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L. Wu, E. S. Gil, T. L. Lowe; β-Cyclodextrin-Based Nanoparticles for Drug Delivery across the Blood Retinal/Brain Barriers. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3485.
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© ARVO (1962-2015); The Authors (2016-present)
The blood retinal/brain barrier (BRB/BBB) is a selective and protective barrier preventing adverse components from entering the eye/brain from the blood, but also a formidable obstacle to overcome when trying to deliver therapeutic agents to the eye/brain. The purpose of this study is to develop novel β-cyclodextrin-poly(amino ester) nanoparticles for enhancing the permeability of drugs across the BRB/BBB.
Michael addition reaction method was used to synthesize a series of β-cyclodextrin-poly(amino ester) nanoparticles with crosslinked structure. The chemical, physical and degradation properties of the nanoparticles were characterized using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and atomic force microscopy (AFM). Model drug, doxorubicin (DOX), was loaded into the nanoparticles in dimethyl sulfoxide by diffusion. Studies were conducted on the release kinetics of DOX from the nanoparticles in phosphate buffered saline solution (PBS, pH 7.4) at 37 °C. The MTT assay was used to evaluate the cytotoxicity of the nanoparticles to human/bovine brain microvascular endothelial cells. Human/bovine brain microvascular endothelial cell monolayers were used as in vitro BRB/BBB models to assess the effects of the nanoparticles on the BRB/BBB permeability of DOX.
ATR-FTIR and NMR measurements confirmed the successful synthesis of the β-cyclodextrin-poly(β-amino ester) nanoparticles. DLS and AFM analyses showed that the hydrodynamic diameters of the nanoparticles were around 20 to 400 nm. ATR-FTIR measurements also revealed that the nanoparticles degraded in PBS (pH 7.4) through the mechanism of the cleavage of their ester bonds. The nanoparticles can sustain DOX release for 16 days. MTT data indicated that the nanoparticles are not cytotoxic to human/bovine brain microvascular endothelial cells at concentration up to 0.5 mg·ml-1. The permeability tests demonstrated that the nanoparticles were more permeable than 4kDa dextran control.
The newly developed β-cyclodextrin-poly(β-amino ester) nanoparticles have great potential for delivering drugs across the BRB/BBB to treat retinoblastoma, brain tumors and other diseases in the eye and brain.
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