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

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

Asian Journal of Pharmaceutical Sciences ◽

10.1016/j.ajps.2017.11.004 ◽

2018 ◽

Vol 13 (6) ◽

pp. 507-517 ◽

Cited By ~ 10

Author(s):

Nrupa Borkar ◽

Huiling Mu ◽

René Holm

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Parkinson's Disease ◽

Drug Delivery Systems ◽

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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Development of Innovative Orally Fast Disintegrating Film Dosage Forms: A Review

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2012.5.2.2 ◽

2012 ◽

Vol 5 (2) ◽

pp. 1666-1674 ◽

Cited By ~ 3

Author(s):

Bibhu Prasad Panda ◽

N.S Dey ◽

M.E.B. Rao

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Dosage Form ◽

Geriatric Patients ◽

Dosage Forms ◽

Delivery Systems ◽

Design And Development ◽

Innovative Drug ◽

Potential Benefits ◽

Pharmaceutical Industries

Over the past few decades, there has been an increased interest for innovative drug delivery systems to improve safety, efficacy and patient compliance, thereby increasing the product patent life cycle. The discovery and development of new chemical entities is not only an expensive but also time consuming affair. Hence the pharmaceutical industries are focusing on the design and development of innovative drug delivery systems for existing drugs. One such delivery system is the fast disintegrating oral film, which has gained popularity among pediatric and geriatric patients. This fast disintegrating film with many potential benefits of a fast disintegrating tablet but devoid of friability and risk of choking is more acceptable to pediatric and geriatric patients. Formulation of fast disintegrating film can be achieved by various techniques, but common methods of preparation include spraying and casting. These film forming techniques use hydrophilic film former in combination with suitable excipients, which allow the film to disintegrate or dissolve quickly in the mouth within a few seconds without the administration of water. In view of the advantages of the fast disintegrating films over the fast disintegrating tablets and other dosage forms, it has the potential for commercial exploitation. The oral film dosage form not only has certain advantages of other fast disintegrating systems but also satisfies the unmet needs of the market. The present review emphasizes on the potential benefits, design and development of robust, stable, and innovative orally fast- disintegrating films and their future scenarios on a global market as a pharmaceutical dosage form.

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Chitosan-based Polymer Matrix for Pharmaceutical Excipients and Drug Delivery

Current Medicinal Chemistry ◽

10.2174/0929867325666180927100817 ◽

2019 ◽

Vol 26 (14) ◽

pp. 2502-2513 ◽

Cited By ~ 9

Author(s):

Md. Iqbal Hassan Khan ◽

Xingye An ◽

Lei Dai ◽

Hailong Li ◽

Avik Khan ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Drug Carrier ◽

Drug Loading ◽

Delivery Systems ◽

Cancer Drug ◽

Release Mechanism ◽

Innovative Drug ◽

Pharmaceutical Excipients ◽

Weight Variation

The development of innovative drug delivery systems, versatile to different drug characteristics with better effectiveness and safety, has always been in high demand. Chitosan, an aminopolysaccharide, derived from natural chitin biomass, has received much attention as one of the emerging pharmaceutical excipients and drug delivery entities. Chitosan and its derivatives can be used for direct compression tablets, as disintegrant for controlled release or for improving dissolution. Chitosan has been reported for use in drug delivery system to produce drugs with enhanced muco-adhesiveness, permeation, absorption and bioavailability. Due to filmogenic and ionic properties of chitosan and its derivative(s), drug release mechanism using microsphere technology in hydrogel formulation is particularly relevant to pharmaceutical product development. This review highlights the suitability and future of chitosan in drug delivery with special attention to drug loading and release from chitosan based hydrogels. Extensive studies on the favorable non-toxicity, biocompatibility, biodegradability, solubility and molecular weight variation have made this polymer an attractive candidate for developing novel drug delivery systems including various advanced therapeutic applications such as gene delivery, DNA based drugs, organ specific drug carrier, cancer drug carrier, etc.

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