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Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier

View Article: PubMed Central

ABSTRACT

The blood-brain barrier (BBB) poses a unique challenge for drug delivery to the central nervous system (CNS). The BBB consists of a continuous layer of specialized endothelial cells linked together by tight junctions, pericytes, nonfenestrated basal lamina, and astrocytic foot processes. This complex barrier controls and limits the systemic delivery of therapeutics to the CNS. Several innovative strategies have been explored to enhance the transport of therapeutics across the BBB, each with individual advantages and disadvantages. Ongoing advances in delivery approaches that overcome the BBB are enabling more effective therapies for CNS diseases. In this review, we discuss: (1) the physiological properties of the BBB, (2) conventional strategies to enhance paracellular and transcellular transport through the BBB, (3) emerging concepts to overcome the BBB, and (4) alternative CNS drug delivery strategies that bypass the BBB entirely. Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS.

No MeSH data available.


Strategies for delivering therapeutic agents across the BBB. Therapeutic agents are transported from the vessel lumen across the BBB via osmotic or chemical disruption of tight junctions, receptor-mediated transcytosis, nanoparticle-based carriers (including targeted nanoparticles), cell-mediated delivery, and FUS-mediated oscillation of microbubbles causing disruption of tight junctions and enhanced transcytosis. Interstitial wafers and microchips, in addition to catheter-based CED, bypass the BBB and deliver therapeutic agents directly to the brain parenchyma.
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Figure 1: Strategies for delivering therapeutic agents across the BBB. Therapeutic agents are transported from the vessel lumen across the BBB via osmotic or chemical disruption of tight junctions, receptor-mediated transcytosis, nanoparticle-based carriers (including targeted nanoparticles), cell-mediated delivery, and FUS-mediated oscillation of microbubbles causing disruption of tight junctions and enhanced transcytosis. Interstitial wafers and microchips, in addition to catheter-based CED, bypass the BBB and deliver therapeutic agents directly to the brain parenchyma.

Mentions: A number of strategies have been developed to overcome the BBB and improve the delivery of therapeutic agents to the brain (see Fig. 1). These range from disrupting the barrier itself to modifying the transported agents and their carriers. An alternative strategy is to deliver drugs directly into the brain through a variety of routes that bypass the BBB entirely. In this review, we discuss both conventional and emerging strategies to overcome the BBB, including specific features, advantages, and limitations (see Table 1).


Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier
Strategies for delivering therapeutic agents across the BBB. Therapeutic agents are transported from the vessel lumen across the BBB via osmotic or chemical disruption of tight junctions, receptor-mediated transcytosis, nanoparticle-based carriers (including targeted nanoparticles), cell-mediated delivery, and FUS-mediated oscillation of microbubbles causing disruption of tight junctions and enhanced transcytosis. Interstitial wafers and microchips, in addition to catheter-based CED, bypass the BBB and deliver therapeutic agents directly to the brain parenchyma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997920&req=5

Figure 1: Strategies for delivering therapeutic agents across the BBB. Therapeutic agents are transported from the vessel lumen across the BBB via osmotic or chemical disruption of tight junctions, receptor-mediated transcytosis, nanoparticle-based carriers (including targeted nanoparticles), cell-mediated delivery, and FUS-mediated oscillation of microbubbles causing disruption of tight junctions and enhanced transcytosis. Interstitial wafers and microchips, in addition to catheter-based CED, bypass the BBB and deliver therapeutic agents directly to the brain parenchyma.
Mentions: A number of strategies have been developed to overcome the BBB and improve the delivery of therapeutic agents to the brain (see Fig. 1). These range from disrupting the barrier itself to modifying the transported agents and their carriers. An alternative strategy is to deliver drugs directly into the brain through a variety of routes that bypass the BBB entirely. In this review, we discuss both conventional and emerging strategies to overcome the BBB, including specific features, advantages, and limitations (see Table 1).

View Article: PubMed Central

ABSTRACT

The blood-brain barrier (BBB) poses a unique challenge for drug delivery to the central nervous system (CNS). The BBB consists of a continuous layer of specialized endothelial cells linked together by tight junctions, pericytes, nonfenestrated basal lamina, and astrocytic foot processes. This complex barrier controls and limits the systemic delivery of therapeutics to the CNS. Several innovative strategies have been explored to enhance the transport of therapeutics across the BBB, each with individual advantages and disadvantages. Ongoing advances in delivery approaches that overcome the BBB are enabling more effective therapies for CNS diseases. In this review, we discuss: (1) the physiological properties of the BBB, (2) conventional strategies to enhance paracellular and transcellular transport through the BBB, (3) emerging concepts to overcome the BBB, and (4) alternative CNS drug delivery strategies that bypass the BBB entirely. Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS.

No MeSH data available.