title: Bifunctional Succinylated ε-Polylysine-Coated Mesoporous Silica Nanoparticles for pH-Responsive and Intracellular Drug Delivery Targeting the Colon.
abstract: Conventional oral drug formulations for colonic diseases require the administration of high doses of drug to achieve effective drug concentrations at the target site. However, this exposes patients to serious systemic toxicity in order to achieve efficacy. To overcome this problem, an oral drug delivery system was developed by loading a large amount (ca. 34% w/w) of prednisolone into 3-aminopropyl-functionalized mesoporous silica nanoparticles (MCM-NH2) and targeting prednisolone release to the colon by coating the nanoparticle with succinylated ε-polylysine (SPL). We demonstrate for the first time the pH-responsive ability of SPL as a "nanogate" to selectively release prednisolone in the pH conditions of the colon (pH 5.5-7.4) but not in the more acidic conditions of the stomach (pH 1.9) or small intestine (pH 5.0). In addition to targeting drug delivery to the colon, we explored whether the nanoparticles could deliver cargo intracellularly to immune cells (RAW 264.7 macrophages) and intestinal epithelial cells (LS 174T and Caco-2 adenocarcinoma cell lines). To trace uptake, MCM-NH2were loaded with a cell membrane-impermeable dye, sulforhodamine B. The SPL-coated nanoparticles were able to deliver the dye intracellularly to RAW 264.7 macrophages and the intestinal epithelial cancer cells, which offers a highly promising and novel drug delivery system for diseases of the colon such as inflammatory bowel disease and colorectal cancer.
authors.forename: Chau T H
authors.initials: CT
authors.lastname: Nguyen
authors.forename: Richard I
authors.initials: RI
authors.lastname: Webb
authors.forename: Lynette K
authors.initials: LK
authors.lastname: Lambert
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Strounina
authors.forename: Edward C
authors.initials: EC
authors.lastname: Lee
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Parat
authors.affiliation: Translational Research Institute, Inflammatory Disease Biology and Therapeutics Group, Mater Research Institute - The University of Queensland , 37 Kent St., Woolloongabba, Queensland 4102, Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: McGuckin
authors.affiliation: Translational Research Institute, Inflammatory Disease Biology and Therapeutics Group, Mater Research Institute - The University of Queensland , 37 Kent St., Woolloongabba, Queensland 4102, Australia.
authors.forename: Amirali
authors.initials: A
authors.lastname: Popat
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cabot
authors.forename: Benjamin P
authors.identifier: http://orcid.org/0000-0002-1899-8484
authors.initials: BP
authors.lastname: Ross
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053758:Nanoparticles; D011107:Polylysine; D016062:Porosity; D012822:Silicon Dioxide
chemical_list: D011107:Polylysine; D012822:Silicon Dioxide
keywords: colon targeted drug delivery; intracellular drug delivery; mesoporous silica nanoparticles; pH-responsive; prednisolone; succinylated ε-polylysine