Hyaluronan-modified core-shell liponanoparticles targeting CD44-positive retinal pigment epithelium cells via intravitreal injection.

Abstract

Retinal inflammation, a common process of posterior ocular diseases, may lead to severe vision loss or even blindness. Retinal pigment epithelium (RPE) cells are generally considered as the therapeutic target of inflammation pathogenesis. However, the lack of retina-specific distribution for general intravitreous drug delivery systems makes the anti-inflammation treatment inefficient. In the present study, a hyaluronan (HA)-modified core-shell liponanoparticles (HA-LCS-NPs) was designed to improve the treatment efficiency by increasing RPE-targeted distribution. Our in vitro RPE cell uptake study showed that a higher HA grafting density (5.8%) and a higher molecular weight (200-400 kDa) modification of HA improved the intracellular uptake of HA-LCS-NPs. In addition, in vivo distribution evaluation in experimental autoimmune uveitis (EAU) rats revealed that HA-LCS-NPs could specifically target RPE cells through the interaction between the CD44 receptor and the HA ligand, while chitosan nanoparticles (CS-NPs) were limited to the vitreous cavity and the core-shell liponanoparticles (LCS-NPs) only reached the inner layers of the retina. At 7 d post-injection, approximately 75% of the fluorescence of HA-LCS-NPs still remained in the RPE/choroid. In conclusion, HA-LCS-NPs might present a promising intraocular drug delivery system to achieve RPE-targeted distribution and prolonged intraocular residence.

• Authors: Li Gan, Jing Wang, Yanan Zhao, Dan Chen, Chunliu Zhu, Jianping Liu, Yong Gan
• Journal: Biomaterials (Biomaterials) Vol. 34 Issue 24 Pg. 5978-87 (Aug 2013) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 23680367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Hyaluronan Receptors
• Lipids
• Hyaluronic Acid
• Chitosan

Topics

• Animals
• Cell Survival (drug effects)
• Chitosan (pharmacology)
• Drug Delivery Systems
• Endocytosis (drug effects)
• Epithelial Cells (drug effects, metabolism, pathology)
• Fluorescence
• Humans
• Hyaluronan Receptors (metabolism)
• Hyaluronic Acid (administration & dosage, pharmacology)
• Immunohistochemistry
• Intravitreal Injections
• Lipids (chemistry)
• Molecular Weight
• Nanoparticles (administration & dosage, ultrastructure)
• Particle Size
• Rats
• Rats, Inbred Lew
• Retinal Pigment Epithelium (pathology)
• Static Electricity
• Uveitis (pathology)