Purchase this article with an account.
Tao L. Lowe, Junjie Zhang, Linfeng Wu, Soohan Chang, Quyen Chim, Xiaoxun Li; Quaternary Ammonium β-Cyclodextrin Nanoparticles as Topotecan Carriers for Treating Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2064.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study is to evaluate our recently developed quaternary ammonium β-cyclodextrin (QAβCD) nanoparticles as sustained topotecan release carriers for the treatment of retinoblastoma, aiming for ocular topical administration of topotecan.
A serial of QAβCD nanoparticles carried various amounts of quaternary ammonium groups were synthesized by a one-step condensation polymerization. For the ex-vivo studies on the QAβCD nanoparticle permeability across different pig ocular tissues, these nanoparticles were labeled with DTAF in order to easily quantify the concentrations of QAβCD nanoparticles. The sizes and Zeta-potentials of these nanoparticles were determined using dynamic light scattering and Zeta potentiometer, respectively. Topotecan was either physically encapsulated or chemically conjugated into these QAβCD nanoparticles. The conjugates were characterized using attenuated total ATR-FTIR and NMR. Studies were then conducted on the release kinetics of topotecan from these topotecan-loaded nanoparticles in phosphate buffered saline solution (pH 7.4) at 37 °C. The MTT assay was used to evaluate the cytotoxicity of these nanoparticles to retinoblastoma Y79 cells. Valia-Chien diffusion cells were used to evaluate the permeability of these nanoparicles across the sclera, sclera-choroid-RPE and cornea of pig.
ATR-FTIR and NMR measurements confirmed the successful synthesis of QAβCD nanoparticles and the conjugation of topotecan to QAβCD nanoparticles. DLS analyses showed that the average hydrodynamic diameters of the DTAF labeled QAβCD nanoparticles were around 78 to 515 nm. MTT data indicated that the QAβCD nanoparticles without topotecan are not cytotoxic to Y79 cells at concentration at least up to 0.5 mg·ml-1. While topotecan physically encapsulated QAβCD nanoparticles can kill Y79 cells as efficiently as topotecan alone but they can sustainably release topotecan for 4 days. The permeability of QAβCD nanoparticles across the sclera and cornea are significantly higher than the control 70 kDa dextran. These nanoparticles are more easily across the sclera than the cornea. The more quaternary ammonium groups are attached to nanoparticles, the higher the permeability of the nanoparticles across the sclera and cornea.
The developed QAβCD nanoparticles have great potential for topically delivering topotecan to treat retinoblastoma.
This PDF is available to Subscribers Only