title: Designing colon-specific delivery systems for anticancer drug-loaded nanoparticles: an evaluation of alginate carriers.
abstract: Incorporation of drug-loaded nanoparticles (NPs) in colon-specific delivery systems shows potential for raising local drug concentrations, tumor targeting and improving chemotherapy. Alginate microcapsules (15-80 µm diameter) containing insoluble Eudragit(®) RS NPs as models were characterized precisely in terms of NP loading and release kinetics. High NP loading (22%, w/w of the dried microcapsules) combined with negligible release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) suggested that high concentrations of NPs could be transported to the colon. However, NP aggregation was confirmed at extremely low concentration (0.0003%, w/v) in alginate solution (0.007%, w/v) and after release from alginate microcapsules. Indomethacin, a model anticolorectal cancer drug, was encapsulated in pH-responsive Eudragit(®) S100 NPs (116 nm, 5%, w/w drug loading) using the nanoprecipitation method. Approximately 90% of the drug load was released from the NPs in SGF and SIF before transfer to simulated colon fluid (SCF). However, incorporation of NPs in 2 mm alginate pellets resulted in a significantly higher fraction of the drug load (around 60%) being available for release in SCF. Delivery of isolated NPs to the colon for interaction with and uptake by cancer cells requires elimination of NP-excipient interactions that promote NP aggregation. NP-loaded alginate carriers, meanwhile, offer a promising strategy for delivery of anticancer drugs to tumor sites in the colon and reducing systemic side effects.
authors.affiliation: Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, Queensland, 4102, Australia.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Ma
authors.forename: Allan G A
authors.initials: AG
authors.lastname: Coombes
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D053758:Nanoparticles / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*
chemical_list: D000464:Alginates; D000970:Antineoplastic Agents; D004337:Drug Carriers; D006603:Hexuronic Acids; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D020723:Glucuronic Acid; D007213:Indomethacin
keywords: Eudragit nanoparticles; aggregation; alginate microcapsules; colorectal cancer; transmission electron microscopy