Preparation of Rotigotine-Loaded Microspheres and Their Combination Use with L-DOPA to Modify Dyskinesias in 6-OHDA-Lesioned Rats

Wang, Aiping; Wang, Lexi; Sun, Kaoxiang; Liu, Wanhui; Sha, Chunjie; Li, Youxin

doi:10.1007/s11095-012-0762-0

Cited by 37 publications

(16 citation statements)

References 33 publications

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“…They are thus good candidates for being formulated in DDS. With this aim, Wang et al, [22] developed rotigotine loaded PLGA MP (Ro-MP) for the continuous release of this D1/D2/D3 DA agonist.…”

Section: Dds For Agonist Deliverymentioning

confidence: 99%

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

2013

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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.

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Section: Dds For Agonist Deliverymentioning

confidence: 99%

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

2013

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“…This statement is supported by data generated from a functional miRNA screening platform that indicate that only 60% of the miRNome is functional in cells [123]. Furthermore, miRNAs are also dynamically regulated, spatially and temporally regulated in animal development [109, 124] but also during development of chronic diseases [125]. Underestimating these miRNA features might result in delivery of inappropriately dosed miRNA therapeutics in targeted tissues as well as inappropriate time point for drug administration.…”

Section: Discussionmentioning

confidence: 98%

“…This abnormality causes muscular atrophy, weakness and cognitive disturbances [107, 108]. Studies demonstrated that pharmacological drugs [109], plasmid DNA-PEI complexes [110] and viral vectors [111-113] injected intramuscularly can be transported from the muscles into the brain. Myiazaki et al .…”

Section: State Of the Art Of Current Experi- Mental Research On MImentioning

confidence: 99%

Pharmacomodulation of microRNA Expression in Neurocognitive Diseases: Obstacles and Future Opportunities

Simion¹,

Nadim²,

Bénédetti³

et al. 2017

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Given the importance of microRNAs (miRNAs) in modulating brain functions and their implications in neurocognitive disorders there are currently significant efforts devoted in the field of miRNA-based therapeutics to correct and/or to treat these brain diseases. The observation that miRNA 29a/b-1 cluster, miRNA 10b and miRNA 7, for instance, are frequently deregulated in the brains of patients with neurocognitive diseases and in animal models of Alzheimer, Huntington’s and Parkinson’s diseases, suggest that correction of miRNA expression using agonist or antagonist miRNA oligonucleotides might be a promising approach to correct or even to cure such diseases. The encouraging results from recent clinical trials allow envisioning that pharmacological approaches based on miRNAs might, in a near future, reach the requirements for successful therapeutic outcomes and will improve the healthcare of patients with brain injuries or disorders. This review will focus on the current strategies used to modulate pharmacological function of miRNA using chemically modified oligonucleotides. We will then review the recent literature on strategies to improve nucleic acid delivery across the blood-brain barrier which remains a severe obstacle to the widespread application of miRNA therapeutics to treat brain diseases. Finally, we provide a state-of-art of current preclinical research performed in animal models for the treatment of neurocognitive disorders using miRNA as therapeutic agents and discuss future developments of miRNA therapeutics.

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“…These are not without their side effects (many similar to l-DOPA treatment) and research groups are also investigating the use PLGA based microscale carriers as a means of sustained release of agonists such as apomorphine [194] or delivery of rotigotine [195,196] to the brain. Wang et al, were able to show that rotigotine loaded PLGA microspheres administered in conjunction with l-DOPA, reduced the abnormal involuntary movements (dyskinesias) associated with l-DOPA therapy compared to the control group (l-DOPA alone) in the 6-OHDA rat model of PD [195]. These preclinical studies, showing the ability of PLGA micro/nanoparticles to deliver therapeutic agents to the animal brain, could mean that a fundamental change in the way PD drugs are administered might not be too far from reality.…”

Section: Polymers As Drug Carriersmentioning

confidence: 99%

“…The combination of microsphere and pulsatile l-DOPA delivery produced no better therapeutic benefit than mono l-DOPA administration but significantly decreased dyskinesia (2012) [195] PLGA microspheres Rasagiline mesylate (RM) intraperitoneal Rotenone rat model RM administered via microspheres resulted in no additional therapeutic than RM in saline, but allowed administration every two weeks (2012) [196] PLGA microspheres Rotigotine intramuscular…”

Section: Polymeric Gene Vectorsmentioning

confidence: 99%

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

Newland

Werner

et al. 2015

Progress in Polymer Science

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a b s t r a c tParkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and represents a growing health burden to western societies. Like many neurodegenerative disorders the cause is unknown, however, as the pathogenesis becomes ever more elucidated, it is becoming clear that effective delivery is a key issue for new therapeutics. The versatility of today's polymerization techniques allows the synthesis of a wide range of polymer materials which hold great potential to aid in the delivery of small molecules, proteins, genetic material or cells. In this review, we capture the recent advances in polymer based therapeutics of the central nervous system (CNS). We place the advances in historical context and, furthermore, provide future prospects in line with newly discovered advancements in the understanding of PD and other neurodegenerative disorders. This review provides researchers in the field of polymer chemistry and materials science an up-to-date understanding of the requirements placed upon materials designed for use in the CNS aiding the focus of polymer therapeutic design.

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Preparation of Rotigotine-Loaded Microspheres and Their Combination Use with L-DOPA to Modify Dyskinesias in 6-OHDA-Lesioned Rats

Abstract: RoMS could supply an alternative of CDS for the treatment of PD and the study indicates a potential advantage of RoMS for the treatment of mild and advanced PD patient in combination with L-DOPA.

Cited by 37 publications

References 33 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

Pharmacomodulation of microRNA Expression in Neurocognitive Diseases: Obstacles and Future Opportunities

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

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