Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform

10.3791/62226 ◽  
2021 ◽  
Author(s):  
Christina M. Bailey-Hytholt ◽  
Paroma Ghosh ◽  
Julia Dugas ◽  
Isidro E. Zarraga ◽  
Amey Bandekar
Keyword(s):  
Gene Delivery ◽  
Lipid Nanoparticles ◽  
Microfluidic Mixing

scholarly journals The Importance of Poly(ethylene glycol) and Lipid Structure in Targeted Gene Delivery to Lymph Nodes by Lipid Nanoparticles

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1068 ◽  
Author(s):  
Danijela Zukancic ◽  
Estelle J. A. Suys ◽  
Emily H. Pilkington ◽  
Azizah Algarni ◽  
Hareth Al-Wassiti ◽  
...  
Keyword(s):  
Lymph Node ◽  
Gene Delivery ◽  
Ethylene Glycol ◽  
Lymph Nodes ◽  
Injection Site ◽  
Targeted Delivery ◽  
Lipid Nanoparticles ◽  
Tween 20 ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene

Targeted delivery of nucleic acids to lymph nodes is critical for the development of effective vaccines and immunotherapies. However, it remains challenging to achieve selective lymph node delivery. Current gene delivery systems target mainly to the liver and typically exhibit off-target transfection at various tissues. Here we report novel lipid nanoparticles (LNPs) that can deliver plasmid DNA (pDNA) to a draining lymph node, thereby significantly enhancing transfection at this target organ, and substantially reducing gene expression at the intramuscular injection site (muscle). In particular, we discovered that LNPs stabilized by 3% Tween 20, a surfactant with a branched poly(ethylene glycol) (PEG) chain linking to a short lipid tail, achieved highly specific transfection at the lymph node. This was in contrast to conventional LNPs stabilized with a linear PEG chain and two saturated lipid tails (PEG-DSPE) that predominately transfected at the injection site (muscle). Interestingly, replacing Tween 20 with Tween 80, which has a longer unsaturated lipid tail, led to a much lower transfection efficiency. Our work demonstrates the importance of PEGylation in selective organ targeting of nanoparticles, provides new insights into the structure–property relationship of LNPs, and offers a novel, simple, and practical PEGylation technology to prepare the next generation of safe and effective vaccines against viruses or tumours.

scholarly journals Development and characterization of an improved formulation of cholesteryl oleate-loaded cationic solid-lipid nanoparticles as an efficient non-viral gene delivery system

2019 ◽  
Vol 184 ◽  
pp. 110533 ◽  
Author(s):  
María J. Limeres ◽  
Marc Suñé-Pou ◽  
Silvia Prieto-Sánchez ◽  
Cristina Moreno-Castro ◽  
Alejandro D. Nusblat ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Solid Lipid Nanoparticles ◽  
Cholesteryl Oleate ◽  
Lipid Nanoparticles ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Solid Lipid ◽  
Viral Gene Delivery

The Effect of Size and Charge of Lipid Nanoparticles Prepared by Microfluidic Mixing on Their Lymph Node Transitivity and Distribution

2020 ◽  
Vol 17 (3) ◽  
pp. 944-953 ◽  
Author(s):  
Takashi Nakamura ◽  
Minori Kawai ◽  
Yusuke Sato ◽  
Masatoshi Maeki ◽  
Manabu Tokeshi ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lipid Nanoparticles ◽  
Microfluidic Mixing

scholarly journals Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core

2012 ◽  
Vol 116 (34) ◽  
pp. 18440-18450 ◽  
Author(s):  
Alex K. K. Leung ◽  
Ismail M. Hafez ◽  
Svetlana Baoukina ◽  
Nathan M. Belliveau ◽  
Igor V. Zhigaltsev ◽  
...  
Keyword(s):  
Lipid Nanoparticles ◽  
Microfluidic Mixing

scholarly journals Correction to “Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core”

