New routes of dopaminergic drug delivery in patients with Parkinson's disease

2020 ◽  
Vol 19 (2) ◽  
pp. 105-106
Author(s):  
Angelo Antonini
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Dopaminergic Drug

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

scholarly journals Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen Gasca-Salas ◽  
Beatriz Fernández-Rodríguez ◽  
José A. Pineda-Pardo ◽  
Rafael Rodríguez-Rojas ◽  
Ignacio Obeso ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Neurodegenerative Disorders ◽  
Focused Ultrasound ◽  
Temporal Cortex ◽  
Clinical State ◽  
Cognitive Improvement ◽  
Bbb Opening

AbstractMR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.

scholarly journals A survey into the influence of dopaminergic drug exposure on ‘sense of presence’ symptoms in patients with parkinson's disease

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S279-S280
Author(s):  
Emma Padfield ◽  
Hannah Potticary ◽  
Tim Segal
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Regression Analysis ◽  
Drug Exposure ◽  
Drug Dosage ◽  
Equivalent Dose ◽  
Dopaminergic Medication ◽  
Dopaminergic Drug ◽  
Sense Of Presence ◽  
The Relationship

AimsThe first objective was to estimate prevalence of sense of presence (SoP) experiences in patients with Parkinson's Disease (PD), including whether onset was prior to or after commencing dopaminergic medication. The second objective was to explore the relationship between frequency of SoP experiences and dopaminergic drug, drug dosage and length of drug exposure. The experimental hypothesis was that SoP symptoms in PD would present more frequently in patients treated longer and with higher dopaminergic drug doses.BackgroundPD is a debilitating neurodegenerative disorder. Psychiatric symptoms are common and associated with impaired quality of life and higher treatment costs. PD psychosis often starts with ‘minor hallucinations’, the most common being a false ‘sense of presence’ (SoP), the vivid sensation that someone else is nearby when nobody is there. SoP symptoms typically do not cause significant distress but may act as a prognostic marker for future severe psychosis and may prompt alteration of treatment or reduction in dopaminergic drug dosage. This study aimed to extend prior research by characterizing SoP further and investigating the link with dopaminergic medication.MethodThis was a retrospective, cross-sectional study. Twenty-one patients diagnosed with PD completed a questionnaire to identify presence of SoP symptoms, duration of symptoms, timing of onset related to dopaminergic treatment and the frequency of symptoms in relation to current levodopa equivalent dose (LED). Descriptive frequencies were compared using a two-tailed t-test. Multiple regression analysis was conducted to assess the relationship between frequency of SP experiences, levodopa equivalent dose and length of drug exposure.ResultSixteen of twenty-one patients reported experiencing SoP symptoms. Patients who had not experienced SoP symptoms had a significantly lower LED than those who had experienced these symptoms. There were no other significant differences between the groups. No statistical significance was shown on regression analysis; however our study was not adequately powered for the regression analysis as the number of participants was too low.ConclusionThis study confirms that SoP symptoms are common among patients with PD and supports a correlation between the total daily equivalent dose of levodopa and SoP symptoms. It does not provide evidence for a temporal relationship between onset of SoP symptoms and duration of dopaminergic treatment. The study was insufficiently powered and a larger study is required to investigate further.

Nanotechnology-mediated nose to brain drug delivery for Parkinson's disease: a mini review

2015 ◽  
Vol 23 (9) ◽  
pp. 775-788 ◽  
Author(s):  
Abhijeet D. Kulkarni ◽  
Yogesh H. Vanjari ◽  
Karan H. Sancheti ◽  
Veena S. Belgamwar ◽  
Sanjay J. Surana ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Brain Drug Delivery

scholarly journals Levodopa-Loaded 3D-Printed Poly (lactic) Acid/Chitosan Neural Tissue Scaffold as a Promising Drug Delivery System for the Treatment of Parkinson’s Disease

