Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

Xu, Leyuan; Zhang, Hao; Wu, Yue

doi:10.1021/cn400182z

Cited by 146 publications

(104 citation statements)

References 127 publications

(244 reference statements)

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“…PAMAM dendrimers bearing amines at the surface are appealing vectors because they not only possess inherent functions for gene delivery [26,27] but offer controlled nanoscale building blocks for construction of defined delivery systems with multifunctionality [28,29]. Although high generation polycaFolic acid-decorated polyamidoamine dendrimer mediates selective uptake and high expression of genes in head and neck cancer cells tionic PAMAM dendrimers tend to be more efficient in gene delivery, their generation-dependent toxicity is more prominent and surface functionalization is needed to maintain cytocompatibility and buffering capacity.…”

mentioning

confidence: 99%

Folic Acid-Decorated Polyamidoamine Dendrimer Mediates Selective Uptake and High Expression of Genes in Head and Neck Cancer Cells

Kittrell

Yeudall

2016

Nanomedicine (Lond.)

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Aim: Folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) was synthesized and studied for targeted delivery of genes to head and neck cancer cells expressing high levels of folate receptors (FRs). Methods: Cellular uptake, targeting specificity, cytocompatibility and transfection efficiency were evaluated. Results: G4-FA competes with free FA for the same binding site. G4-FA facilitates the cellular uptake of DNA plasmids in a FR-dependent manner and selectively delivers plasmids to FR-high cells, leading to enhanced gene expression. Conclusion: G4-FA is a suitable vector to deliver genes selectively to head and neck cancer cells. The fundamental understandings of G4-FA as a vector and its encouraging transfection results for head and neck cancer cells provided support for its further testing in vivo.

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confidence: 99%

Folic Acid-Decorated Polyamidoamine Dendrimer Mediates Selective Uptake and High Expression of Genes in Head and Neck Cancer Cells

Kittrell

Yeudall

2016

Nanomedicine (Lond.)

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“…The functionalization of PAMAMs (G4-G12 PAMAM) dramatically reduces diffusion in the CNS and dendrimer penetration in living neurons [48]. Moreover, the PEGylation of dendrimers results in improved biocompatibility, reduced immunogenicity, increased water solubility, prolonged half-life and increased protection against nuclease, thus protecting siRNA cargo from degradation [60].…”

Section: Dendrimersmentioning

confidence: 99%

Nanoparticles for Brain-Specific Drug and Genetic Material delivery, Imaging and Diagnosis

Posadas

Monteagudo

Ceña

2016

Nanomedicine (Lond.)

108

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The poor access of therapeutic drugs and genetic material into the central nervous system due to the presence of the blood-brain barrier often limits the development of effective noninvasive treatments and diagnoses of neurological disorders. Moreover, the delivery of genetic material into neuronal cells remains a challenge because of the intrinsic difficulty in transfecting this cell type. Nanotechnology has arisen as a promising tool to provide solutions for this problem. This review will cover the different approaches that have been developed to deliver drugs and genetic material efficiently to the central nervous system as well as the main nanomaterials used to image the central nervous system and diagnose its disorders.

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“…In the last few years, although numerous drug delivery carriers that can transport AEDs to the brain have been developed, including polymeric nanoparticles [5], polymeric micelles [6], and dendrimers [7], few of these carriers have advanced based on the pathological characteristics of epileptic seizures. We previously designed electroresponsive hydrogel nanoparticles (ERHNP) based on the abnormal electrical activity characteristics of epileptic seizures, and further modified ERHNP with the brain-targeting angiopep-2 peptide (ANG), a ligand of the low-density lipoprotein receptor-related protein, to improve penetration of the BBB [8].…”

Section: Introductionmentioning

confidence: 99%

Electroresponsive Nanoparticles Improve Antiseizure Effect of Phenytoin in Generalized Tonic-Clonic Seizures

et al. 2016

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Previously, we developed electroresponsive hydrogel nanoparticles (ERHNPs) modified with angiopep-2 (ANG) to facilitate the delivery of the antiseizure drug phenytoin sodium (PHT). However, the electroresponsive characteristics were not verified directly in epileptic mice and the optimal preparation formula for electroresponsive ability is still unclear. Here, we further synthesized PHT-loaded ANG-ERHNPs (ANG-PHT-HNPs) and PHT-loaded nonelectroresponsive hydrogel nanoparticles (ANG-PHTHNPs) by changing the content of sodium 4-vinylbenzene sulfonate in the preparation formulae. In vivo microdialysis analysis showed that ANG-PHT-ERHNPs not only have the characteristics of a higher distribution in the central nervous system, but also have electroresponsive ability, which resulted in a strong release of nonprotein-bound PHT during seizures.In both electrical-(maximal electrical shock) and chemicalinduced (pentylenetetrazole and pilocarpine) seizure models, ANG-PHT-ERHNPs lowered the effective therapeutic doses of PHT and demonstrated the improved antiseizure effects compared with ANG-PHT-HNPs or PHT solution. These results demonstrate that ANG-ERHNPs are able to transport PHT into the brain efficiently and release them when epileptiform activity occurred, which is due to the content of sodium 4-vinylbenzene sulfonate in formula. This may change the therapeutic paradigm of existing drug treatment for epilepsy into a type of on-demand control for epilepsy in the future.

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Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

Cited by 146 publications

References 127 publications

Folic Acid-Decorated Polyamidoamine Dendrimer Mediates Selective Uptake and High Expression of Genes in Head and Neck Cancer Cells

Folic Acid-Decorated Polyamidoamine Dendrimer Mediates Selective Uptake and High Expression of Genes in Head and Neck Cancer Cells

Nanoparticles for Brain-Specific Drug and Genetic Material delivery, Imaging and Diagnosis

Electroresponsive Nanoparticles Improve Antiseizure Effect of Phenytoin in Generalized Tonic-Clonic Seizures

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