2012 ◽  
Vol 116 (41) ◽  
pp. 22104-22104 ◽  
Author(s):  
Alex K. K. Leung ◽  
Ismail M. Hafez ◽  
Svetlana Baoukina ◽  
Nathan M. Belliveau ◽  
Igor V. Zhigaltsev ◽  
...  
Keyword(s):  
Lipid Nanoparticles ◽  
Microfluidic Mixing

scholarly journals Genospheres: self-assembling nucleic acid-lipid nanoparticles suitable for targeted gene delivery

Gene Therapy ◽  
2005 ◽  
Vol 13 (7) ◽  
pp. 646-651 ◽  
Author(s):  
M E Hayes ◽  
D C Drummond ◽  
D B Kirpotin ◽  
W W Zheng ◽  
C O Noble ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Gene Delivery ◽  
Lipid Nanoparticles ◽  
Targeted Gene Delivery ◽  
Self Assembling

scholarly journals Computational and Experimental Approaches to Investigate Lipid Nanoparticles as Drug and Gene Delivery Systems

2020 ◽  
Vol 20 ◽  
Author(s):  
Chun Chan ◽  
Shi Du ◽  
Yizhou Dong ◽  
Xiaolin Cheng
Keyword(s):  
Gene Delivery ◽  
Research And Development ◽  
Lipid Nanoparticles ◽  
Delivery Systems ◽  
Functional Information ◽  
Computational Approaches ◽  
The Us ◽  
Experimental Approaches ◽  
Reduced Toxicity ◽  
Drug And Gene Delivery

: Lipid nanoparticles (LNPs) have been widely applied for drug and gene delivery. More than twenty years ago, Doxil TM was the first LNPs-based drug approved by the US Food and Drug Administration (FDA). Since then, with decades of research and development, more and more LNP-based therapeutics have been used to treat diverse diseases, which often offer the benefits of reduced toxicity and/or enhanced efficacy compared to the active ingredients alone. Here, we provide a review on recent advances in the development of efficient and robust LNPs for drug/gene delivery. We emphasize the importance of rationally combining experimental and computational approaches, especially those providing multiscale structural and functional information of LNPs, to the design of novel and powerful LNP-based delivery systems.

scholarly journals A mini-review of Nanocarriers in drug delivery systems Nanocarriers in drug delivery systems

2021 ◽  
Author(s):  
Mahsa Mazdaei ◽  
Kofi Asare-Addo
Keyword(s):  
Drug Delivery ◽  
Gene Delivery ◽  
Cancer Chemotherapy ◽  
Solid Lipid Nanoparticles ◽  
Drug Delivery Systems ◽  
Lipid Nanoparticles ◽  
Delivery Systems ◽  
Therapeutic Gene ◽  
Solid Lipid ◽  
The Past

The application of nanotechnology indrug delivery systems (DDS) has been researched widely and seen an advancementover the past three decades. Since the 1970s, nanoparticles were primarilyutilised in vaccine deliveries and cancer chemotherapy. In more recent years,they have been found to hold promises for broader applications such as inproteins and therapeutic gene delivery systems. To date, there have been only ahandful of nanocarrier-loaded drugs commercialised into the pharmaceuticalmarket. More research is thus needed to facilitate a breakthrough of theseproducts into the current market. This mini-review mainly focuses on four typesof commonly utilised organic nanocarriers including micelles, compactpolymerics, solid-lipid nanoparticles and liposomal vesicles and discusses theprogress and some challenges associated with these nanoparticles (NP). 

A promising targeted gene delivery system: Folate-modified dexamethasone-conjugated solid lipid nanoparticles

2014 ◽  
Vol 52 (8) ◽  
pp. 1039-1044 ◽  
Author(s):  
Wei Wang ◽  
Fang Zhou ◽  
Linfu Ge ◽  
Ximin Liu ◽  
Fansheng Kong
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Solid Lipid Nanoparticles ◽  
Lipid Nanoparticles ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Solid Lipid
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