

Nano-Micro Lett.

Self Cite

Parkinson’s disease (PD), a neurodegenerative disease that shows a high incidence in older individuals, is becoming increasingly prevalent. Unfortunately, there is no clinical cure for PD, and novel anti-PD drugs are therefore urgently required. However, the selective permeability of the blood–brain barrier (BBB) poses a huge challenge in the development of such drugs. Fortunately, through strategies based on the physiological characteristics of the BBB and other modifications, including enhancement of BBB permeability, nanotechnology can offer a solution to this problem and facilitate drug delivery across the BBB. Although nanomaterials are often used as carriers for PD treatment, their biological activity is ignored. Several studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio effects. In this review, we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD treatment. Subsequently, we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological effects. Finally, we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this field. Our review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.

Section: Applications Of Bbb-crossing Strategies For Pd Treatmentmentioning

confidence: 99%

Anti-Parkinsonian Therapy: Strategies for Crossing the Blood–Brain Barrier and Nano-Biological Effects of Nanomaterials

Cheng

et al. 2022

Nano-Micro Lett.

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“…23,24 Mice in the GB and GB-NP treatment groups were gavaged with either GB (5 mg/kg) together with blank NPs or GB-NPs (5 mg/kg) for 14 days (once daily for 7 days prior to MPTP administration and twice daily for 7 days after MPTP administration). 25 Control mice were administered only 0.9% saline, while animals in the Selegiline group were administered Selegiline (10 mg/kg). GB-NPs-mediated neuroprotection was quantified based on behavioral testing, TH + neuron immunohistochemistry, and by measuring levels of DA and metabolites.…”

Section: Dovepressmentioning

confidence: 99%

“…We next sought to explore the in vivo toxicity of GB-NPs by using them to treat zebrafish embryos at 6 hpf across a range of concentrations (25,50, and 100 μg/ mL). We then monitored these embryos for any abnormalities in development, blood flow, or other changes at 24, 48, 72, and 96 hpf.…”

Section: Vivo Gb-nps Toxicity Evaluationmentioning

confidence: 99%

“…Notably, following oral administration, GB-NPs has longer T max and MRT 0-t and higher AUC 0-t compared with the GB nanocrystals. 25 We also quantified the cerebral GB concentrationtime profile and associated pharmacokinetic parameters ( Figure 5B and Table 1, respectively) after GB-NPs oral administration. We found that GB-NPs required a longer time (6.84 ± 0.63h) to reach T max relative to free GB (4.73 ± 0.51 h), but that GB-NPs were associated with a significantly higher C max than was free GB (0.17 ± 0.01 μg/g vs 0.09 ± 0.01 μg/g).…”

Section: Analysis Of Gb-nps Pharmacokineticsmentioning

confidence: 99%

See 1 more Smart Citation

Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease

Zhao

Xiong

et al. 2020

IJN

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Purpose Ginkgolide B (GB) is a terpene lactone derivative of Ginkgo biloba that is believed to function in a neuroprotective manner ideal for treating Parkinson’s disease (PD). Despite its promising therapeutic properties, GB has poor bioavailability following oral administration and cannot readily achieve sufficient exposure in treated patients, limiting its clinical application for the treatment of PD. In an effort to improve its efficacy, we utilized poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) nanoparticles as a means of encapsulating GB (GB-NPs). These NPs facilitated the sustained release of GB into the blood, thereby improving its ability to accumulate in the brain and to treat PD. Methods and Results Using Madin-Darby canine kidney (MDCK) cells, we were able to confirm that these NPs could be taken into cells via multiple nonspecific mechanisms including micropinocytosis, clathrin-dependent endocytosis, and lipid raft/caveolae-mediated endocytosis. Once internalized, these NPs tended to accumulate in the endoplasmic reticulum and lysosomes. In zebrafish, we determined that these NPs were readily able to undergo transport across the chorion, gastrointestinal, blood–brain, and blood-retinal barriers. In a 1-methyl-4-phenylpyridinium ion (MPP + )-induced neuronal damage model system, we confirmed the neuroprotective potential of these NPs. Following oral administration to rats, GB-NPs exhibited more desirable pharmacokinetics than did free GB, achieving higher GB concentrations in both the brain and the blood. Using a murine PD model, we demonstrated that these GB-NPs achieved superior therapeutic efficacy and reduced toxicity relative to free GB. Conclusion In conclusion, these results indicate that NPs encapsulation of GB can significantly improve its oral bioavailability, cerebral accumulation, and bioactivity via mediating its sustained release in vivo.

“…The roles of ginkgolides in IIR are also supported by the study of Kim et al, wherein they found that GB can significantly attenuate the increase of the NF-κB DNA-binding activity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (can induce PD rodent model through an NF-κB-dependent mechanism; Kim et al, 2013 ). Furthermore, PD model treatment with GB-nanocrystals (GB-NCs) can improve behavior, reduce dopamine deficiency, and elevate dopamine metabolite levels (Liu et al, 2020 ). Thus, BB and GB provide a therapeutic approach to rescue the PD by regulating IIR.…”

Section: Roles Of Ginkgolides In the Inflammatory Immune Response Of mentioning

confidence: 99%

Role of Ginkgolides in the Inflammatory Immune Response of Neurological Diseases: A Review of Current Literatures

et al. 2020

Front. Syst. Neurosci.

The inflammatory immune response (IIR) is a physiological or excessive systemic response, induced by inflammatory immune cells according to changes in the internal and external environments. An excessive IIR is the pathological basis for the generation and development of neurological diseases. Ginkgolides are one of the important medicinal ingredients in Ginkgo biloba. Many studies have verified that ginkgolides have anti-platelet-activating, anti-apoptotic, anti-oxidative, neurotrophic, and neuroimmunomodulatory effects. Inflammatory immunomodulation is mediated by inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. They also inhibit the platelet-activating factor (PAF)mediated signal transduction to attenuate the inflammatory response. Herein, we reviewed the studies on the roles of ginkgolides in inflammatory immunomodulation and suggested its potential role in novel treatments for neurological diseases.