Oral colon delivery of insulin with the aid of functional adjuvants

Maroni, Alessandra; Zema, L.; Curto, Del; Foppoli, Anastasia; Gazzaniga, A.

doi:10.1016/j.addr.2011.10.006

Cited by 108 publications

(71 citation statements)

References 193 publications

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“…However, it is undeniable that some barriers against the drug diffusion and permeation exist in colon, which exert a DOI: 10.3109/10717544.2015.1048489 negative influence on colonic absorption of the drug (Philip & Philip, 2010;Maroni et al, 2012). Many attempts have been conducted to overcome the obstacles.…”

Section: Discussionmentioning

confidence: 99%

“…For example, absorption enhancers were used to promote the drug permeation and absorption, with definite toxicity and with little effect on overcoming the barrier against the drug diffusion (Patel, 2013). Due to the fact that the mucous layer in colon is thick and turnover rate slowly and it is insensitive to mucus secretion stimulation (Maroni et al, 2012), the benefits of mucoadhesive polymeric systems were exploited, while the barrier against the drug penetration remained to be overcome ( Van den Mooter, 2006;McGirr et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

“…However, there are still some barriers against absorption of the drug in colon, for example, the barriers against the drug diffusion from colon lumen toward the absorptive mucosa and permeation across colon epithelium. Colon exhibits a wide lumen that limits a close contact between the absorptive epithelium and the contents (Varum et al, 2008), and the contents in colon are quite sticky and hardly flowable which impede the drug diffusion and attachment to mucosa (Varum et al, 2008;Maroni et al, 2012). Moreover, colonic absorption of proteins and peptides has remained to be a great challenge owing to the low permeability across the colonic epithelium membrane caused by inherent high molecular weight and hydrophilicity of the drug, and the narrow tight junctions may impose restrictions on its paracellular permeability (Maroni et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Colon exhibits a wide lumen that limits a close contact between the absorptive epithelium and the contents (Varum et al, 2008), and the contents in colon are quite sticky and hardly flowable which impede the drug diffusion and attachment to mucosa (Varum et al, 2008;Maroni et al, 2012). Moreover, colonic absorption of proteins and peptides has remained to be a great challenge owing to the low permeability across the colonic epithelium membrane caused by inherent high molecular weight and hydrophilicity of the drug, and the narrow tight junctions may impose restrictions on its paracellular permeability (Maroni et al, 2012). As a result, colonic absorption of the drug should be still rather poor (Varum et al, 2008;Maroni et al, 2012;Patel, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, colonic absorption of proteins and peptides has remained to be a great challenge owing to the low permeability across the colonic epithelium membrane caused by inherent high molecular weight and hydrophilicity of the drug, and the narrow tight junctions may impose restrictions on its paracellular permeability (Maroni et al, 2012). As a result, colonic absorption of the drug should be still rather poor (Varum et al, 2008;Maroni et al, 2012;Patel, 2013). In the present study, modified nanoparticles (Tat-CS-NPs) with cellpenetrating peptides (CPPs) (Tat) and amphipathic chitosan derivative (a-CS) were devised as vehicles of the drug to overcome above bottlenecks in oral colon delivery.…”

Section: Introductionmentioning

confidence: 99%

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Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation

et al. 2015

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(2016) Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation, Drug Delivery, 23:6, 2003-2014, DOI: 10.3109/10717544.2015 AbstractColon is an ideal absorptive site for oral protein and peptide drug (insulin), and yet it poses multiple barriers against the drug absorption, such as the barriers against the drug diffusion from colon lumen toward the absorptive mucosa and permeation across colon epithelium. In this study, modified nanoparticles (Tat-CS-NPs) with cell-penetrating peptide (Tat) and amphipathic chitosan derivative (a-CS) were used as carriers to improve colonic absorption of the drug. With a-CS as emulsifier and poly(lactic-co-glycolic acid) as matrix material, Tat-CS-NPs were prepared and evaluated in vitro/vivo. Using Caco-2 cell monolayers to imitate the colonic epithelial cells, it was found that the cellular uptake amount and transcellular transportation performance of Tat-CS-NPs were much enhanced compared with those of CS-NPs and PVA-NPs. The efficacy evaluation on diabetic rat models demonstrated that the hypoglycemic effect of Tat-CS-NPs loaded with insulin was 6.89 times higher than that of PVANPs, and 1.79 times higher than that of CS-NPs. By gavage of [ 99m Tc] isotope labeled Tat-CS-NPs in mini-pigs and single-photon emission computed tomography (SPECT) on pigs' gastrointestinal tract, it was further proved that the nanoparticles could reach colon and produce pharmacological effect. In conclusion, Tat-CS-NPs as vehicles for colon-specific drug delivery may be an efficient approach to improve oral bioavailability of protein and peptide drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation

et al. 2015

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pH and Reactive Oxygen Species‐Sequential Responsive Nano‐in‐Micro Composite for Targeted Therapy of Inflammatory Bowel Disease

Bertoni

Liu

Correia

et al. 2018

Adv Funct Materials

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Oxidative stress and abnormally high levels of reactive oxygen species (ROS) play an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD). Oxidation‐responsive nanoparticles (NPs) are formulated from a phenylboronic esters‐modified dextran (OxiDEX) that degrades selectively in response to hydrogen peroxide (H2O2). OxiDEX NPs are coated with chitosan and encapsulated in a pH‐sensitive polymer to produce nano‐in‐micro composites. The microparticles are spherical with homogeneous particle size (53 ± 3 µm) and maintain integrity at acidic pH, preventing the premature release of the NPs in gastric conditions. The degradation of NPs is highly responsive to the level of H2O2, and the release of the drug is sustained in the presence of physiologically relevant H2O2 concentrations. The presence of chitosan on the particles surface significantly enhances NPs stability in intestinal pH and their adhesion on the intestinal mucosa. Compared to a traditional enteric formulation, this formulation shows tenfold decreased drug permeability across C2BBe1/HT29‐MTX cell monolayer, implying that lower amount of drug would be absorbed to the blood stream and, therefore, limiting the undesired systemic side effects. Based on these results, a successful nano‐in‐micro composite for targeted therapy of IBD is obtained by combination of the responsiveness to pH and ROS.

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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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Oral colon delivery of insulin with the aid of functional adjuvants

Cited by 108 publications

References 193 publications

Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation

Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation

pH and Reactive Oxygen Species‐Sequential Responsive Nano‐in‐Micro Composite for Targeted Therapy of Inflammatory Bowel Disease

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

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