Overcoming the Blood-Brain Barrier, Strategies and Advances in Therapeutic Delivery: A Literature Review
Bibliographic record
Abstract
The treatment options for disorders affecting the central nervous system (CNS) heavily rely on medications to be delivered to the brain, however diverse and effective treatment options are lacking, especially in Alzheimer’s disease (AD) and brain cancers. The passage of drugs into the brain is challenging, due to limited permeability of the blood-brain barrier (BBB). The BBB is a physiological filter for molecules circulating in the bloodstream, playing an essential role in protecting the brain and maintaining its homeostasis. The endothelial cells constituting the microvasculature of the BBB exhibit characteristics such as high levels of tight junctions, adherens junctions and efflux transport proteins, which, together with the lack of capillary fenestrations, impede the ability of drugs to reach CNS targets. Currently available treatments are limited, with invasive neurosurgical interventions and novel non-invasive delivery strategies. Invasive approaches are challenged by significant adverse events and potentially marginal efficacy. Many new methods open prospects for targeted drug deposition in the brain, each with distinct mechanisms of action. These methods comprehend focused ultrasound-mediated disruption of the BBB, innovative physicochemical drug formulations and intranasal pharmacological administrations. The aim of this review is to provide a critical analysis of the current state of drug delivery across the BBB, comparing existing and emerging technologies in the context of neurodegenerative disorders, in particular AD, and brain cancers. A literature search was performed including articles exploring current and evolving methods for drug delivery across the BBB. Considering epidemiological trends highlighting the growing societal burden of neurodegeneration in aging populations and rising incidence of cancers worldwide, it is essential to explore options for effective drug delivery to the brain. The development and optimization of such innovative drug delivery methods holds significant potential for treating neurological disorders: facilitating the use of large molecules, exhibiting more specific cellular targeting but reduced brain permeability, or expediting the formulation of novel molecules bypassing the physiological systems of the BBB. These strategies can improve therapeutic outcomes, reduce side effects, and enhance the quality of life for patients affected with CNS diseases. Continued research is essential to refine and translate these techniques for clinical use.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.005 | 0.005 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".