Abstract
Treatment of brain tumors is challenging since the blood–brain tumor barrier prevents chemotherapy drugs from reaching the tumor site in sufficient concentrations. Nanomedicines have great potential for therapy of brain disorders but are still uncommon in clinical use despite decades of research and development. Here, we provide an update on nano-carrier strategies for improving brain drug delivery for treatment of brain tumors, focusing on liposomes, extracellular vesicles and biomimetic strategies as the most clinically feasible strategies. Finally, we describe the obstacles in translation of these technologies including pre-clinical models, analytical methods and regulatory issues.
Highlights
The barrier is formed from interlinked brain endothelial cells (BECs) supported by pericytes and astrocyte end feet, which cover the majority of BEC surface area
This review focuses on the barrier properties and methods for bypassing, penetrating or disrupting the blood–brain barrier (BBB) for drug delivery
Smaller nanocarriers (20 nm) were able to accumulate in the early stages of tumor development, whereas 100 nm nanocarriers could not cross the blood–brain tumor barrier (BBTB) until later stages, which correlated with greater tumor leakiness
Summary
The blood–brain barrier (BBB) is a complex semi-permeable interface which separates the brain parenchyma from systemic blood circulation at the microvascular level. A diverse array of multi-substrate efflux pumps including ABCB1/MDR1 (p-glycoprotein), ABCC1 (MRP1) and BCRP/ABCG2, actively transport unwanted substances back to the luminal side, including most drugs of potential value for neurological disorders [11]. These transporters are widely expressed, on BECs, and on astrocytes, neurons, microglia and pericytes. Luminal and abluminal sides have specific expression patterns, which vary by brain locale, forming a heterogenous interface for molecule passage [12] Adding to this complexity, there is considerable BBB heterogeneity throughout different brain regions, variation by routes of administration, and variations due to disease state [7,13]
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