Nanocarriers for spleen targeting: anatomo-physiological considerations, formulation strategies and therapeutic potential

Jindal, Anil

doi:10.1007/s13346-016-0304-0

Cited by 29 publications

(18 citation statements)

References 102 publications

(114 reference statements)

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“…Tumor endothelial cells (TECs) are genetically more stable than tumor cells (TCs) and this decreases the resistance to chemotherapeutic drugs. 19) In addition, TECs represent only a small fraction of the tumor, which decreases the dose of drugs needed compared with delivery to TCs. Unfortunately, there is no specific affinity of drugs and NPs for endothelial cells.…”

Section: Lnps For Gene Delivery To Endothelial Cellsmentioning

confidence: 99%

“…Generally, systemically administered LNPs carrying nucleic acids can access organs in which the capillaries are characterized by the presence of pores or fenestrations such as the liver and spleen. [17][18][19] Parenchymal cells in these two organs are thus considered accessible to LNPs, which make them particularly interesting candidate organs for gene therapy. The liver has received the most attention so far, and several lipid formulations are in different clinical trial stages.…”

Section: Introductionmentioning

confidence: 99%

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Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Khalil

Younis

Kimura

et al. 2020

Biological & Pharmaceutical Bulletin

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The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of lipid-based gene vectors. These efforts depend on the appropriate design of nanocarriers as well as the development of new lipids with improved gene delivery ability. Several ionizable lipids have recently been developed and have shown dramatically improved efficiency. However, enhancing the ability of nanocarriers to target specific cells in the body remains the most difficult challenge. Systemically administered LNPs can access organs in which the capillaries are characterized by the presence of fenestrations, such as the liver and spleen. The liver has received the most attention to date, although targeted delivery to the spleen has recently emerged as a promising tool for modulating the immune system. In this review, we discuss recent advances in the use of LNPs for cellspecific targeted delivery of nucleic acids. We focus mainly on targeting liver hepatocytes and spleen immune cells as excellent targets for gene therapy. We also discuss the potential of endothelial cells as an alternate approach for targeting organs with a continuous endothelium.

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Section: Lnps For Gene Delivery To Endothelial Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Khalil

Younis

Kimura

et al. 2020

Biological & Pharmaceutical Bulletin

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“…Indeed, it has been reported that the spleen receives barely 15% of the i.v. injected dose of nanomedicines [83]. Therefore, additional surface modification strategies may be needed for applications that require splenic accumulation of PLGA particles.…”

Section: Resultsmentioning

confidence: 99%

Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

et al. 2019

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Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm, and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

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“…Nevertheless,the successful protein and mRNAd elivery to the lung or spleen opens up awide range of possibilities for novel treatments of diseases. [28] Theu nderlying mechanisms are not clear at this stage.W eenvision that further structure-activity relationship studies on how LNPs interact with biological systems can shed some light on this issue.…”

Section: Angewandte Chemiementioning

confidence: 98%

Protein and mRNA Delivery Enabled by Cholesteryl‐Based Biodegradable Lipidoid Nanoparticles

Jarvis

Zhu

et al. 2020

Angew Chem Int Ed

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Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long‐standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl‐based disulfide bond‐containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).

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Nanocarriers for spleen targeting: anatomo-physiological considerations, formulation strategies and therapeutic potential

Cited by 29 publications

References 102 publications

Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

Protein and mRNA Delivery Enabled by Cholesteryl‐Based Biodegradable Lipidoid Nanoparticles

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