Multifunctional Nanoparticles for Successful Targeted Drug Delivery across the Blood-Brain Barrier

Vieira, Débora Braga; Gamarra, Lionel Fernel

doi:10.5772/intechopen.76922

Cited by 12 publications

(10 citation statements)

References 137 publications

(171 reference statements)

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“…Another interesting strategy to deliver drugs into the brain exploiting RMT is the use of nanoparticles (NPs) coupled with mAbs or peptides that recognize these receptors [43,56,57]. NPs are colloidal carriers of natural or synthetic origin with a size varying from 1 to 1000 nm.…”

Section: Physiological Approachmentioning

confidence: 99%

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

et al. 2020

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The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood–brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells.

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Section: Physiological Approachmentioning

confidence: 99%

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

et al. 2020

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“…These nanocages were further optimized for better magnetic properties with enhanced relaxivity of ferritin magnetic core (to be published). PEG coating on the MNS helps the nanoparticles stay longer inside the brain regions by avoiding the process of opsonization by macrophages and therefore, to elicit a lower immune response [24]. Silica coating as the outer layer provides increased biological stability to the SiNP and ease of surface modification to generate multiple functionalizations on the nanoparticles [21].…”

Section: Resultsmentioning

confidence: 99%

Conjugates of neuroprotective chaperone L-PGDS provide MRI contrast for detection of amyloid β-rich regions in live Alzheimer’s Disease mouse model brain

Sharma¹,

Grandjean²,

Phillips³

et al. 2020

Preprint

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Endogenous brain proteins can recognize the toxic oligomers of amyloid-β (Aβ) peptides implicated in Alzheimer's disease (AD) and interact with them to prevent their aggregation.Lipocalin-type Prostaglandin D Synthase (L-PGDS) is a major Aβ-chaperone protein in the human cerebrospinal fluid. Here we demonstrate that L-PGDS detects amyloids in diseased mouse brain. Conjugation of L-PGDS with magnetic nanoparticles enhanced the contrast for magnetic resonance imaging. We conjugated the L-PGDS protein with ferritin nanocages to detect amyloids in the AD mouse model brain. We show here that the conjugates administered through intraventricular injections co-localize with amyloids in the mouse brain.These conjugates can target the brain regions through non-invasive intranasal administration, as shown in healthy mice. These conjugates can inhibit the aggregation of amyloids in vitro and show potential neuroprotective function by breaking down the mature amyloid fibrils.

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“…Nanotechnology-based drug delivery systems are a powerful method for drug transport into the brain [40,51,52]. A well-known candidate for CNS targeted delivery of drugs is colloidal-based particulate systems [53][54][55]. NPs are used in the form of nanospheres as well as nanocapsules, and the drug is entrapped inside the matrix or attached to the surface [56,57].…”

Section: Nano-scale Drug Delivery To the Brainmentioning

confidence: 99%

Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics

et al. 2020

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The blood–brain barrier (BBB) acts as a barrier to prevent the central nervous system (CNS) from damage by substances that originate from the blood circulation. The BBB limits drug penetration into the brain and is one of the major clinical obstacles to the treatment of CNS diseases. Nanotechnology-based delivery systems have been tested for overcoming this barrier and releasing related drugs into the brain matrix. In this review, nanoparticles (NPs) from simple to developed delivery systems are discussed for the delivery of a drug to the brain. This review particularly focuses on polymeric nanomaterials that have been used for CNS treatment. Polymeric NPs such as polylactide (PLA), poly (D, L-lactide-co-glycolide) (PLGA), poly (ε-caprolactone) (PCL), poly (alkyl cyanoacrylate) (PACA), human serum albumin (HSA), gelatin, and chitosan are discussed in detail.

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Multifunctional Nanoparticles for Successful Targeted Drug Delivery across the Blood-Brain Barrier

Cited by 12 publications

References 137 publications

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

Conjugates of neuroprotective chaperone L-PGDS provide MRI contrast for detection of amyloid β-rich regions in live Alzheimer’s Disease mouse model brain

Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics

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