Intestinal mucosa permeability following oral insulin delivery using core shell corona nanolipoparticles

Li, Xiuying; Guo, Shiyan; Zhu, Chunliu; Zhu, Quanlei; Gan, Yong; Rantanen, Jukka; Rahbek, Ulrik Lytt; Hovgaard, Lars; Yang, Mingshi

doi:10.1016/j.biomaterials.2013.08.048

Cited by 136 publications

(59 citation statements)

References 36 publications

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“…To quantify the distribution patterns of the NPs, the mucin fibers were stained with Alexa Fluor 488-conjugated wheat germ agglutinin (WGA), and particle solutions were injected into ligated intestinal loops, followed by a 30-min incubation with gentle agitation 38 . To determine whether aggregation of the MSNSs hampered the mucus-penetrating process of the nanospheres, we decorated the NPs with a high density of PEG to further study the ability of these particles to penetrate mucus.…”

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confidence: 99%

Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues

et al. 2016

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Mucus is a viscoelastic gel layer that typically protects exposed surfaces of the gastrointestinal (GI) tract, lung airways, and other mucosal tissues. Particles targeted to these tissues can be efficiently trapped and removed by mucus, thereby limiting the effectiveness of such drug delivery systems. In this study, we experimentally and theoretically demonstrated that cylindrical nanoparticles (NPs), such as mesoporous silica nanorods and calcium phosphate nanorods, have superior transport and trafficking capability in mucus compared with spheres of the same chemistry. The higher diffusivity of nanorods leads to deeper mucus penetration and a longer retention time in the GI tract than that of their spherical counterparts. Molecular simulations and stimulated emission of depletion (STED) microscopy revealed that this anomalous phenomenon can be attributed to the rotational dynamics of the NPs facilitated by the mucin fibers and the shear flow. These findings shed new light on the shape design of NP-based drug delivery systems targeted to mucosal and tumor sites that possess a fibrous structure/porous medium.

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confidence: 99%

Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues

et al. 2016

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“…Protection of INS against enzymatic degradation by surfactin was evaluated in vitro Li et al, 2013). Briefly, INS (1 mg/ml) mixed with or without surfactin (1 mg/ml), was incubated at 37 C with 0.1% (w/v) pepsin at pH 1.2, or with 0.1% (w/v) trypsin at pH 6.8 for 30 min.…”

Section: Analysis Of Surfactin To Protect Ins From Pepsin and Trypsinmentioning

confidence: 99%

A natural lipopeptide of surfactin for oral delivery of insulin

et al. 2016

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Surfactin, a natural lipopeptide produced by Bacillus, is gaining attention for potentially biomedical and pharmaceutical applications. Here, surfactin was assayed for oral delivery of insulin (INS) by its ability to bind to and promote protein to penetrate through the cell membrane. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, surfactin was found to form co-precipitates with INS to protect it from acidic and enzymatic attack in the gastrointestinal tract. Further analysis by non-reductive electrophoresis showed surfactin could bind to INS forming heteropolymers. Analysis with circular dichroism, we found this binding significantly influenced the INS structure with decreased rigid a-helix and b-turn, but with increased flexible b-sheet and random coil. The change with more flexible structure was favorable for INS to penetrate through the cell membrane. Fluorescence spectra analysis also showed surfactin could lead Phe and Tyr in the inner of INS exposed outside, further promoting INS permeabilization by improving the hydrophobic-lipophilic interactions between INS and cell membrane. As a result, the effective permeability (Peff) of INS plus surfactin was 4.3 times of that of INS alone. In vivo assay showed oral INS with surfactin displayed excellent hypoglycemic effects with a relative bioavailability of 12.48% and 5.97% in diabetic mice and non-diabetic dogs, respectively. Summary, surfactin is potential for oral delivery of INS by its role as an effective protease inhibitor and permeability enhancer.

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“…[9][10][11] In addition, the intestinal epithelium is another major obstacle to the absorption of hydrophilic macromolecules, as it is difficult for insulin to cross the lipid bilayer cell membrane. [12][13][14] In order to overcome these obstacles mentioned and to enhance the oral bioavailability of insulin, biodegradable polymeric nanoparticles (NPs) such as poly(lactic acid), poly(glycolic acid), and their copolymers poly(lactide-co-glycolide) (PLGA) NPs have been widely studied by our group.…”

Section: Introductionmentioning

confidence: 99%

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

Sun¹,

Liang²,

Yamamoto³

et al. 2015

IJN

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This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide) (PLGA) nanoparticle composite microcapsules for oral delivery of insulin. Firstly, insulin–sodium oleate complex was prepared by the hydrophobic ion pairing method and then encapsulated into PLGA nanoparticles by the emulsion solvent diffusion method. In order to reduce the burst release of insulin from PLGA nanoparticles and deliver insulin to specific gastrointestinal regions, hence to enhance bioavailability of insulin, the PLGA nanoparticles were further encapsulated into Eudragit ® FS 30D to prepare PLGA nanoparticle composite microcapsules by organic spray-drying method. The preparation was evaluated in vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug release studies revealed that the drug release was pH dependent, and the in vivo results demonstrated that the formulation of PLGA nanoparticle composite microcapsules was an effective candidate for oral insulin delivery.

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Intestinal mucosa permeability following oral insulin delivery using core shell corona nanolipoparticles

Cited by 136 publications

References 36 publications

Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues

Rotation-Facilitated Rapid Transport of Nanorods in Mucosal Tissues

A natural lipopeptide of surfactin for oral delivery of insulin

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

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