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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.


Distribution of gadolinium-labeled anionic liposomes following CED. (A) 3D axial T1-weighted gradient echo scans demonstrate the gadolinium in the nanocomplexes. (B) The data was reconstructed to provide a 3D model of the liposome distribution following CED into the striatum (green) and corpus callosum (purple). (C) Fluorescence microscopy was performed to visualize the anionic liposome distribution in the striatum (left) and corpus callosum (right) by using the incorporated rhodamine label. Scale bars = 500 µm. Modified with permission from Kenny et al. [236].
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Figure 3: Distribution of gadolinium-labeled anionic liposomes following CED. (A) 3D axial T1-weighted gradient echo scans demonstrate the gadolinium in the nanocomplexes. (B) The data was reconstructed to provide a 3D model of the liposome distribution following CED into the striatum (green) and corpus callosum (purple). (C) Fluorescence microscopy was performed to visualize the anionic liposome distribution in the striatum (left) and corpus callosum (right) by using the incorporated rhodamine label. Scale bars = 500 µm. Modified with permission from Kenny et al. [236].

Mentions: A wide variety of agents may be delivered via CED. These range from small molecule chemotherapeutic agents [222-224] and imaging tracers [225-227] to larger compounds such as proteins [228], viruses [229, 230], and nanoparticles [231-236] (see Fig. 3). Unlike diffusion, bulk flow typically distributes compounds homogenously regardless of molecular weight; nevertheless, larger molecules are still restricted by the size limitations of the extracellular space (ECS) of the brain. While early reports suggested that the ECS consists of pores that are 38-64 nm in width [237], more recent evidence suggests that the average pore size is actually closer to 100 nm, but that surface characteristics also play an important role in distribution throughout the brain [229, 238].


Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier
Distribution of gadolinium-labeled anionic liposomes following CED. (A) 3D axial T1-weighted gradient echo scans demonstrate the gadolinium in the nanocomplexes. (B) The data was reconstructed to provide a 3D model of the liposome distribution following CED into the striatum (green) and corpus callosum (purple). (C) Fluorescence microscopy was performed to visualize the anionic liposome distribution in the striatum (left) and corpus callosum (right) by using the incorporated rhodamine label. Scale bars = 500 µm. Modified with permission from Kenny et al. [236].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Distribution of gadolinium-labeled anionic liposomes following CED. (A) 3D axial T1-weighted gradient echo scans demonstrate the gadolinium in the nanocomplexes. (B) The data was reconstructed to provide a 3D model of the liposome distribution following CED into the striatum (green) and corpus callosum (purple). (C) Fluorescence microscopy was performed to visualize the anionic liposome distribution in the striatum (left) and corpus callosum (right) by using the incorporated rhodamine label. Scale bars = 500 µm. Modified with permission from Kenny et al. [236].
Mentions: A wide variety of agents may be delivered via CED. These range from small molecule chemotherapeutic agents [222-224] and imaging tracers [225-227] to larger compounds such as proteins [228], viruses [229, 230], and nanoparticles [231-236] (see Fig. 3). Unlike diffusion, bulk flow typically distributes compounds homogenously regardless of molecular weight; nevertheless, larger molecules are still restricted by the size limitations of the extracellular space (ECS) of the brain. While early reports suggested that the ECS consists of pores that are 38-64 nm in width [237], more recent evidence suggests that the average pore size is actually closer to 100 nm, but that surface characteristics also play an important role in distribution throughout the brain [229, 238].

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.