scholarly journals Modular Lipid Nanoparticle Platform Technology for siRNA and Lipophilic Prodrug Delivery

Small ◽  
2021 ◽  
pp. 2103025
Author(s):  
Roy Meel ◽  
Sam Chen ◽  
Josh Zaifman ◽  
Jayesh A. Kulkarni ◽  
Xu Ran S. Zhang ◽  
...  
Keyword(s):  
Lipid Nanoparticle ◽  
Lipophilic Prodrug ◽  
Platform Technology

scholarly journals Modular lipid nanoparticle platform technology for siRNA and lipophilic prodrug delivery

2020 ◽  
Author(s):  
Roy van der Meel ◽  
Sam Chen ◽  
Josh Zaifman ◽  
Jayesh A. Kulkarni ◽  
Xu Ran S. Zhang ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Gene Silencing ◽  
Building Blocks ◽  
Therapeutic Effects ◽  
Cancer Driver ◽  
Lipophilic Prodrug ◽  
Platform Technology ◽  
Modular Platform ◽  
Interfering Rna

ABSTRACTSuccessfully employing therapeutic nucleic acids, such as small interfering RNA (siRNA), requires chemical modifications or the use of nanocarrier technology to prevent their degradation in the circulation and to facilitate intracellular delivery. Lipid nanoparticles (LNP) are among the most advanced nanocarriers culminating in the first siRNA therapeutic’s clinical translation and approval. At the same time, their applicability as modular platform technology due to the interchangeable building blocks and siRNA payload hallmarks one of LNPs’ major advantages. In addition, drug derivatization approaches to synthesize lipophilic small molecule prodrugs enable stable incorporation in LNPs. This provides ample opportunities to develop combination therapies by co-encapsulating multiple therapeutic agents in a single formulation. Here, we describe how the modular LNP platform can be applied for combined gene silencing and chemotherapy to induce additive anti-cancer effects. We show that various lipophilic taxane prodrug derivatives and siRNA against the androgen receptor, a prostate cancer driver, can be efficiently and stably co-encapsulated in LNPs. In addition, we demonstrate that prodrug incorporation does not affect LNPs’ gene silencing ability and that the combination therapy induces additive therapeutic effects in vitro. Using a double-radiolabeling approach, we quantitively determined the LNPs’ and prodrugs’ pharmacokinetic properties and biodistribution following systemic administration in tumor-bearing mice. Our results indicate that co-encapsulation of siRNA and lipophilic prodrugs into LNPs is an attractive and straightforward approach for combination therapy development.GRAPHICAL ABSTRACT

Formulation Development of Tamoxifen Loaded Lipid Nanoparticle by Taguchi (L12 (2 11)) Orthogonal Array Design

2020 ◽  
Vol 16 ◽  
Author(s):  
Poovi Ganesan ◽  
N Damodharan
Keyword(s):  
Orthogonal Array ◽  
Drug Loading ◽  
Optimization Technique ◽  
Pharmaceutical Products ◽  
Water Soluble ◽  
Nanostructured Lipid Carrier ◽  
Orthogonal Array Design ◽  
Formulation Development ◽  
Array Design ◽  
Lipid Nanoparticle

Background: A better understanding of the biopharmaceutical and physicochemical properties of drugs and the pharmaco-technical factors would be of great help for developing pharmaceutical products. But, it is extremely difficult to study the effect of each variable and interaction among them through the conventional approach Objective: To screen the most influential factors affecting the particle size (PS) of lipid nanoparticle (LNPs) (solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC)) for poorly water-soluble BCS class-II drug like tamoxifen (TMX) to improve its oral bioavailability and to reduce its toxicity to tolerable limits using Taguchi (L12 (2 11)) orthogonal array design by applying computer optimization technique. Results: The size of all LNPs formulations prepared as per the experimental design varied between 172 nm and 3880 μm, polydispersity index between 0.033 and 1.00, encapsulation efficiency between 70.8% and 75.7%, and drug loading between 5.84% and 9.68%. The study showed spherical and non-spherical as well as aggregated and non-aggregated LNPs. Besides, it showed no interaction and amorphous form of the drug in LNPs formulation. The Blank NLCs exhibited no cytotoxicity on MCF-7 cells as compared to TMX solution, SLNs (F5) and NLCs (F12) suggests that the cause of cell death is primarily from the effect of TMX present in NLCs. Conclusions: The screening study clearly showed the importance of different individual factors significant effect for the LNPs formulation development and its overall performance in an in-vitro study with minimum experimentation thus saving considerable time, efforts, and resources for further in-depth study.

scholarly journals Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection

Nano Letters ◽  
2021 ◽  
Author(s):  
Uri Elia ◽  
Shahar Rotem ◽  
Erez Bar-Haim ◽  
Srinivas Ramishetti ◽  
Gonna Somu Naidu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Lipid Nanoparticle

scholarly journals Future considerations for the mRNA-lipid nanoparticle vaccine platform

2021 ◽  
Vol 48 ◽  
pp. 65-72
Author(s):  
Botond Z Igyártó ◽  
Sonya Jacobsen ◽  
Sonia Ndeupen
Keyword(s):  
Vaccine Platform ◽  
Lipid Nanoparticle

Acidic pH-induced changes in lipid nanoparticle membrane packing

2021 ◽  
Vol 1863 (8) ◽  
pp. 183627
Author(s):  
Kyoka Koitabashi ◽  
Hiroki Nagumo ◽  
Mizuka Nakao ◽  
Tomoko Machida ◽  
Kohki Yoshida ◽  
...  
Keyword(s):  
Acidic Ph ◽  
Lipid Nanoparticle ◽  
Induced Changes

scholarly journals Inflammatory Lesions: Cyclic Arginine–Glycine–Aspartate‐Decorated Lipid Nanoparticle Targeting toward Inflammatory Lesions Involves Hitchhiking with Phagocytes (Adv. Sci. 13/2021)

2021 ◽  
Vol 8 (13) ◽  
pp. 2170077
Author(s):  
Alexandros Marios Sofias ◽  
Geir Bjørkøy ◽  
Jordi Ochando ◽  
Linda Sønstevold ◽  
Maria Hegvik ◽  
...  
Keyword(s):  
Inflammatory Lesions ◽  
Lipid Nanoparticle

scholarly journals Protein L—More Than Just an Affinity Ligand

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 874
Author(s):  
Stefan Kittler ◽  
Mihail Besleaga ◽  
Julian Ebner ◽  
Oliver Spadiut
Keyword(s):  
Antibody Fragments ◽  
Downstream Process ◽  
Affinity Ligands ◽  
The Past ◽  
Affinity Ligand ◽  
Recombinant Production ◽  
Production Processes ◽  
Monitoring Tools ◽  
Platform Technology ◽  
Analytical Tools

In the past 30 years, highly specific drugs, known as antibodies, have conquered the biopharmaceutical market. In addition to monoclonal antibodies (mAbs), antibody fragments are successfully applied. However, recombinant production faces challenges. Process analytical tools for monitoring and controlling production processes are scarce and time-intensive. In the downstream process (DSP), affinity ligands are established as the primary and most important step, while the application of other methods is challenging. The use of these affinity ligands as monitoring tools would enable a platform technology to monitor process steps in the USP and DSP. In this review, we highlight the current applications of affinity ligands (proteins A, G, and L) and discuss further applications as process analytical tools.

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