Challenges and trends in apomorphine drug delivery systems for the treatment of Parkinson's disease

As per the present global scenario, Parkinson’s disease (PD) is considered to be the second most common neurodegenerative disorder which is a keen area of interest among researchers. The conventional therapies generally employed against PD are associated with serious drawbacks including limited transport across selectively permeable BBB, hepatic metabolism, intestinal barrier, etc. This urges the need to develop novel therapeutic alternatives. The oral route being the most preferred route of administration needs to be explored for new and more intelligent drug delivery systems. Nanotechnology has been proposed to play a promising role in reversing the progression of the disease via the oral route. Nanocarriers, namely nanoparticles, lipid nanoparticles, nanoemulsions, nanocrystals, nanomicellar formulations, self-nanoemulsifying drug delivery systems and alginate nanocomposites have been investigated upon to modulate the fate of drugs inside the human body when administered orally. The development of various nanotherapeutics for the treatment of PD has been reviewed, depicting an enhanced bioavailability to provide a desired therapeutic outcome. The new advances in the therapy have been explored and highlighted through the body of this review. However, a therapeutically effective concentration at the target site remains a challenge, therefore extensive exploration in the field of nanotherapeutics may facilitate superior drug delivery to CNS via oral route thereby improving the state of disease progression.

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Applications of Exosomes in Targeted Drug Delivery for the Treatment of Parkinson’s Disease: A Review of Recent Advances and Clinical Challenges

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666201019112557 ◽

2020 ◽

Vol 20 (30) ◽

pp. 2777-2788

Author(s):

Bhumika Kumar ◽

Mukesh Pandey ◽

Faizana Fayaz ◽

Tareq Abu Izneid ◽

Faheem Hyder Pottoo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Mammalian Cells ◽

Drug Delivery Systems ◽

Drug Carrier ◽

Delivery Systems ◽

Brain Targeting ◽

The Brain

Parkinson’s disease (PD) is one of the most prevalent and severe neurodegenerative disease affecting more than 6.1 million people globally. It is characterized by age-related progressive deterioration of neurological functions caused by neuronal damage or neuronal death. During PD, the dopamineproducing cells in the substantia nigra region of the brain degenerate, which leads to symptoms like resting tremors and rigidity. Treatment of PD is very challenging due to the blood-brain barrier, which restricts the drug from reaching the brain. Conventional drug delivery systems possess a limited capacity to cross the blood barrier, leading to low bioavailability and high toxicity (due to off-site drug release). Therefore, it becomes necessary to accelerate the development of novel drug delivery systems, including nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, and solid lipid nanoparticles for the treatment of PD. Exosomes are biological lipid bilayer membrane vesicles produced by nearly all mammalian cells. The characteristics of vesicles are unique to their cell of origin and are primarily involved in intracellular communication. Exosomes, due to their nanoscale size, could easily permeate across the central nervous system, which makes them ideal for targeting the neurons in the substantia nigra. Exosomes could be efficient drug carrier systems for brain targeting, which can increase the efficacy of the drug and minimize the side effects. The review aims at providing a broad updated view of exosomes and their application in the treatment of PD.

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Potential of microemulsified entacapone drug delivery systems in the management of acute Parkinson's disease

Journal of Acute Disease ◽

10.1016/j.joad.2016.05.004 ◽

2016 ◽

Vol 5 (4) ◽

pp. 315-325 ◽

Cited By ~ 7

Author(s):

Harini Chowdary Vadlamudi ◽

Prasanna Raju Yalavarthi ◽

Basaveswara Rao Mandava Venkata ◽

Jyotsna Thanniru ◽

Vandana K.R. ◽

...

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease ◽

Drug Delivery Systems ◽

Delivery Systems

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

Maturitas ◽

10.1016/j.maturitas.2013.05.019 ◽

2013 ◽

Vol 76 (3) ◽

pp. 272-278 ◽

Cited By ~ 47

Author(s):

E. Garbayo ◽

E. Ansorena ◽

M.J. Blanco-Prieto

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease ◽

Drug Development ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Innovative Drug

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New non-oral drug delivery systems for Parkinson's disease treatment

Expert Opinion on Drug Delivery ◽

10.1517/17425247.2011.556616 ◽

2011 ◽

Vol 8 (3) ◽

pp. 359-374 ◽

Cited By ~ 17

Author(s):

Shadab Md ◽

Shadabul Haque ◽

Jasjeet Kaur Sahni ◽

Sanjula Baboota ◽

Javed Ali

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease ◽

Drug Delivery Systems ◽

Oral Drug Delivery ◽

Delivery Systems ◽

Oral Drug ◽

Disease Treatment ◽

Oral Drug Delivery Systems

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Application of neurotoxin- and pesticide-induced animal models of Parkinson’s disease in the evaluation of new drug delivery systems

