scholarly journals Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Kathryn A. Whitehead ◽  
J. Robert Dorkin ◽  
Arturo J. Vegas ◽  
Philip H. Chang ◽  
Omid Veiseh ◽  
...  
Keyword(s):  
Sirna Delivery ◽  
Lipid Nanoparticles

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

RSC Advances ◽  
2017 ◽  
Vol 7 (15) ◽  
pp. 8823-8831 ◽  
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.

Targeted Liposomes for siRNA Delivery to Cancer

2018 ◽  
Vol 24 (23) ◽  
pp. 2664-2672 ◽  
Author(s):  
Josimar O. Eloy ◽  
Raquel Petrilli ◽  
Giovanni Loureiro Raspantini ◽  
Robert J. Lee
Keyword(s):  
Cancer Cells ◽  
Sirna Delivery ◽  
Growth Control ◽  
Lipid Nanoparticles ◽  
Drug Uptake ◽  
Cell Uptake ◽  
Reduced Toxicity ◽  
Interfering Rna

Background: RNA interference is a promising therapeutic tool for the treatment of a variety of diseases, with great potential for cancer therapy. Small interfering RNA (siRNA), however, presents several drawbacks that hamper its therapeutic application. Lipid nanoparticles, including liposomes, are delivery systems with great potential for siRNA delivery, protecting it from degradation, enhancing its cell uptake with the ability of controlled release. However, non-specific delivery and side effects could potentially limit the in vivo application. Therefore, targeting lipid nanoparticles to overexpressed receptors of cancer cells represents a strategy for better therapeutic outcome, with improved efficacy and reduced toxicity. For this purpose, lipid nanoparticles could be functionalized with several moieties that can be recognized by cancer cells more than by normal cells. These ligands include folate, transferrin, peptides, oligosaccharides, monoclonal antibodies and aptamers. Methods: In this paper, we reviewed functionalization strategies and addressed the major in vitro and in vivo findings in the field of cancer treatment with siRNA. Results: Many papers showed enhanced siRNA delivery by targeted liposomes, resulting in enhanced drug uptake and better cytotoxicity, with consequent better tumor growth control in xenograft studies. Conclusion: siRNA delivery mediated by functionalized liposomes is promising, but clinical trials need to be conducted.

Pharmacokinetic Evaluation of 99mTc-radiolabeled Solid Lipid Nanoparticles and Chitosan Coated Solid Lipid Nanoparticles

2020 ◽  
Vol 20 (13) ◽  
pp. 1044-1052
Author(s):  
Nasrin Abbasi Gharibkandi ◽  
Sajjad Molavipordanjani ◽  
Jafar Akbari ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Lipid Nanoparticles ◽  
High Resistivity ◽  
Scanning Calorimetry ◽  
Liver Uptake ◽  
Solid Lipid ◽  
Transmission Electron ◽  
Main Portion ◽  
Pharmacokinetic Behavior

Background: Solid Lipid Nanoparticles (SLNs) possess unique in vivo features such as high resistivity, bioavailability, and habitation at the target site. Coating nanoparticles with polymers such as chitosan greatly affects their pharmacokinetic behavior, stability, tissue uptake, and controlled drug delivery. The aim of this study was to prepare and evaluate the biodistribution of 99mTc-labeled SLNs and chitosan modified SLNs in mice. Methods: 99mTc-oxine was prepared and utilized to radiolabel pre-papered SLNs or chitosan coated SLNs. After purification of radiolabeled SLNs (99mTc-SLNs) and radiolabeled chitosan-coated SLNs (99mTc-Chi-SLNs) using Amicon filter, they were injected into BALB/c mice to evaluate their biodistribution patterns. In addition, nanoparticles were characterized using Transmission Electron Microscopy (TEM), Fourier-transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRD) and Dynamic Light Scattering (DLS). Results: 99mTc-oxine with high radiochemical purity (RCP~100%) and stability (RCP > 97% at 24 h) was used to provide 99mTc-SLNs and 99mTc-Chi-SLNs with high initial RCP (100%). TEM image and DLS data suggest 99mTc- SLNs susceptibility to aggregation. To that end, the main portion of 99mTc-SLNs radioactivity accumulates in the liver and intestines, while 99mTc-Chi-SLNs sequesters in the liver, intestines and kidneys. The blood radioactivity of 99mTc-Chi-SLNs was higher than that of 99mTc-SLNs by 7.5, 3.17 and 3.5 folds at 1, 4 and 8 h post-injection. 99mTc- Chi-SLNs uptake in the kidneys in comparison with 99mTc-SLNs was higher by 37.48, 5.84 and 11 folds at 1, 4 and 8h. Conclusion: The chitosan layer on the surface of 99mTc-Chi-SLNs reduces lipophilicity in comparison with 99mTc- SLNs. Therefore, 99mTc-Chi-SLNs are less susceptible to aggregation, which leads to their lower liver uptake and higher kidney uptake and blood concentration.

