Gastrointestinal Delivery of Anti-inflammatory Nanoparticles

Laroui, Hamed; Sitaraman, Shanthi V.; Merlin, Didier

doi:10.1016/b978-0-12-391858-1.00006-x

Cited by 33 publications

(20 citation statements)

References 90 publications

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“…The delivery of siRNA to target tissues via traditional agents (e.g., Lipofectamine) are complicated because naked siRNA lacks stability and shows poor tissue penetration [20-22]. In the other hand, the pre-complexation of siRNA with low molecular weight polyethyleneimine (PEI) has been shown to protect against degradation, enhance drug loading, and increase siRNA lysosome-escape ability via the “proton sponge effect” [18, 23]. …”

Section: Introductionmentioning

confidence: 99%

Fab'-bearing siRNA TNFα-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis

Laroui

Viennois

Xiao

et al. 2014

Journal of Controlled Release

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130

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Patients suffering from Inflammatory Bowel Disease (IBD) are currently treated by systemic drugs that can have significant side effects. Thus, it would be highly desirable to target TNFα siRNA (a therapeutic molecule) to the inflamed tissue. Here, we demonstrate that TNFα siRNA can be efficiently loaded into nanoparticles (NPs) made of poly (lactic acid) poly (ethylene glycol) block copolymer (PLA-PEG), and that grafting of the Fab’ portion of the F4/80 Ab (Fab’-bearing) onto the NP surface via maleimide/thiol group-mediated covalent bonding improves the macrophage (MP)-targeting kinetics of the NPs to RAW264.7 cells in vitro. Direct binding was shown between MPs and the Fab’-bearing NPs. Next, we orally administered hydrogel (chitosan/alginate)-encapsulated Fab’-bearing TNFα-siRNA-loaded NPs to 3% dextran sodium sulfate (DSS)-treated mice and investigated the therapeutic effect on colitis. In vivo, the release of TNFα-siRNA-loaded NPs into the mouse colon attenuated colitis more efficiently when the NPs were covered with Fab’-bearing, compared to uncovered NPs. All DSS-induced parameters of colonic inflammation (e.g., weight loss, myeloperoxidase activity, and Iκbα accumulation) were more attenuated Fab’-bearing NPs loaded with TNFα siRNA than without the Fab’-bearing. Grafting the Fab’-bearing onto the NPs improved the kinetics of endocytosis as well as the MP-targeting ability, as indicated by flow cytometry. Collectively, our results show that Fab’-bearing PLA-PEG NPs are powerful and efficient nanosized tools for delivering siRNAs into colonic macrophages.

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Section: Introductionmentioning

confidence: 99%

Fab'-bearing siRNA TNFα-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis

Laroui

Viennois

Xiao

et al. 2014

Journal of Controlled Release

Self Cite

130

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“…The administration and the chelation of the hydrogel were realized using a double gavage method as previously described. 29 Immunofluorescence Detection of NF-jB-p65 Complex Raw 264.7 macrophages were seeded in eight-chamber tissue culture glass slide (BD Falcon, Bedford, MA, USA) at a density of 2 Â 10 4 cells/well and incubated overnight. The cells were incubated for 8 h with 5 mM of PTL, MCL, or the DMSO control and then induced by 10 mg/ml of LPS for 30 min.…”

Section: Encapsulation Of Dmapt or Dmamcl Into Hydrogelmentioning

confidence: 99%

Micheliolide, a new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer

Viennois

Xiao

Ayyadurai

et al. 2014

Laboratory Investigation

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Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal (GI) tract associated with an increased risk of colorectal cancer (CRC). Current treatments for both IBD and colitis-associated CRC suffer from numerous side effects. Parthenolide (PTL) is a sesquiterpene lactone with anti-inflammatory activity, and previous studies have demonstrated that PTL is a potent inhibitor of the NF-kB pathway. Micheliolide (MCL), substantially more stable than PTL in vivo, was recently developed, and this study aimed to decipher its suitability as therapeutic tool for IBD and IBDassociated diseases. Similar to PTL, MCL inhibited NF-kB activation and subsequent pro-inflammatory pathways activation in vitro. Pro-drug forms of both compounds inhibited the DSS-induced colitis when administrated intraperitoneally or encapsulated in a polysaccharide gel designed to release drugs in the colon. Interestingly, MCL was found to attenuate carcinogenesis in AOM/DSS-induced CRC, thus providing new candidate for the treatment of inflammatory bowel disease and CRC.Laboratory Investigation (2014) 94, 950-965;

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“…8 They can also be used for delivery of drugs such as doxorubicin, platinum compounds, anti-inflammatory drugs, and prodrugs. [9][10][11][12] SPIONs are interesting nanoparticles with clinical potential both in the imaging field and for drug delivery.…”

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confidence: 99%