title: The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery.
abstract: Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia; Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia; Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia.
authors.forename: Adrian V
authors.initials: AV
authors.lastname: Fuchs
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia; Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia.
authors.forename: Nathan R B
authors.initials: NR
authors.lastname: Boase
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Rolfe
authors.affiliation: The International Medical University, School of Pharmacy, No. 126 Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
authors.forename: Allan G A
authors.initials: AG
authors.lastname: Coombes
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia; Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia; ARC Centre of Excellence in Convergent BioNano Science and Technology, Australia. Electronic address: k.thurecht@uq.edu.au.
authors.forename: Kristofer J
authors.initials: KJ
authors.lastname: Thurecht
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002214:Capsules; D002232:Carbocyanines / Q000737:chemistry; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D005243:Feces / Q000737:chemistry; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D002232:Carbocyanines; D005079:Excipients; D005456:Fluorescent Dyes; C085321:cyanine dye 5
keywords: Animal optical imaging; Chitosan–hypromellose microcapsules; Colorectal cancer; In vivo; Nanoparticles; Oral delivery