Hybrid lipid self-assembling nanoparticles for brain delivery of microRNA.

Abstract

Hybrid self-assembling nanoparticles (SANPs) have been previously designed as novel drug delivery system that overcomes stability issues following long-term storage and with an easy scale-up. This system has been successfully used to deliver anionic-charged agents, e.g. bisphosphonates, in different types of tumors, such glioblastoma (GBM). Here, SANPs were tested and optimized for the delivery of nucleic acids, in particular of a specific microRNA, e.g. miR603, used for its potential role in controlling the chemoresistance in different forms of cancer, e.g. (GBM). To this aim, SANPs with different lipids were prepared and characterized, in terms of size, polydispersity index, zeta potential, miRNA encapsulation, stability in BSA, serum and hemolytic activity. Then, SANPs were tested in vitro on two different cell lines of GBM. Finally, miRNA biodistribution was tested in vivo in an orthotopic model of GBM. The majority of the formulations showed good technological characteristics and were stable in BSA and serum with a low hemolytic activity. The intracellular uptake studies on GBM cell lines showed that SANPs allow to achieve a higher miRNA delivery compared to others transfection agents, e.g. lipofectamine. Finally, in vivo biodistribution studies in an orthotopic of GBM demonstrated that the optimized SANP formulations, were able to deliver miRNA in different organs, e.g. the brain.

• Authors: Virginia Campani, Silvia Zappavigna, Lorena Scotti, Marianna Abate, Manuela Porru, Carlo Leonetti, Michele Caraglia, Giuseppe De Rosa
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 588 Pg. 119693 (Oct 15 2020) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 32755686 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Lipids
• MicroRNAs

Topics

• Animals
• Biological Transport
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Gene Transfer Techniques
• Glioblastoma (genetics, metabolism, pathology)
• Humans
• Lipids (chemistry)
• Male
• Mice, SCID
• MicroRNAs (genetics, metabolism)
• Nanoparticles
• Proof of Concept Study
• RNA Stability