Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats

Yang, Xinxin; Zheng, Ruiyuan; Cai, Yunpeng; Liao, Mai; Yuan, Weien; Liu, Zhenguo

doi:10.2147/ijn.s30463

Cited by 30 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MP subcutaneously administered improved motor function and stepping of the lesioned forepaw in the 6-hydroxydopamine (6-OHDA) PD rat model. LP-be-NP were also able to significantly reduce the axial, limb, orolingual and locomotive L-DOPA-induced abnormal involuntary movements or dyskinesia in the same PD model, compared to the free drug [20]. L-DOPA-induced dyskinesia molecular markers were significantly reduced in the rats presenting involuntary movements and treated with LP-be-NP.…”

Section: Dds For Levodopa Deliverymentioning

confidence: 82%

Drug development in Parkinson's disease: From emerging molecules to innovative drug delivery systems

2013

View full text Add to dashboard Cite

Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease.Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood brain barrier and target a specific region are still needed.Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly-targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients.

show abstract

Section: Dds For Levodopa Deliverymentioning

confidence: 82%

Drug development in Parkinson's disease: From emerging molecules to innovative drug delivery systems

2013

View full text Add to dashboard Cite

show abstract

“…A recent study has indicated that intermittent levodopa treatment induced increased phosphorylation of AMPA in the striatum of PD rats 9. The current authors have previously reported that levodopa/benserazide-loaded microspheres, which release levodopa and benserazide in a sustained manner, could be used to reduce established LID in a rat model of PD 10. However, whether AMPA receptor is involved in the mechanisms by which levodopa/benserazide microspheres reduce LID in dyskinetic rats was still unknown.…”

Section: Introductionmentioning

confidence: 89%

“…Levodopa methyl ester/benserazide-loaded microspheres were prepared as reported previously 10–12. LDME-loaded microspheres were prepared according to the oil-in-water emulsion solvent evaporation method.…”

Section: Methodsmentioning

confidence: 99%

Levodopa/benserazide microspheres reduced levodopa-induced dyskinesia by downregulating phosphorylated GluR1 expression in 6-OHDA-lesioned rats

Yang¹,

Chen²,

Xiang³

et al. 2012

DDDT

Self Cite

View full text Add to dashboard Cite

BackgroundLevodopa is the gold standard in the treatment of Parkinson’s disease (PD). However, long-term levodopa replacement therapy is accompanied by abnormal involuntary movements (AIMs), known as levodopa-induced dyskinesia (LID). Until now, the precise mechanisms of LID were only partially understood. Previous studies have shown that continuous dopamine stimulation was helpful in reducing the expression of LID. In addition to dopamine D1 receptor, glutamatergic receptors such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor also contribute to the expression of LID. The current authors have previously reported that levodopa/benserazide-loaded microspheres could ameliorate the expression of LID by reducing the protein kinase A signaling pathway in dyskinetic rats. However, whether AMPA receptor is involved in the mechanism by which levodopa/benserazide-loaded microspheres ameliorate the expression of LID in dyskinetic rats was unknown.MethodsIn the present study, as reported previously, levodopa and benserazide were loaded by poly(lactic-co-glycolic acid) microspheres, which can release levodopa and benserazide in a sustained manner. 6-Hydroxydopamine was injected into the right medial forebrain bundle to produce a rat model of PD. Then valid PD rats were treated with levodopa plus benserazide for 3 weeks to induce a rat model of LID. Dyskinetic rats were treated with levodopa/beserazide-loaded microspheres containing levodopa (6 mg/kg) plus benserazide (15 mg/kg) or same dose of levodopa plus benserazide. Abnormal involuntary movements were measured in rats on days 1, 5, 10, 15, and 20 during the treatment. The levels of GluR1 at serine-831 (pGluR1S831) and serine-845 (pGluR1S845) were determined by Western blot. Arc and proenkephalin (Penk) levels were measured by real-time polymerase chain reaction.ResultsThree-week levodopa plus benserazide treatment induced dyskinesia in PD rats. Levodopa/benserazide-loaded microsphere-treated dyskinetic rats showed lower AIM scores than levodopa plus benserazide-treated dyskinetic rats. Microsphere treatment downregulated the phosphrylated levels of pGluR1S831 and pGluR1S845 in the striatum of dyskinetic rats. In addition, microsphere treatment reduced the levels of Arc and Penk.ConclusionThese data indicated that levodopa/benserazide-loaded microspheres could be used to ameliorate the expression of LID by reducing the expression of pGluR1S831 and pGluR1S845 as well as Arc and Penk.

show abstract

“…This method of administering levodopa successfully abolished levodopa-induced dyskinesia in rats. 118 More recently, intranasal delivery of levodopa NPs has been explored. 119 Levodopa encapsulated in chitosan NPs was incorporated in a thermo-reversible gel prepared using Pluronic PF127, and then delivered via intranasal route, which increased drug levels in the brain.…”

Section: Nanomedicine and Neurodegenerative Diseasesmentioning

confidence: 99%

Nanoneuromedicines for degenerative, inflammatory, and infectious nervous system diseases

Gendelman

Anantharam

Bronich

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

104

View full text Add to dashboard Cite

Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated. The need for improved health care, treatment and diagnostics are immediate. A means to such an end is nanotechnology. Indeed, recent developments of health-care enabling nanotechnologies and nanomedicines range from biomarker discovery including neuroimaging to therapeutic applications for degenerative, inflammatory and infectious disorders of the nervous system. This review focuses on the current and future potential of the field to positively affect clinical outcomes.

show abstract

Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats

Cited by 30 publications

References 27 publications

Drug development in Parkinson's disease: From emerging molecules to innovative drug delivery systems

Drug development in Parkinson's disease: From emerging molecules to innovative drug delivery systems

Levodopa/benserazide microspheres reduced levodopa-induced dyskinesia by downregulating phosphorylated GluR1 expression in 6-OHDA-lesioned rats

Nanoneuromedicines for degenerative, inflammatory, and infectious nervous system diseases

Contact Info

Product

Resources

About