Development of Brain Permeable Drugs and Novel Strategies to Overcome the Brain Barriers for Treatment Purposes

Apr 23, 2025Current pharmaceutical design

Creating Brain-Accessible Drugs and New Ways to Bypass Brain Barriers for Treatment

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

The Blood-Brain Barrier (BBB) presents significant challenges for delivering therapeutic agents to the Central Nervous System (CNS) due to its selective nature.

The BBB regulates molecular exchange between the circulatory system and the CNS, protecting the brain from harmful substances.
Drug properties such as lipophilicity, molecular weight, and hydrogen bonding affect their ability to penetrate the BBB.
Current strategies to improve drug delivery include nanotechnology-based carriers and receptor-mediated transcytosis.
Emerging methods like focused ultrasound with microbubbles and intranasal delivery show potential for bypassing BBB restrictions.
Gene therapy using viral and nonviral vectors may help address genetic disorders affecting the CNS.
Challenges such as off-target effects and limited delivery efficiency need to be addressed for successful clinical application.

AI simplified

The Blood-Brain Barrier (BBB), a dynamic and highly selective interface, regulates the exchange of molecules between the circulatory system and the Central Nervous System (CNS). While it protects the brain from toxins and pathogens, it also restricts the delivery of therapeutic agents, posing a significant challenge in treating CNS disorders such as Alzheimer's disease, Parkinson's disease, and glioblastoma. This manuscript explores the structural and functional complexity of the BBB, including the roles of tight junctions, adherens junctions, astrocytes, pericytes, and endothelial cells. It highlights the influence of drug physicochemical properties, such as lipophilicity, molecular weight, and hydrogen bonding, on BBB penetration. Current strategies to enhance drug delivery include nanotechnology-based carriers (liposomes, solid lipid nanoparticles, polymer-based carriers), receptor-mediated transcytosis, and cell-penetrating peptides. Emerging approaches like focused ultrasound with microbubbles, intranasal delivery, and exosome-mediated transport demonstrate significant potential for bypassing BBB constraints. Gene therapy, employing both viral and nonviral vectors, offers promise for addressing genetic CNS disorders. Despite advances, limitations, such as offtarget effects, limited delivery efficiency, and potential toxicity, remain critical barriers to clinical translation. Future research must prioritize multidisciplinary approaches integrating nanotechnology, personalized medicine, and enhanced understanding of BBB biology. Innovations in non-invasive, targeted delivery systems are essential to overcoming existing challenges and enabling effective treatment of CNS disorders. This review underscores the need for further exploration of these technologies to achieve sustained, site-specific drug delivery, thereby advancing therapeutic interventions for neurological diseases. The blood-brain barrier (BBB) is a critical interface that protects the brain but limits drug delivery, posing challenges in treating CNS disorders. Advancing multidisciplinary approaches and innovative delivery systems is essential to overcome these limitations and enable effective therapies for neurological diseases.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗View full text ↗

Development of Brain Permeable Drugs and Novel Strategies to Overcome the Brain Barriers for Treatment Purposes

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief