In vitro screening of nanomedicines through the blood brain barrier: A critical review

Aparicio-Blanco, Juan; Martín-Sabroso, Cristina; Torres-Suárez, Ana Isabel

doi:10.1016/j.biomaterials.2016.06.051

Cited by 52 publications

(36 citation statements)

References 368 publications

(304 reference statements)

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“…However, further clinical studies of brain-targeted nanomedicines are warranted in the future, with increasing incidences of CNS cancers, many of whom being terrible rapidly progressing and so far untreatable tumors. Hence, the accumulation of data about the CNS physiology and about relevant receptors, the widening therapeutic armamentarium of drugs potentially useful in CNS chemotherapy, the alternative routes for administration and the estimation of the brain permeability with in vitro BBB models to early triage the potential of nanomedicines for optimum therapy of brain tumors envisage nanomedicines as a forthcoming routine approach [114].…”

Section: Discussionmentioning

confidence: 99%

Managing CNS Tumors: The Nanomedicine Approach

Aparicio-Blanco¹,

Torres-Suárez²

2017

New Approaches to the Management of Primary and Secondary CNS Tumors

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Albeit the rapidly evolving knowledge about tumor biochemistry enables various new drug molecules to be designed as treatments, malignant central nervous system (CNS) tumors remain untreatable due to the failure to expose the entire tumor to such therapeutics at pharmacologically meaningful quantities. Therefore, drug delivery in CNS tumors must be properly addressed, as otherwise, novel therapies will continue to fail. In this regard, nanomedicine poses an appealing platform for efficient drug delivery to the CNS, since it may be targeted to improve the drug availability in the site of action, which would be translated into lower drug doses and fewer side effects. Hence, the accumulation of data about the CNS physiology and their relevant receptors, the widening therapeutic armamentarium of drugs potentially useful in CNS chemotherapy and the alternative routes for administration may envisage nanomedicines as a forthcoming routine approach. Indeed, on the basis of the promising results gathered from preclinical studies of nanomedicine-based therapy both systemically and locally administered, some nanomedicines have already been approved for clinical trials in a variety of CNS tumor conditions to serve as the first steps in the translation of nanotherapy to clinic. Their outcome will steer research directions for further improvements.

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Section: Discussionmentioning

confidence: 99%

Managing CNS Tumors: The Nanomedicine Approach

Aparicio-Blanco¹,

Torres-Suárez²

2017

New Approaches to the Management of Primary and Secondary CNS Tumors

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“…Described as the “bottleneck in brain drug development,” the BBB consists of brain endothelium held together by tight junctions that forms a barrier around the brain with highly selective permeability [135]. In addition to the endothelial cells, other participating cells lend even more regulation to this barrier, including astrocytes, pericytes, microglia, and the vascular basement membrane [132]. For example, astrocytes surround the BBB with their end-feet, secreting factors that upregulate tight junction proteins and express key enzymes and transporters that contribute to the proper functioning of the barrier [132].…”

Section: Covalent Nanodelivery Systems For Imaging and Treatment Omentioning

confidence: 99%

“…In addition to the endothelial cells, other participating cells lend even more regulation to this barrier, including astrocytes, pericytes, microglia, and the vascular basement membrane [132]. For example, astrocytes surround the BBB with their end-feet, secreting factors that upregulate tight junction proteins and express key enzymes and transporters that contribute to the proper functioning of the barrier [132]. Microglial cells are an important part of brain’s immune defense system, and they are promptly activated and able to swallow pathogens and present antigens for T cell activation when the foreign entities pass through BBB and invade brain environment [136].…”

Section: Covalent Nanodelivery Systems For Imaging and Treatment Omentioning

confidence: 99%

Covalent nano delivery systems for selective imaging and treatment of brain tumors

Ljubimova

Sun

Mashouf

et al. 2017

Advanced Drug Delivery Reviews

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Nanomedicine is a rapidly evolving form of therapy that holds a great promise in superior drug delivery efficiency and therapeutic efficacy than conventional cancer treatment. In this review, we attempt to cover the benefits and the limitations of current nanomedicines with special attention to covalent nanoconjugates for imaging and drug delivery in brain. The improvement in brain tumor treatment remains dismal despite decades of efforts in drug development and patient care. One of the major obstacles in brain cancer treatment is the poor drug delivery efficiency owing to the unique blood-brain-barrier (BBB) in the CNS. Although various anti-cancer agents are available to treat tumors outside of the CNS, the majority fails to cross the BBB. In this regard, nanomedicines have increasingly drawn attention due to their multi-functionality and versatility. Nano-drugs can penetrate BBB and other biological barriers, and selectively accumulate in tumor cells, while concurrently decreasing systemic toxicity.

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“…[14][15][16][17][18][19] One significant challenge in Aβ imaging using NP contrast agents is the blood brain barrier (BBB), which has tight junctions between endothelial cells lining the blood vessels in the brain [20,21] and severely limits entries of macromolecules such as NPs into brains. [20,22] In order to overcome this, a common approach is to add mannitol into the NP formulation, which transiently opens up the BBB, allowing particles to diffuse into brain tissues. [23,24] However, it is challenging to apply this approach to humans due to the concern for possible brain infections with the opened BBB.…”

mentioning

confidence: 99%

Detection of β‐Amyloid by Sialic Acid Coated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer's Disease

Nasr

Kouyoumdjian

Mallett

et al. 2017

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The accumulation and formation of β-amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβ highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aβ binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP-BSA -Sia) to overcome the challenges in Aβ imaging in vivo. The NP-BSA -Sia is biocompatible with high magnetic relaxivities, suggesting that they are suitable contrast agents for magnetic resonance imaging (MRI). The NP-BSA -Sia binds with Aβ in a sialic acid dependent manner with high selectivities toward Aβ deposited on brains and cross the BBB in an in vitro model. The abilities of these NPs to detect Aβ in vivo in human AD transgenic mice by MRI are evaluated without the need to coinject mannitol to increase BBB permeability. T *-weighted MRI shows that Aβ plaques in mouse brains can be detected as aided by NP-BSA -Sia, which is confirmed by histological analysis. Thus, NP-BSA -Sia is a promising new tool for noninvasive in vivo detection of Aβ plaques.

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In vitro screening of nanomedicines through the blood brain barrier: A critical review

Cited by 52 publications

References 368 publications

Managing CNS Tumors: The Nanomedicine Approach

Managing CNS Tumors: The Nanomedicine Approach

Covalent nano delivery systems for selective imaging and treatment of brain tumors

Detection of β‐Amyloid by Sialic Acid Coated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer's Disease

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