Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To review approaches for enhancing transport across or bypassing the blood–brain barrier for brain cancer therapy, including biochemical drug/nanocarrier modifications, local delivery methods, and focused ultrasound with microbubbles.

Disease model brain cancer

Cargo name and characteristics Small-molecule cancer therapeutics; biological cancer therapeutics (proteins/antibodies); drug nanocarriers/nanoparticles (engineered nanoparticle drug carriers)

Outcomes and Safety

Summary of Outcomes The review concludes that biochemical modification of drugs/nanocarriers, receptor-mediated targeting, local delivery methods, and focused ultrasound (FUS) with microbubbles can enhance or bypass the blood–brain barrier to enable local, noninvasive delivery of small molecules and biological cancer therapeutics, with clinical trials showing promise. The paper does not report specific FUS parameter sets or identify particular ultrasound parameters as successful.

Safety-related matter No safety concerns or adverse effects are mentioned in the provided text.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

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