Improving drug delivery technology for treating neurodegenerative diseases

ABSTRACT

Introduction: Neurodegenerative diseases (NDs) represent intricate challenges for efficient uptake and transport of drugs to the brain mainly due to the restrictive blood-brain barrier (BBB). NDs are characterized by the loss of neuronal subtypes as sporadic and/or familial and several mechanisms of neurodegeneration have been identified.

Areas covered: This review attempts to recap, organize and concisely evaluate the advanced drug delivery systems designed for treating common NDs. It highlights key research gaps and opinionates on new neurotherapies to overcome the BBB as an addition to the current treatments of countering oxidative stress, inflammation and apoptotic mechanisms.

Expert Opinion: Current treatments do not fully address the biological, drug and therapeutic factors faced. This has led to the development of vogue treatments such as nose-to-brain technologies, bio-engineered systems, fusion protein chaperones, stem cells, gene therapy, use of natural compounds, neuroprotectants and even vaccines. However, failure of these treatments is mainly due to the BBB and non-specific delivery in the brain. In order to increase neuroavailability various advanced drug delivery systems provide promising alternatives that are able to augment the treatment of Alzheimer’s disease and Parkinson’s disease. However, much work is still required in this field beyond the preclinical testing phase.

KEYWORDS:

• Advanced drug delivery
• blood-brain barrier
• gene therapy
• nanotechnology
• neuroavailability
• neuroregeneration
• neurodegenerative diseases
• polymer implants
• proteins
• scaffolds
• stem cells
• vaccines

Article highlights

• Neuroavailability depends on optimal drug absorption from the site of administration and its penetration across the BBB. For these processes to be favorable, advanced drug delivery systems are required to provide site-specific drug delivery to the brain.

• Predicting drug permeation across the BBB using in vitro permeability assays and computational models should be integrated early on in the drug development process.

• Drugs can essentially be delivered to the brain via a myriad of routes that comprise (I) direct delivery (intracerebral, intraventricular, or intrathecal), (II) systemically (intra-arterial or intravenous), and (III) intranasally.

• The physicochemical versatility and size of nanocarriers facilitate drug encapsulation and transport across the BBB. The function of nanocarriers is affected by size, drug entrapment efficiency, shape, brain targeting efficiency, and the route of administration.

• The correlation of in vitro to in vivo experimentation for drug delivery to the brain is rather challenging, and almost always, results do not provide adequate mimicry due to many biological obstacles and scarcity of adequate in vitro models to replicate the BBB.

• In order to achieve sufficient neuroavailability of drugs across the BBB and subsequent drug targeting within specific regions of the brain, parenchyma neuroactive drugs need to accumulate in the brain in a sufficient and sustained manner.

• 3D-bioprinting may play a central role in developing precise in vitro model for assessing the performance of advanced drug delivery systems for NDs and also as a neuroactive drug screening tool by serving as a foundation for other brain-related disease models.

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Declaration of interest

This work was funded by the National Research Foundation (NRF) of South Africa. The authors have no other 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 apart from those disclosed.