![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
ABSTRACT
Introduction
The current treatment modalities available for Parkinson’s disease (PD) prove inadequate due to the inherent constraints in effectively transporting bioactive compounds across the blood-brain barrier. The utilization of synergistic combinations of multiple drugs in conjunction with advanced nanotechnology, emerges as a promising avenue for the treatment of PD, offering potential breakthroughs in treatment efficacy, targeted therapy, and personalized medicine.
Areas covered
This review provides a comprehensive analysis of the efficacy of multifactorial interventions for PD, simultaneously addressing the primary challenges of conventional therapies and highlighting how advanced technologies can help overcome these limitations. Part II focuses on the effectiveness of nanotechnology for improving pharmacokinetics of conventional therapies, through the synergistic use of dual or multiple therapeutic agents into a single nanoformulation. Significant emphasis is laid on the advancements toward innovative integrations, such as CRISPR/Cas9 with neuroprotective agents and stem cells, all effectively synergized with nanocarriers.
Expert opinion
By using drug combinations, we can leverage their combined effects to enhance treatment efficacy and mitigate side effects through lower dosages. This article is meant to give nanocarrier-mediated co-delivery of drugs and the strategic incorporation of CRISPR/Cas9, either as an independent intervention or synergized with a neuroprotective agent.
Article highlights
Given the resistance to existing treatments and the involvement of multiple pathways in nigrostriatal dopaminergic neuronal loss, it emphasizes the need for the adoption of combination therapy, along with nanotechnology advanced strategies, in modern treatment protocols for PD, to improve both safety and efficacy.
The article carefully reviews combination drug delivery strategies, representing a promising approach to target complex molecular pathways underlying disease manifestation. With insights from vast studies, it emphasizes the significance of nanocarrier systems in co-delivering treatments, focusing on strategic selection of drugs from same class or with common pathological features, allowing integrated therapeutic interventions via a consolidated mechanism.
The review encompasses a concise table comparing nanocarriers used in combination therapy for specifically PD brain drug delivery, summarizing their key advantages, limitations, and challenges. It also addresses Strategic Formulation Adjustments to further refine and guide future formulation strategies.
The article thoroughly elucidates the innovative integration of CRISPR/Cas9 technology with neuroprotective agents, both synthetic and natural, and outlines the recent advancements moving toward the inclusion of stem cells for optimized therapeutic interventions.
It contains the patents focusing on the field of PD, particularly combination therapies and their use for the treatment of PD.
This box encapsulates the salient features of the article, providing a concise yet comprehensive overview of the key takeaways.
List of abbreviations
| PD | = | Parkinson’s Disease |
| SNc | = | Substantia nigra pars compacta |
| CNS | = | Central nervous system |
| LBs | = | Lewy bodies |
| Parkin | = | Parkinson juvenile disease protein 2 |
| LRRK2 | = | Leucine-rich repeat kinase 2 |
| PINK1 | = | PTEN-induced kinase 1 |
| DJ1 or PARK7 | = | Parkinsonism-associated deglycase protein |
| DAT | = | Dopamine active transporter |
| DA | = | Dopamine |
| ROS | = | Reactive oxygen species |
| MPTP | = | 1-methyl-4-phenyl-2,3,6-tetrahydropyridine |
| L-Dopa | = | Levodopa |
| BBB | = | Blood-brain barrier |
| RES | = | Resveratrol |
| EGCG | = | Epigallocatechin-3-gallate |
| TNF | = | Tumor necrosis factor |
| QOL | = | Quality of life |
| EYPC | = | Egg-yolk phosphatidylcholine |
| PEG | = | Polyethylene glycol |
| NE | = | Nano-emulsions |
| SLN | = | Solid lipid nanoparticle |
| NLC | = | Nanostructured lipid carrier |
| SLNs | = | Solid lipid nanoparticles |
| NLCs | = | Nanostructured lipid carriers |
| GNLs | = | Gelatin NLC |
| bFGF | = | Basic fibroblast growth factor |
| GB | = | Ginkgolide B |
| PAMAM | = | Poly (amido amine) |
| NR | = | Nicotinamide riboside |
| SAM | = | S-adenosyl methionine |
| SV2A | = | Synaptic vesicle glycoprotein 2A |
| CPP | = | Carboxypiperazin -4-yl) propyl-1-phosphoric acid |
| GDNF | = | Glial cell line-derived neutrophic factor |
| BDNF | = | Brain-derived neutrophic factor |
| ANG | = | Angiopep-2 |
| MWCNTs | = | Multiwalled carbon nanotubes |
| PEI | = | Polyethylenimines |
| siRNA | = | Small interfering RNA |
| HDR | = | Homology-directed repair |
| ABEs | = | Adenine base editors |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.