2. Academic Validation
  3. Development of cationic solid lipid nanoparticles incorporating cholesteryl-9-carboxynonanoate (9CCN) for delivery of antagomiRs to macrophages

Development of cationic solid lipid nanoparticles incorporating cholesteryl-9-carboxynonanoate (9CCN) for delivery of antagomiRs to macrophages

  • Eur J Pharm Biopharm. 2024 Apr:197:114238. doi: 10.1016/j.ejpb.2024.114238.
Adrian Mallén 1,  David A Narváez-Narváez 2,  M D Pujol 3,  Estanis Navarro 4,  Josep Maria Suñé-Negre 5,  Encarna García-Montoya 6,  Pilar Pérez-Lozano 6,  Benjamín Torrejón-Escribano 7,  Marc Suñé-Pou 8,  Miguel Hueso 9
Affiliations

Affiliations

  • 1 Experimental Nephrology Lab, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Spain. Electronic address: [email protected].
  • 2 Service of Development of Medicines (SDM), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
  • 3 Service of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain. Electronic address: [email protected].
  • 4 Experimental Nephrology Lab, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Spain.
  • 5 Service of Development of Medicines (SDM), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; Pharmacotherapy, Pharmacogenetics and Pharmaceutical Technology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. Electronic address: [email protected].
  • 6 Service of Development of Medicines (SDM), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; Pharmacotherapy, Pharmacogenetics and Pharmaceutical Technology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
  • 7 Advanced Light Microscopy Unit (Bellvitge Campus), Scientific and Technical Facility (CCiTUB), University of Barcelona, L'Hospitalet de LLobregat, Spain. Electronic address: [email protected].
  • 8 Service of Development of Medicines (SDM), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; Pharmacotherapy, Pharmacogenetics and Pharmaceutical Technology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. Electronic address: [email protected].
  • 9 Experimental Nephrology Lab, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Spain; Department of Nephrology, Hospital Universitari Bellvitge, and Institut d'Investigació Biomèdica de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Spain. Electronic address: [email protected].
PMID: 38417704 DOI: 10.1016/j.ejpb.2024.114238
Abstract

Lipid-based nanoparticles are a useful tool for nucleic acids delivery and have been regarded as a promising approach for diverse diseases. However, off-targets effects are a matter of concern and some strategies to improve selectivity of solid lipid nanoparticles (SLNs) were reported. The goal of this study was to test formulations of SLNs incorporating lipid cholesteryl-9-carboxynonanoate (9CCN) as "eat-me" signal to target antagomiR Oligonucleotides to macrophages. We formulate four SLNs, and those with a mean diameter of 200 nm and a Z-potential values between 25 and 40 mV, which allowed the antagomiR binding, were selected for in vitro studies. Cell viability, transfection efficiency and cellular uptake assays were performed within in vitro macrophages using flow cytometry and confocal imaging and the SLNs incorporating 25 mg of 9CCN proved to be the best formulation. Subsequently, we used a labeled antagomiR to study tissue distribution in in-vivo ApoE-/- model of atherosclerosis. Using the ApoE-/- model we demonstrated that SLNs with phagocytic signal 9-CCN target macrophages and release the antagomiR cargo in a selective way.

Keywords

AntagomiR-125b; Cholesteryl-9-carboxynonanoate (9CCN); Macrophage transfection; Nucleic acid delivery; Solid lipid nanoparticles (SLNs); miR-125b.

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