High drug payload nanoparticles formed from dexamethasone-peptide conjugates for the treatment of endotoxin-induced uveitis in rabbit
Open Access
- 1 January 2019
- journal article
- research article
- Published by Taylor & Francis Ltd in International Journal of Nanomedicine
- Vol. ume 14, 591-603
- https://doi.org/10.2147/ijn.s179118
Abstract
Purpose: To develop and demonstrate the effectiveness of a novel dexamethasone (Dex) nanoformulation for treating uveitis. Materials and methods: We designed and screened a dexamethasone-peptide conjugate (Dex-SA-FFFE), formed via a biodegradable ester bond linkage, that could spontaneously form high drug payload nanoparticles in aqueous solution for treating uveitis. Results: An in vitro release study indicated that Dex and Dex-SA-FFFE sustainably released from Dex-SA-FFFE nanoparticles over a 48 h study period. Meanwhile, the formed Dex-SA-FFFE nanoparticles hardly caused cytotoxicity in human corneal epithelial cell at drug concentrations up to 1 mM after 24 h of incubation but reduced cell viability after 48 h and 72 h of incubation. An in vitro anti-inflammatory efficacy assay showed that the Dex-SA-FFFE nanoparticles exhibited a comparable anti-inflammatory efficacy to that of Dex in lipopolysaccharide (LPS)-activated RAW264.7 macrophages via significant decreases in the secretion of various pro-inflammatory cytokines (e.g., nitric oxide, tumor necrosis factor-α, interleukin-6). Topical instillation of Dex-SA-FFFE nanoparticles showed good ocular tolerance without causing changes in corneal thickness and intraocular pressure during the entire study period. Furthermore, topical instillation of Dex-SA-FFFE nanoparticles displayed a comparable in vivo therapeutic efficacy to that of dexamethasone sodium phosphate (Dexp) aqueous solutions in an endotoxin-induced uveitis (EIU) rabbit model. Conclusion: Based on these results, it is reasonable to believe that the proposed Dex-SA-FFFE nanoparticles might have great application for the treatment of anterior uveitis.Keywords
This publication has 44 references indexed in Scilit:
- d-Amino Acids Boost the Selectivity and Confer Supramolecular Hydrogels of a Nonsteroidal Anti-Inflammatory Drug (NSAID)Journal of the American Chemical Society, 2012
- Nanomaterials for Ocular Drug DeliveryMacromolecular Bioscience, 2012
- Feasibility of Lipid Nanoparticles for Ocular Delivery of Anti-Inflammatory DrugsCurrent Eye Research, 2010
- Interaction of colloidal gold nanoparticles with human blood: effects on particle size and analysis of plasma protein binding profilesNanomedicine: Nanotechnology, Biology and Medicine, 2009
- Recent Perspectives in Ocular Drug DeliveryPharmaceutical Research, 2008
- Ocular novel drug delivery: impacts of membranes and barriersExpert Opinion on Drug Delivery, 2008
- Prodrugs: design and clinical applicationsNature Reviews Drug Discovery, 2008
- Large Neutral Amino Acid Transporter Enables Brain Drug Delivery via ProdrugsJournal of Medicinal Chemistry, 2008
- Comparison of Topical Steroids for Acute Anterior UveitisJournal of Ocular Pharmacology and Therapeutics, 2004
- Locally Administered Ocular CorticosteroidsDrug Safety, 2002