Purpose The purpose of this study is to evaluate our recently developed quaternary ammonium β-cyclodextrin (QAbCD) nanoparticlesacross the cornea and sclera of porcine, aiming for providing a nano-size vehicle which can penetrate cornea and sclera.
Methods A serial of QAbCD nanoparticles carried various amounts of quaternary ammonium groups were synthesized by a one-step condensation polymerization]. For the ex-vivo studies on the QAbCD nanoparticles with different quaternary ammonium groups permeability across freshly excised porcine cornea, scleras, with or without the underlying choroid–Bruch’s layer, respectively, these nanoparticles were labeled using 5-(4,6-dichlorotriazinyl) aminofluorescein (DTAF) in order to easily quantify the concentrations of QAbCD nanoparticles. Fluorescein isothiocyanate-dextrans with 4k and 70k molecular weight were used as the control. The sizes and Zeta-potentials of these nanoparticles were determined using dynamic light scattering (DLS) and Zeta potentiometer, respectively. Valia-Chien diffusion cells were used to evaluate the permeability of these nanoparicles across the porcine sclera, sclera-choroid-RPE and cornea.
Results ATR-FTIR and NMR measurements confirmed the successful synthesis of QAbCD nanoparticles. The nanoparticles were composed ofβ-cyclodextran(1)-Epichlorohydrin(15)-Choline-choloride(n), and the different nanoparticles formulations were 15-0, 15-1, 15-2, 15-4 and 15-6, respectively. DLS analyses showed that the average hydrodynamic diameters of the DTAF labeled QAbCD nanoparticles were around 78 nm. The order of the permeability coefficients (Pco) across sclera was 15-4 > 15-2 >15-6 > 15-1 > 15-0 > 4k dextran > 70k dextran. The Pco of 15-0, 15-1, 15-2, 15-4 and 15-6 nanoparicles across the sclera was 16, 18, 33, 41 and 25 times higher than 4k dextran, was 52, 58, 104, 129 and 78 times higher than 70k dextran, respectively. The Pco of 15-0, 15-1, 15-2, 15-4 and 15-6 nanoparicles across the sclera-choroid-RPE was 5, 9, 7, 10 and 23 times higher than 4k dextran, was 54, 100, 75, 110 and 242 times higher than 70k dextran, respectively. The Pco of 15-0, 15-1, 15-2, 15-4 and 15-6 nanoparicles across the cornea was 30, 42, 15, 90 and 58 times higher than 70k dextran, respectively. These nanoparticles are more easily across the sclera than the cornea.
Conclusions The more quaternary ammonium groups are attached to nanoparticles, the higher the permeability of the nanoparticles across the sclera and cornea. The choroid–Bruch’s layer is a more significant barrier to drug transport than sclera. The recently developed QAbCD nanoparticles have great potential for delivering drug across ocular barrier as topical application. |
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