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

Abstract

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.

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson’s disease

“…That is why many studies focus on designing different drug delivery systems to enhance the release of these proteins into the brain tissue, either through invasive or noninvasive methods. 31,32 Considerable attention has been paid to the improvement of PLGA nanoparticles, making the local delivery of neuroprotective agents into the brain possible. In fact, PLGA NS can preserve the encapsulated unstable therapeutic drug from enzyme degradation, release the drug in a controlled and continuous manner, enhance its biodistribution, and permit drug targeting.…”

Nanoparticular Drug Delivery Systems in the Treatment Central Nervous System Diseases: Review

“…26,31 Ancak, L-Dopa %30 gibi düşük bir oral biyoyararlanıma sahiptir ve KBB'yi geçebilse bile periferik bölgelerdeki aromatik aminoasit dekarboksilaz enzimi tarafından degrade olmaktadır. 26,31 Bu durum hastalara hedef doku için gerekenden daha yüksek dozda ilaç yüklenmesine neden olmakta, ayrıca hasta olmayan periferik dokular da L-Dopa ve dopaminin etkilerine maruz kalmaktadır. Karbidopa, L-Dopa'nın periferdeki kullanımını azaltmak ve beyne ulaşan miktarını arttırmak için kullanılmaktadır, fakat tamamen başarıya ulaşılamamaktadır.…”

“…8,29,32 Kısa etki süresine sahip konvansiyonel preparatların aksine, reseptörlerin sü-rekli bir şekilde uyarılmasını sağlayan kontrollü salım sistemleri, L-Dopa kaynaklı diskinezilerin azaltılması açısından etkin bir yöntem olarak düşü-nülebilmektedir. 26,30,31 Nano boyuttaki ilaç taşıyıcı sistemler, içerisine yüklenen etken maddeyi dış ortamdan izole ederek enzimatik degredasyondan korunmasını sağ-lamaktadır, bu avantajdan Parkinson hastalığı tedavisinde L-Dopa'nın istenen bölgeye hedeflenmesini sağlayarak periferik dokular üzerindeki yan etkilerinin azaltılması ve beyne istenen dozda ulaş-ması amacıyla yararlanılabilmektedir.…”

Untitled

“…42 The fascinating thing about INDD is that the drugs can be delivered to the brain bypassing the blood brain barrier and helps in the treatment of various neurodegenerative diseases. This strategic delivery routes is found to be advantageous in-Alzheimer's disease, Epilepsy, Parkinson's disease, or pain 43 where rapid or/and targeted delivery of therapeutics is required.…”