Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat

McGinn, Brian; Morrison, J. D.

doi:10.1016/j.jconrel.2016.04.002

Cited by 7 publications

(6 citation statements)

References 90 publications

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“…Hence, due to the large molecular weight of insulin (5.8 kDa) [14], it would not be suitable to be absorbed through the paracellular route. Moreover, previous studies suggest that the transcellular transport through the enterocytes would be the main route for insulin absorption [15]. In fact, enterocytes present insulin receptors in both their apical and basolateral membranes [16].…”

Section: Introductionmentioning

confidence: 99%

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

et al. 2021

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Zein, the major storage protein from corn, has a GRAS (Generally Regarded as Safe) status and may be easily transformed into nanoparticles, offering significant payloads for protein materials without affecting their stability. In this work, the capability of bare zein nanoparticles (mucoadhesive) and nanoparticles coated with poly(ethylene glycol) (mucus-permeating) was evaluated as oral carriers of insulin (I-NP and I-NP-PEG, respectively). Both nanocarriers displayed sizes of around 270 nm, insulin payloads close to 80 µg/mg and did not induce cytotoxic effects in Caco-2 and HT29-MTX cell lines. In Caenorhabditis elegans, where insulin decreases fat storage, I-NP-PEG induced a higher reduction in the fat content than I-NP and slightly lower than the control (Orlistat). In diabetic rats, nanoparticles induced a potent hypoglycemic effect and achieved an oral bioavailability of 4.2% for I-NP and 10.2% for I-NP-PEG. This superior effect observed for I-NP-PEG would be related to their capability to diffuse through the mucus layer and reach the surface of enterocytes (where insulin would be released), whereas the mucoadhesive I-NP would remain trapped in the mucus, far away from the absorptive epithelium. In summary, PEG-coated zein nanoparticles may be an interesting device for the effective delivery of proteins through the oral route.

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Section: Introductionmentioning

confidence: 99%

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

et al. 2021

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“…The high capacity of the bile acid transporters and high efficacy of both intestinal and liver absorptions make the enterohepatic circulation of bile acids be utilized in oral delivery systems to increase the therapeutic concentration in the liver and reduce the general toxicity of the drugs (Swaan et al., 1996 ; Zhang et al., 2016a ). For insulin delivery, it was evidenced that the bile acid conjugated insulin was taken up by the ileal bile acid transporters after infusion into the small intestine (McGinn & Morrison, 2016 ). Very recently, Fan et al.…”

Section: Introductionmentioning

confidence: 99%

Liver-targeted delivery of insulin-loaded nanoparticles via enterohepatic circulation of bile acids

Zhang

Yao

2018

Drug Delivery

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Liver is the primary acting site of insulin. In this study, we developed innovative nanoparticles for oral and liver-targeted delivery of insulin by using enterohepatic circulation of bile acids. The nanoparticles were produced from cholic acid and quaternary ammonium modified chitosan derivative and hydroxypropyl methylcellulose phthalate (HPMCP). The nanoparticles had a diameter of 239 nm, an insulin loading efficiency of 90.9%, and a loading capacity of 18.2%. Cell culture studies revealed that the cholic acid groups effectively enhanced the transport of the nanoparticles through Caco-2 cell monolayer and greatly increased the absorption of the nanoparticles in HepG-2 cells via bile acid transporter mechanism. Ex vivo fluorescence images of ileum section, gastrointestinal tract, and liver demonstrated that the HPMCP increased the mucoadhesion of the nanoparticles in ileum, and the cholic acid groups facilitated the absorptions of the nanoparticles in both ileum and liver by use of bile acid transporters via enterohepatic circulation of bile acids. The therapy for diabetic mice displayed that the oral nanoparticle group could maintain hypoglycemic effect for more than 24 h and its pharmacological availability was about 30% compared with the insulin injection group. For the first time, this study demonstrates that using enterohepatic circulation of bile acids is an effective strategy for oral delivery of insulin.

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“…Insulin is a hormone necessary in the treatment of type 1 diabetes mellitus and patients with type 2 diabetes advanced stages . However, the subcutaneous administration of insulin is an invasive therapy, and it could produce side effects such as hypoglycemia, allergy, resistance, and lipodystrophy . Several authors propose the oral delivery of insulin as one more appropriate route for the patients and it is considered that mimic the physiological conditions of endogenous insulin in a healthy people and provides better glucose homeostasis .…”

Section: Introductionmentioning

confidence: 99%

“…Due to enzymatic degradation of insulin in the upper gastrointestinal tract, the poor permeability in the intestine and short half‐life, the oral bioavailability of this hormone is very low, which limits its oral administration . Therefore, it is necessary to protect the insulin of digestion by gastro‐intestinal proteases and direct it to sites with lower proteolytic activity such as the colon, where there is evidence of absorption of this peptide …”

Section: Introductionmentioning

confidence: 99%

Electrospray‐assisted fabrication of core‐shell arabinoxylan gel particles for insulin and probiotics entrapment

Paz-Samaniego

Rascón‐Chu²,

Brown

et al. 2018

J of Applied Polymer Sci

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This work presents the fabrication and characterization of electro-sprayed core-shell particles that were composed of maize bran arabinoxylans (MBAX) with insulin in the core, and maize wastewater arabinoxylans (MWAX) with Bifidobacterium in the shell. Two concentrations of MBAX (3% and 6% w/v) and MWAX (6% and 10% w/v) were evaluated. The particles fabricated with MBAX at 6% (w/v) in the core and MWAX at 10% (w/v) in the shell were more stable, presented spherical shape and no aggregation being therefore selected to be loaded with insulin and probiotics. These particles presented a size of 2.9 mm. Scanning electron microscopy analysis of the particle cross section revealed the presence of both, a smooth (shell) and a porous (core) microstructure. Confocal laser scanning microscopy confirmed the core-shell structure of the particles and the viability of the probiotic entrapped. Gastrointestinal simulation strongly suggests that these particles are not degraded in the stomach and small intestine and that 76% of the carried insulin is released in colon. These results indicate that insulin and Bifidobacterium encapsulation by tetraaxial electro spraying can be a feasible and adequate technique to produce arabinoxylan capsules containing both insulin and probiotics. V C 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46411.

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Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat

Cited by 7 publications

References 90 publications

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery

Liver-targeted delivery of insulin-loaded nanoparticles via enterohepatic circulation of bile acids

Electrospray‐assisted fabrication of core‐shell arabinoxylan gel particles for insulin and probiotics entrapment

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