Intranasal delivery of hGDNF plasmid DNA nanoparticles results in long-term and widespread transfection of perivascular cells in rat brain

Aly, Amirah E-E; Harmon, Brendan Trevor; Padegimas, Linas; Sesenoglu-Laird, Ozge; Cooper, Mark J.; Yurek, David M.; Waszczak, Barbara L.

doi:10.1016/j.nano.2018.11.006

Cited by 25 publications

(21 citation statements)

References 37 publications

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“…Interestingly, the results obtained using tyrosine hydroxylase‐immumohistochemical staining indicated that intranasal pretreatment with GDNF plasmid before a 6‐hydroxydopmaine lesion resulted in the significant neuroprotection of dopamine cells of rats. Other studies have also provided evidence in support of GDNF gene therapy using non‐viral vectors being a non‐invasive and effective therapy approach for PD.…”

Section: Therapeutic Genes For Cns Diseasesmentioning

confidence: 96%

Non‐viral nucleic acid delivery to the central nervous system and brain tumors

Wang

Huang

2019

The Journal of Gene Medicine

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Gene therapy is a rapidly emerging remedial route for many serious incurable diseases, such as central nervous system (CNS) diseases. Currently, nucleic acid medicines, including DNAs encoding therapeutic or destructive proteins, small interfering RNAs or microRNAs, have been successfully delivered to the CNS with gene delivery vectors using various routes of administration and have subsequently exhibited remarkable therapeutic efficiency. Among these vectors, non‐viral vectors are favorable for delivering genes into the CNS as a result of their many special characteristics, such as low toxicity and pre‐existing immunogenicity, high gene loading efficiency and easy surface modification. In this review, we highlight the main types of therapeutic genes that have been applied in the therapy of CNS diseases and then outline non‐viral gene delivery vectors.

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Section: Therapeutic Genes For Cns Diseasesmentioning

confidence: 96%

Non‐viral nucleic acid delivery to the central nervous system and brain tumors

Wang

Huang

2019

The Journal of Gene Medicine

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“…Emerging physical strategies have been improved to ensure drug delivery across the BBB and tumor-BBB, this is a difficult event because barriers allow only the selective passage of small molecules. Docetaxel-conjugated nanoparticle delivery has been highlighted in pericytes from neuroblastoma rats [119] and a recent study has shown that the intranasal administration of plasmid DNA, encoding GDNF encapsulated within nanoparticles, was able to transfect perivascular cells, probably pericytes [120]. The delivery of drugs targeting pericytes carried by nanoparticles could provide novel therapeutic strategies for the treatment of many neurovascular diseases, including brain cancers.…”

Section: Pericyte-targeted Anti-tumor Therapymentioning

confidence: 99%

Pericytes in Microvessels: From “Mural” Function to Brain and Retina Regeneration

Caporarello

D’Angeli

Cambria

et al. 2019

IJMS

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Pericytes are branched cells located in the wall of capillary blood vessels that are found throughout the body, embedded within the microvascular basement membrane and wrapping endothelial cells, with which they establish a strong physical contact. Pericytes regulate angiogenesis, vessel stabilization, and contribute to the formation of both the blood-brain and blood-retina barriers by Angiopoietin-1/Tie-2, platelet derived growth factor (PDGF) and transforming growth factor (TGF) signaling pathways, regulating pericyte-endothelial cell communication. Human pericytes that have been cultured for a long period give rise to multilineage progenitor cells and exhibit mesenchymal stem cell (MSC) features. We focused our attention on the roles of pericytes in brain and ocular diseases. In particular, pericyte involvement in brain ischemia, brain tumors, diabetic retinopathy, and uveal melanoma is described. Several molecules, such as adenosine and nitric oxide, are responsible for pericyte shrinkage during ischemia-reperfusion. Anti-inflammatory molecules, such as IL-10, TGFβ, and MHC-II, which are increased in glioblastoma-activated pericytes, are responsible for tumor growth. As regards the eye, pericytes play a role not only in ocular vessel stabilization, but also as a stem cell niche that contributes to regenerative processes in diabetic retinopathy. Moreover, pericytes participate in melanoma cell extravasation and the genetic ablation of the PDGF receptor reduces the number of pericytes and aberrant tumor microvessel formation with important implications for therapy efficacy. Thanks to their MSC features, pericytes could be considered excellent candidates to promote nervous tissue repair and for regenerative medicine.

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“…Intranasal drug delivery, known as the nose-to-brain (N2B) route, is a noninvasive method to deliver agents of various sizes, including smallmolecule drugs, 109,110) proteins, 111,112) oligonucleotides, [113][114][115] or gene vectors. 116,117) N2B delivery of insulin was shown to improve memory impairment in AD patients. 118) Intranasally administered drugs reach the brain through two pathways, the olfactory pathway and trigeminal pathway.…”

Section: Nose-to-brain Drug Deliverymentioning

confidence: 99%

“…Belur et al demonstrated that N2B delivery of AAV9 exerted efficient gene expression in the olfactory bulb. 116) Furthermore, Aly et al succeeded in N2B gene delivery of plasmid DNA compacted by PEG-conjugated poly-L-lysine. 117) Transgene expression was observed in the perivascular region of the olfactory bulb and brainstem.…”

Section: Nose-to-brain Drug Deliverymentioning

confidence: 99%

Recent Strategies for Targeted Brain Drug Delivery

2020

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Because the brain is the most important human organ, many brain disorders can cause severe symptoms. For example, glioma, one type of brain tumor, is progressive and lethal, while neurodegenerative diseases cause severe disability. Nevertheless, medical treatment for brain diseases remains unsatisfactory, and therefore innovative therapies are desired. However, the development of therapies to treat some cerebral diseases is difficult because the blood-brain barrier (BBB) or blood-brain tumor barrier prevents drugs from entering the brain. Hence, drug delivery system (DDS) strategies are required to deliver therapeutic agents to the brain. Recently, brain-targeted DDS have been developed, which increases the quality of therapy for cerebral disorders. This review gives an overview of recent brain-targeting DDS strategies. First, it describes strategies to cross the BBB. This includes BBB-crossing ligand modification or temporal BBB permeabilization. Strategies to avoid the BBB using local administration are also summarized. Intrabrain drug distribution is a crucial factor that directly determines the therapeutic effect, and thus it is important to evaluate drug distribution using optimal methods. We introduce some methods for evaluating drug distribution in the brain. Finally, applications of brain-targeted DDS for the treatment of brain tumors, Alzheimer's disease, Parkinson's disease, and stroke are explained.

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Intranasal delivery of hGDNF plasmid DNA nanoparticles results in long-term and widespread transfection of perivascular cells in rat brain

Cited by 25 publications

References 37 publications

Non‐viral nucleic acid delivery to the central nervous system and brain tumors

Non‐viral nucleic acid delivery to the central nervous system and brain tumors

Pericytes in Microvessels: From “Mural” Function to Brain and Retina Regeneration

Recent Strategies for Targeted Brain Drug Delivery

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