2021 ◽  
Vol 11 (22) ◽  
pp. 10727
Author(s):  
Ezgi Saylam ◽  
Yigit Akkaya ◽  
Elif Ilhan ◽  
Sumeyye Cesur ◽  
Ece Guler ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Tissue Engineering ◽  
Parkinson's Disease ◽  
Drug Delivery System ◽  
Delivery System ◽  
Neural Tissue ◽  
Fickian Diffusion ◽  
Pore Sizes ◽  
3D Printed

Parkinson’s disease, the second most common neurodegenerative disease in the world, develops due to decreased dopamine levels in the basal ganglia. Levodopa, a dopamine precursor used in the treatment of Parkinson’s disease, can be used as a drug delivery system. This study presents an approach to the use of 3D-printed levodopa-loaded neural tissue scaffolds produced with polylactic acid (PLA) and chitosan (CS) for the treatment of Parkinson’s disease. Surface morphology and pore sizes were examined by scanning electron microscopy (SEM). Average pore sizes of 100–200 µm were found to be ideal for tissue engineering scaffolds, allowing cell penetration but not drastically altering the mechanical properties. It was observed that the swelling and weight loss behaviors of the scaffolds increased after the addition of CS to the PLA. Levodopa was released from the 3D-printed scaffolds in a controlled manner for 14 days, according to a Fickian diffusion mechanism. Mesenchymal stem cells (hAD-MSCs) derived from human adipose tissue were used in MTT analysis, fluorescence microscopy and SEM studies and confirmed adequate biocompatibility. Overall, the obtained results show that PLA/CS 3D-printed scaffolds have an alternative use for the levodopa delivery system for Parkinson’s disease in neural tissue engineering applications.

scholarly journals Co-loading of Levodopa and Curcumin Using Brain-targeted Protocells as a Drug Delivery System for Improving the Efficacy of Parkinson's Disease

2020 ◽  
Author(s):  
wenkai zhou ◽  
Chang Liu ◽  
Feifei Yu ◽  
Xia Niu ◽  
Xiaomei Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Inner Core ◽  
Cell Model ◽  
Mesoporous Silica Nanoparticles ◽  
Brain Targeting ◽  
Delivery Platform ◽  
A Cell

Abstract Parkinson's disease (PD), one of the most common movement and neurodegenerative disorders, is challenging to treat, partly because the blood-brain barrier blocks passage of most drugs. Levodopa is a common clinical drug for controlling the symptoms of PD, but it only replenishes the missing dopamine, can’t protect dopaminergic neurons. While curcumin as a neuroprotective agent has been reported for treatment of PD. Herein, we present a novel organic-inorganic composite nanoparticle with brain targeting (denoted as lf-protocells) for co-delivery of levodopa and curcumin, and demonstrate its attractive use as a biocompatible platform for PD treatment. The nanoparticle system is comprised of a lactoferrin (lf) modified lipid bilayer (LB) containing curcumin as its outer membrane and mesoporous silica nanoparticles (MSNs) containing levodopa as its supporting inner core. Our studies illustrate that the lf-protocells have a size of about 180 nm and spherical morphology, and can be used to co-load levodopa and curcumin efficiently. Further, a cell model and a mouse model induced by rotenone (Rot) and MPTP respectively are used to investigate the effects of binary-drug loaded lf-protocells on PD. Our results demonstrate that the combination of curcumin and levodopa alleviate the apoptosis of PD cells, enhance the cell viability as compared to levodopa used alone; levodopa together with curcumin also efficiently decrease the expression of a-synuclein, increase the expression of tyrosine hydroxylase in SH-SY5Y cells, and transform more levodopa into dopamine for supplement the loss of the brain. Moreover, the resulting binary-drug loaded lf-protocells ameliorate oxidative stress and mitochondrial dysfunction as compared to combination of free drugs. In addition, testing in a mouse model indicate that lf-protocells can improve significantly the motor function and distribution in brain compared with unmodified protocells. In conclusion, binary-drug loaded lf-protocells show much better therapeutic efficacy in both the cell model and the mouse model of PD and lower toxicity than bare MSNs. These results suggest that lf-protocells can be used as a promising drug delivery platform for targeted therapy against PD and other diseases of the central nervous system.

Sign in / Sign up

Export Citation Format

Share Document