A Multifunctional Hybrid Nanocarrier for Non-Invasive siRNA Delivery to the Retina

Drug therapy for retinal diseases (e.g., age-related macular degeneration, the leading cause of blindness) is generally performed by invasive intravitreal injection because of poor drug delivery caused by the blood-retinal barrier (BRB). This study aimed to develop a nanocarrier for the non-invasive...

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Bibliographic Details
Published in:Pharmaceutics 2023-02, Vol.15 (2), p.611
Main Authors: Nishida, Shogo, Takashima, Yuuki, Udagawa, Ryotaro, Ibaraki, Hisako, Seta, Yasuo, Ishihara, Hiroshi
Format: Article
Language:English
Subjects:
Diabetic retinopathy
Disease
Drug delivery systems
Drug therapy
Drugs
Flow cytometry
functional peptide
Gene expression
instillation
Lipids
Materials
Nanomedicine
Particle size
Peptides
Retina
retina pigment epithelium cells
Retinal diseases
siRNA
siRNA delivery
Vascular endothelial growth factor
VEGF
Vehicles
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Summary:Drug therapy for retinal diseases (e.g., age-related macular degeneration, the leading cause of blindness) is generally performed by invasive intravitreal injection because of poor drug delivery caused by the blood-retinal barrier (BRB). This study aimed to develop a nanocarrier for the non-invasive delivery of small interfering RNA (siRNA) to the posterior segment of the eye (i.e., the retina) by eyedrops. To this end, we prepared a hybrid nanocarrier based on a multifunctional peptide and liposomes, and the composition was optimized. A cytoplasm-responsive stearylated peptide (STR-CH2R4H2C) was used as the multifunctional peptide because of its superior ability to enhance the complexation, cell permeation, and intracellular dynamics of siRNA. By adding STR-CH2R4H2C to the surface of liposomes, intracellular uptake increased regardless of the liposome surface charge. The STR-CH2R4H2C-modified cationic nanocarrier demonstrated significant siRNA transfection efficiency with no cytotoxicity, enhanced siRNA release from endosomes, and effectively suppressed vascular endothelial growth factor expression in rat retinal pigment epithelium cells. The 2.0 mol% STR-CH2R4H2C-modified cationic nanocarrier enhanced intraocular migration into the retina after instillation into rat eyes.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15020611