L-12：Lipid Nanoparticle Formulation Technology Exhibiting High Translocation and Accumulation in Pancreatic Islets and Exocrine Pancreatic Tissue

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＜L-12＞：Life Science, Pharmaceutical Sciences sdgs-03
 

Lipid Nanoparticle Formulation Technology Exhibiting High Translocation and Accumulation in Pancreatic Islets and Exocrine Pancreatic Tissue
― Development of a Delivery Platform for Pancreas-Targeted Therapeutics ―

Takanori Kanazawa Professor
Department of Clinical Pharmacology, Pharmaceutical Life Sciences, Pharmaceutical Sciences, Graduate School of Biomedical Sciences
Keywords Lipid nanoparticles (LNPs), drug delivery system (DDS), pancreas, pancreatic islets, diabetes, pancreatic β cells, pancreatic cancer
Laboratory URL https://www.tokushima-u.ac.jp/ph/faculty/labo/cpt/
Research Overview
● Drug Delivery to the Pancreas and Pancreatic Islets Is Essential for Fundamental Prevention and Treatment of Diabetes
Pancreatic islets, which contain insulin-producing β cells, are key target tissues for the fundamental prevention and treatment of diabetes. Existing pharmaceuticals, veterinary drugs, and functional health foods mainly provide symptomatic relief by suppressing glucose absorption and therefore cannot fundamentally address the progressive loss of pancreatic β cells.
The development of next-generation anti-diabetic therapies requires delivery of compounds that protect and promote the proliferation of pancreatic β cells to pancreatic islets tissues that are notoriously difficult to target. However, only a limited of  prior studies have been demonstrated efficient drug delivery to the pancreatic islets.

● Technical Challenge: Design of LNPs with Enhanced Accumulation in Pancreatic Islets; Optimization of Lipid Composition and Particle Size
Lipid nanoparticles (LNPs) are composed of helper lipids (neutral phospholipids and cholesterol), PEGylated lipids, and ionizable lipids, and are widely serve as drug delivery system (DDS) carriers for nucleic acids such as mRNA and siRNA.
In this study, we identified optimal lipid composition and physicochemical properties that maximize LNP accumulation in pancreatic islets. While smaller LNPs tend to show higher distribution to the liver and pancreas overall, our findings indicate that, with respect to pancreatic islet accumulation, larger LNPs exhibit superior distribution and accumulation.
 
Potential Applications and Commercialization Prospects

● Diabetes, Pancreatic Diseases, Pancreatic Islets, Nanoparticle Formulations, Nucleic Acid Therapeutics, and Drug Discovery
Using the LNPs developed in this study, we have successfully encapsulated siRNA and mRNA and delivered them into pancreatic islets and β cells. This technology does not require specialized materials or manufacturing processes, suggesting a reduction in implementation and production costs.
This platform is expected to enable the development of novel therapeutics for pancreatic diseases, including type 1 and type 2 diabetes characterized by pancreatic islet dysfunction and reduced islet mass, chronic pancreatitis, and pancreatic cancer.

L-12-1.png

Figure 1. Organ distribution of LNPs depending on lipid composition
DSPC/Chol shows higher distribution to the spleen compared with other compositions.
　		 L-12-2.png
Figure 2. Distribution of LNPs in pancreatic islets according to particle size of DOPC/Chol LNPs
● Diagram explanation
・各LNPの物性評価・IVIS撮像：Physicochemical characterization of each LNP and IVIS imaging
・DLS測定結果：DLS measurement results
・ex vivo 蛍光イメージング(投与24hr後)：Ex vivo fluorescence imaging (24 h post-administration)
・脾臓：Spleen,　膵臓：Pancreas,　肝臓：Liver
・（白点線：脾臓）：White dashed line: spleen		 ・膵島／膵外分泌：Pancreatic islets / Exocrine pancreas
Patents ● WO/2024-253032　“Lipid nanoparticles.”
Publications ● Takayuki Oguma, Takanori Kanazawa, Yukiko K. Kaneko, Ren Sato, Miku Serizawa, Akira Ooka, Momoka Yamaguchi, Tomohisa Ishikawa, Hiromu Kondo, Effects of phospholipid type and particle size on lipid nanoparticle distribution in vivo and in pancreatic islets, Journal of Controlled Release, 2024:373;917–928
DOI　https://doi.org/10.1016/j.jconrel.2024.07.059

Last updated date：October 15, 2026

 

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