Mixing lipids to manipulate the ionization status of lipid nanoparticles for specific tissue targeting

Abstract Advantages of polymeric nanoparticles as drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, and surface ligands, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. This review seeks to discuss the available literature on the biodistribution of polymeric nanoparticles and discuss the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, with potential impact on clinical applications.

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Efficient in vivo siRNA delivery by stabilized d-peptide-based lipid nanoparticles

RSC Advances ◽

10.1039/c6ra25862j ◽

2017 ◽

Vol 7 (15) ◽

pp. 8823-8831 ◽

Cited By ~ 6

Author(s):

Tsogzolmaa Ganbold ◽

Gerile Gerile ◽

Hai Xiao ◽

Huricha Baigude

Keyword(s):

Sirna Delivery ◽

Lipid Nanoparticles ◽

Tissue Targeting ◽

Delivery Efficiency

A lipid functionalized d-dipeptide has shown remarkable biocompatibility and tissue targeting as well as excellent RNAi delivery efficiency in vivo.

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Hydrodynamic Delivery of Chitosan-Folate-DNA Nanoparticles in Rats with Adjuvant-Induced Arthritis

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/148763 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Qin Shi ◽

Huijie Wang ◽

Covi Tran ◽

Xingping Qiu ◽

Françoise M. Winnik ◽

...

Keyword(s):

Soleus Muscle ◽

Dna Nanoparticles ◽

Tissue Sections ◽

Adjuvant Induced Arthritis ◽

Tissue Targeting ◽

Specific Tissue ◽

The Right ◽

Hydrodynamic Delivery

50 kDa chitosan was conjugated with folate, a specific tissue-targeting ligand. Nanoparticles such as chitosan-DNA and folate-chitosan-DNA were prepared by coacervation process. The hydrodynamic intravenous injection of nanoparticles was performed in the right posterior paw in normal and arthritic rats. Our results demonstrated that the fluorescence intensity of DsRed detected was 5 to 12 times more in the right soleus muscle and in the right gastro muscle than other tissue sections. β-galactosidase gene expression with X-gal substrate and folate-chitosan-plasmid nanoparticles showed best coloration in the soleus muscle. Treated arthritic animals also showed a significant decrease in paw swelling and IL-1β and PGE2concentration in serum compared to untreated rats. This study demonstrated that a nonviral gene therapeutic approach using hydrodynamic delivery could help transfect more efficiently folate-chitosan-DNA nanoparticlesin vitro/in vivoand could decrease inflammation in arthritic rats.

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Genetic Screen in Adult Drosophila Reveals That dCBP Depletion in Glial Cells Mitigates Huntington Disease Pathology through a Foxo-Dependent Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22083884 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3884

Author(s):

Elodie Martin ◽

Raheleh Heidari ◽

Véronique Monnier ◽

Hervé Tricoire

Keyword(s):

Glial Cells ◽

Cell Types ◽

Cag Repeat ◽

Mutant Huntingtin ◽

Tissue Targeting ◽

Specific Tissue ◽

In Vivo Screen ◽

The Impact ◽

Dependent Pathway

Huntington’s disease (HD) is a progressive and fatal autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the first exon of the huntingtin gene (HTT). In spite of considerable efforts, there is currently no treatment to stop or delay the disease. Although HTT is expressed ubiquitously, most of our knowledge has been obtained on neurons. More recently, the impact of mutant huntingtin (mHTT) on other cell types, including glial cells, has received growing interest. It is currently unclear whether new pathological pathways could be identified in these cells compared to neurons. To address this question, we performed an in vivo screen for modifiers of mutant huntingtin (HTT-548-128Q) induced pathology in Drosophila adult glial cells and identified several putative therapeutic targets. Among them, we discovered that partial nej/dCBP depletion in these cells was protective, as revealed by strongly increased lifespan and restored locomotor activity. Thus, dCBP promotes the HD pathology in glial cells, in contrast to previous opposite findings in neurons. Further investigations implicated the transcriptional activator Foxo as a critical downstream player in this glial protective pathway. Our data suggest that combinatorial approaches combined to specific tissue targeting may be required to uncover efficient therapies in HD.

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Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features

Viruses ◽

10.3390/v13010101 ◽

2021 ◽

Vol 13 (1) ◽

pp. 101

Author(s):

Mario Mietzsch ◽

Ariana Jose ◽

Paul Chipman ◽

Nilakshee Bhattacharya ◽

Nadia Daneshparvar ◽

...

Keyword(s):

Three Dimensional ◽

Viral Proteins ◽

Binding Pocket ◽

Transduction Efficiency ◽

Adeno Associated Virus ◽

Cryo Electron Microscopy ◽

Loop Conformations ◽

Tissue Targeting ◽

Clade C ◽

Specific Tissue

The capsid structures of most Adeno-associated virus (AAV) serotypes, already assigned to an antigenic clade, have been previously determined. This study reports the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 determined by cryo-electron microscopy and three-dimensional image reconstruction to 2.96, 2.86, 2.54, and 2.76 Å resolution, respectively. These structures complete the structural atlas of the AAV serotype capsids. AAV7 represents the first clade D capsid structure; AAV11 and AAV12 are of a currently unassigned clade that would include AAV4; and AAV13 represents the first AAV2-AAV3 hybrid clade C capsid structure. These newly determined capsid structures all exhibit the AAV capsid features including 5-fold channels, 3-fold protrusions, 2-fold depressions, and a nucleotide binding pocket with an ordered nucleotide in genome-containing capsids. However, these structures have viral proteins that display clade-specific loop conformations. This structural characterization completes our three-dimensional library of the current AAV serotypes to provide an atlas of surface loop configurations compatible with capsid assembly and amenable for future vector engineering efforts. Derived vectors could improve gene delivery success with respect to specific tissue targeting, transduction efficiency, antigenicity or receptor retargeting.

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Extracellular-Matrix-Anchored Click Motifs for Specific Tissue Targeting

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.9b00589 ◽

2019 ◽

Author(s):

Mary R. Adams ◽

Christopher T. Moody ◽

Jennifer L. Sollinger ◽

Yevgeny Brudno

Keyword(s):

Extracellular Matrix ◽

Tissue Targeting ◽

Specific Tissue

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Selection and Preparation of Specific Tissue Regions For Tem Using Large Epoxy-Embedded Blocks

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010007206x ◽

1973 ◽

Vol 31 ◽

pp. 324-325 ◽

Cited By ~ 1

Author(s):

P. M. Lowrie ◽

W. S. Tyler

Keyword(s):

Electron Microscopy ◽

Anatomical Structures ◽

Ultrastructural Studies ◽

Transmission Electron ◽

Microscopic Evaluation ◽

Embedded Blocks ◽

Specific Tissue ◽

Definition Of ◽

Areas Of Interest ◽

Selection Of

The importance of examining stained 1 to 2μ plastic sections by light microscopy has long been recognized, both for increased definition of many histologic features and for selection of specimen samples to be used in ultrastructural studies. Selection of specimens with specific orien ation relative to anatomical structures becomes of critical importance in ultrastructural investigations of organs such as the lung. The uantity of blocks necessary to locate special areas of interest by random sampling is large, however, and the method is lacking in precision. Several methods have been described for selection of specific areas for electron microscopy using light microscopic evaluation of paraffin, epoxy-infiltrated, or epoxy-embedded large blocks from which thick sections were cut. Selected areas from these thick sections were subsequently removed and re-embedded or attached to blank precasted blocks and resectioned for transmission electron microscopy (TEM).

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