NANOPARTICLES FOR TARGETED RETINAL DELIVERY
Nanoparticles are useful carriers for intravitreal injection. Besides reducing the injection frequency, they have the potential to enhance the therapeutic benefits of different ocular drugs by localizing and delivering the cargoes to specific types of cells in retina. Given that the retina consists of multiple cell types arranged in distinctive layers, we aim to achieve cell targeting by engineering the size, charge and surface modification of the nanoparticles.
POLYMERIC NANOPARTICLES FOR RPE-TARGETING DELIVERY
Retinal pigment epithelium (RPE) is a target site for drug delivery to the posterior segment of the eye. The dysfunction of RPE plays an important role in the pathological development of ocular diseases, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In AMD, abnormal RPE cells trigger choroidal neovascularization (CNV) in the subretinal macular region by the secretion of vascular endothelial growth factor (VEGF). Anatomically, RPE forms the outer blood-retinal barrier to tightly regulate the transport between neuro-retina and choroidal blood vessels. Thus, when nano-drug carriers are injected into the vitreous, RPE represents an important gate keeper before they are cleared dynamically into the blood circulation. On the other hand, folic acid is actively transported by RPE cells via folate-receptors, which are only present in this cell layer in retina.
Based on this knowledge about RPE, we formulated nanoparticles to take advantage of folate-receptors as specific portals to deliver triamcinolone to RPE cells. This approach decreased the drug cytotoxicity associated with poor solubility, while enhancing and prolonging the anti-angiogenic effect of triamcinolone.
Based on this knowledge about RPE, we formulated nanoparticles to take advantage of folate-receptors as specific portals to deliver triamcinolone to RPE cells. This approach decreased the drug cytotoxicity associated with poor solubility, while enhancing and prolonging the anti-angiogenic effect of triamcinolone.
LIPID-BASED NANOPARTICLES FOR RETINAL-TARGETING DELIVERY
Drug delivery to the retina for the treatment of common retinal diseases including glaucoma, age-related macular degeneration and diabetic retinopathy remains challenging, especially for the emerging RNAi therapeutics. To achieve retinal targeting, intravitreally injected nanoparticles have been extensively employed as drug delivery carriers. The physicochemical properties of intravitreal nanoparticles significantly impact on their intraocular transport and retinal distribution, eventually the drug treatment efficacy. However, there is limited understanding of the correlation of the nanoparticle properties with their intraocular behaviors and drug delivery efficiency.
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To achieve targeted retinal drug delivery (such as siRNA) via engineered nanoparticles, this project has 3 aims:
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Barriers in retinal delivery
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Related publications
- Huang, X., & Chau, Y. (2020). Enhanced Delivery of siRNA to Retinal Ganglion Cells by Intravitreal Lipid Nanoparticles of Positive Charge. Molecular Pharmaceutics.
- Huang X, Chau Y, Investigating impacts of surface charge on intraocular distribution of intravitreal lipid nanoparticles, Experimental Eye Research, 2019,186, 107711 DOI: 10.1016/j.exer.2019.10771
- Huang X, Chau Y, Intravitreal nanoparticles for retinal delivery, Drug Discovery Today, (24) 2019, 1510-1523, DOI: 10.1016/j.drudis.2019.05.005
- Suen, W.-L.L., Chau, Y. “Size-dependent internalization of folate-decorated nanoparticles via the pathways of clathrin- and caveolae-mediated endocytosis in ARPE-19 cells” 2014 . Journal of Pharmacy and Pharmacology. 66(4):564-573.
