Multifunctional organic–inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery

• DOI: 10.2147/ijn.s129311
• Publication Date: 2017-02-28T21:52:06Z
• Authors: Huibo Chi; Yan Gu; Tingting Xu; Feng Cao
• Keywords: Male; Medicine (General); Administration, Ophthalmic; 02 engineering and technology; Cell Line; Cornea; R5-920; Drug Delivery Systems; International Journal of Nanomedicine; Oxazines; Hydroxides; Animals; Humans; Human corneal epithelial primary cell (HCEpic); Organic Chemicals; Original Research; Ocular drug delivery; Chitosan; Cell Death; Active targeting; Epithelial Cells; Flow Cytometry; Endocytosis; 3. Good health; Drug Liberation; Microscopy, Fluorescence; Retinal pigment cell (ARPE-19); Inorganic Chemicals; LDH nanoparticles; Nanoparticles; Ophthalmic Solutions; 0210 nano-technology; LDH nanosheets

To study the cellular uptake mechanism of multifunctional organic-inorganic hybrid nanoparticles and nanosheets, new chitosan-glutathione-valine-valine-layered double hydroxide (CG-VV-LDH) nanosheets with active targeting to peptide transporter-1 (PepT-1) were prepared, characterized and further compared with CG-VV-LDH nanoparticles. Both organic-inorganic hybrid nanoparticles and nanosheets showed a sustained release in vitro and prolonged precorneal retention time in vivo, but CG-VV-LDH nanoparticles showed superior permeability in the isolated cornea of rabbits than CG-VV-LDH nanosheets. Furthermore, results of cellular uptake on human corneal epithelial primary cells (HCEpiC) and retinal pigment epithelial (ARPE-19) cells indicated that both clathrin-mediated endocytosis and active transport of PepT-1 are involved in the internalization of CG-VV-LDH nanoparticles and CG-VV-LDH nanosheets. In summary, the CG-VV-LDH nanoparticle may be a promising carrier as a topical ocular drug delivery system for the treatment of ocular diseases of mid-posterior segments, while the CG-VV-LDH nanosheet may be suitable for the treatment of ocular surface diseases.