In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

2019 ◽  
Vol 20 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chi Zhang ◽  
Zhichun Gu ◽  
Long Shen ◽  
Xianyan Liu ◽  
Houwen Lin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Outcome ◽  
Neuroprotective Effect ◽  
Sirna Delivery ◽  
Repeated Administration ◽  
Spatial Learning And Memory ◽  
In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

Solid Lipid Nanoparticles (SLNs) Gels for Topical Delivery of Aceclofenac in vitro and in vivo Evaluation

2013 ◽  
Vol 10 (6) ◽  
pp. 656-666 ◽  
Author(s):  
Sandipan Dasgupta ◽  
Surajit Ghosh ◽  
Subhabrata Ray ◽  
Bhaskar Mazumder
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Topical Delivery ◽  
Lipid Nanoparticles ◽  
In Vivo Evaluation ◽  
Solid Lipid

scholarly journals Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver

2021 ◽  
Vol 7 (9) ◽  
pp. eabf4398
Author(s):  
M. Kim ◽  
M. Jeong ◽  
S. Hur ◽  
Y. Cho ◽  
J. Park ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Targeted Delivery ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Nanoparticles ◽  
Liver Sinusoidal Endothelial Cells ◽  
Main Challenge ◽  
Cell Type Specific ◽  
Selective Delivery

Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here, we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and LSECs. The effects of particle size and polyethylene glycol–lipid content in the LNPs were evaluated for the hepatocyte-specific delivery of mRNA by ApoE-mediated cellular uptake through low-density lipoprotein receptors. Targeted delivery of RNA to LSECs was further investigated using active ligands. Incorporation of mannose allowed the selective delivery of RNA to LSECs, while minimizing the unwanted cellular uptake by hepatocytes. These results demonstrate that engineered LNPs have great potential for the cell type–specific delivery of RNA into the liver and other tissues.

scholarly journals Spatiotemporally programmable cascade hybridization of hairpin DNA in polymeric nanoframework for precise siRNA delivery

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Li ◽  
Wenting Yu ◽  
Jiaojiao Zhang ◽  
Yuhang Dong ◽  
Xiaohui Ding ◽  
...  
Keyword(s):  
Steric Effect ◽  
Sirna Delivery ◽  
Dna Nanotechnology ◽  
Hybridization Chain Reaction ◽  
Dna Nanostructures ◽  
Chain Reaction ◽  
Dna Hairpins ◽  
In Vivo Experiments ◽  
Dna And Rna

AbstractDNA nanostructures have been demonstrated as promising carriers for gene delivery. In the carrier design, spatiotemporally programmable assembly of DNA under nanoconfinement is important but has proven highly challenging due to the complexity–scalability–error of DNA. Herein, a DNA nanotechnology-based strategy via the cascade hybridization chain reaction (HCR) of DNA hairpins in polymeric nanoframework has been developed to achieve spatiotemporally programmable assembly of DNA under nanoconfinement for precise siRNA delivery. The nanoframework is prepared via precipitation polymerization with Acrydite-DNA as cross-linker. The potential energy stored in the loops of DNA hairpins can overcome the steric effect in the nanoframework, which can help initiate cascade HCR of DNA hairpins and achieve efficient siRNA loading. The designer tethering sequence between DNA and RNA guarantees a triphosadenine triggered siRNA release specifically in cellular cytoplasm. Nanoframework provides stability and ease of functionalization, which helps address the complexity–scalability–error of DNA. It is exemplified that the phenylboronate installation on nanoframework enhanced cellular uptake and smoothed the lysosomal escape. Cellular results show that the siRNA loaded nanoframework down-regulated the levels of relevant mRNA and protein. In vivo experiments show significant therapeutic efficacy of using siPLK1 loaded nanoframework to suppress tumor growth.

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