Intraparenchymal Drug Delivery for Parkinson’s Disease

Author(s):  
R. D. Penn ◽  
A. A. Linninger
2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  

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.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen Gasca-Salas ◽  
Beatriz Fernández-Rodríguez ◽  
José A. Pineda-Pardo ◽  
Rafael Rodríguez-Rojas ◽  
Ignacio Obeso ◽  
...  

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.


2015 ◽  
Vol 23 (9) ◽  
pp. 775-788 ◽  
Author(s):  
Abhijeet D. Kulkarni ◽  
Yogesh H. Vanjari ◽  
Karan H. Sancheti ◽  
Veena S. Belgamwar ◽  
Sanjay J. Surana ◽  
...  

2021 ◽  
Vol 11 (22) ◽  
pp. 10727
Author(s):  
Ezgi Saylam ◽  
Yigit Akkaya ◽  
Elif Ilhan ◽  
Sumeyye Cesur ◽  
Ece Guler ◽  
...  

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.


2020 ◽  
Author(s):  
wenkai zhou ◽  
Chang Liu ◽  
Feifei Yu ◽  
Xia Niu ◽  
Xiaomei Wang ◽  
...  

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.


Biomaterials ◽  
2016 ◽  
Vol 102 ◽  
pp. 72-86 ◽  
Author(s):  
Juan Li ◽  
Mohammadali Darabi ◽  
Jingjing Gu ◽  
Junbin Shi ◽  
Jinhua Xue ◽  
...  

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