Acta Pharmaceutica ◽

10.2478/acph-2022-0008 ◽

2021 ◽

Vol 72 (1) ◽

pp. 35-58

Author(s):

Yaquelyn Casanova ◽

Sofia Negro ◽

Emilia Barcia

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease ◽

Animal Models ◽

Drug Delivery Systems ◽

Unmet Need ◽

Delivery Systems ◽

New Drug ◽

6 Hydroxydopamine ◽

New Treatments

Abstract Parkinson’s disease (PD) is the second most prevalent neuro-degenerative disease after Alzheimer´s disease. It is characterized by motor symptoms such as akinesia, bradykinesia, tremor, rigidity, and postural abnormalities, due to the loss of nigral dopaminergic neurons and a decrease in the dopa-mine contents of the caudate-putamen structures. To this date, there is no cure for the disease and available treatments are aimed at controlling the symptoms. Therefore, there is an unmet need for new treatments for PD. In the past decades, animal models of PD have been proven to be valuable tools in elucidating the nature of the pathogenic processes involved in the disease, and in designing new pharmacological approaches. Here, we review the use of neurotoxin-induced and pesticide-induced animal models of PD, specifically those induced by rotenone, paraquat, maneb, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-OHDA (6-hydroxydopamine), and their application in the development of new drug delivery systems for PD.

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Novel drug delivery systems of β2 adrenoreceptor agonists to suppress SNCA gene expression and mitochondrial oxidative stress in Parkinson’s disease management

Expert Opinion on Drug Delivery ◽

10.1080/17425247.2020.1779218 ◽

2020 ◽

Vol 17 (8) ◽

pp. 1119-1132

Author(s):

Piyong Sola ◽

Praveen Krishnamurthy ◽

Pavan Kumar Chintamaneni ◽

Sai Kiran S.S Pindiprolu ◽

Mamta Kumari

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Parkinson’S Disease ◽

Drug Delivery ◽

Disease Management ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Mitochondrial Oxidative Stress ◽

Snca Gene ◽

Novel Drug

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Cyclodextrins in Parkinson’s Disease

Biomolecules ◽

10.3390/biom9010003 ◽

2018 ◽

Vol 9 (1) ◽

pp. 3 ◽

Cited By ~ 4

Author(s):

Marisa C. F. Barros ◽

Ana C. F. Ribeiro ◽

Miguel A. Esteso

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Aqueous Solutions ◽

Molar Volume ◽

Partial Molar Volume ◽

Diffusion Coefficients ◽

Dopaminergic Neurons ◽

Drug Delivery Systems ◽

Controlled Drug Delivery ◽

Delivery Systems

: Parkinson’s disease is a movement disorder characterized by a progressive degeneration of dopaminergic neurons that has been object of study by the scientific community through the last decades. However, nowadays there is still no treatment to cure it, although there are drugs available, with limited efficacy, to relieve the symptoms or replenish the cells with dopamine to supply the lack of dopaminergic neurons. This work was structured in two parts. In the first one, binary aqueous solutions of L-dopa and cyclodextrins were studied. In the second part, ternary aqueous solutions of L-dopa were studied with each of the selected cyclodextrins. In all cases, thermodynamic properties (density, partial molar volume and thermodynamic transfer functions for temperatures between 294.15 ± 0.01 K and 312.15 ± 0.01 K) and transport properties (mutual diffusion coefficients, viscosity, transfer viscosity at 298.15 ± 0.01 K and 310.15 ± 0.01 K) were studied. Using theoretical models to adjust the experimental data obtained for the diffusion coefficients and for the apparent molar volumes, in the ternary aqueous solutions, it was possible to estimate the values to the L-dopa-cyclodextrin association constant. For the aqueous ternary solutes, the partial molar volume of transfer of levodopa in the presence of the cyclodextrins, the partial molar expansibility at infinite dilution and from this, the Hepler constant, were determined. Also, the values of Gibbs free energy (ΔG0), enthalpy (ΔH0) and entropy (ΔS0) were determined. From the obtained information, it was possible to characterize the molecular interactions, as well as to identify some structural characteristics of the controlled drug delivery systems under study and to estimate the influence of the cyclodextrin substituent groups, and, also, the temperature effect in the interaction levodopa-cyclodextrin. It is our intent to attain information about the mechanism of possible new systems for controlled drug delivery systems, throughout an alternative perspective, which could allow to increase its effectiveness in the Parkinson’s treatment.

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