title: 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.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing; State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research Co., Ltd., Tianjin, People's Republic of China.
authors.forename: Huibo
authors.initials: H
authors.lastname: Chi
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing.
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D003315:Cornea / Q000187:drug effects; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D006878:Hydroxides / Q000737:chemistry*; D007287:Inorganic Chemicals / Q000737:chemistry*; D008297:Male; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D009930:Organic Chemicals / Q000737:chemistry*; D010078:Oxazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D011817:Rabbits
chemical_list: D006878:Hydroxides; D007287:Inorganic Chemicals; D009883:Ophthalmic Solutions; D009930:Organic Chemicals; D010078:Oxazines; C004580:pirenoxine; D048271:Chitosan
keywords: ARPE-19; LDH nanoparticles; LDH nanosheets; active targeting; human corneal epithelial primary cell; ocular drug delivery; retinal pigment cell