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Barriers to the Int...
Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat
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- Lundquist, Patrik (author)
- Uppsala universitet,Institutionen för farmaci,Uppsala Univ, Sweden
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- Khodus, Georgiy (author)
- Uppsala universitet,Institutionen för farmaci,Uppsala Univ, Sweden
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- Niu, Zhigao (author)
- Univ Santiago Compostela, Spain
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- Thwala, Lungile Nomcebo (author)
- Univ Santiago Compostela, Spain; Louvain Drug Res Inst, Belgium
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- McCartney, Fiona (author)
- Univ Coll Dublin, Ireland
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- Simoff, Ivailo (author)
- Uppsala universitet,Institutionen för farmaci,Uppsala Univ, Sweden
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- Andersson, Ellen (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken ViN
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- Beloqui, Ana (author)
- Louvain Drug Res Inst, Belgium
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- Mabondzo, Aloise (author)
- CEA, France
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- Robla, Sandra (author)
- Univ Santiago Compostela, Spain
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- Webb, Dominic-Luc (author)
- Uppsala universitet,Gastroenterologi/hepatologi,Uppsala Univ, Sweden
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- Hellström, Per M., 1954- (author)
- Uppsala universitet,Gastroenterologi/hepatologi,Uppsala Univ, Sweden
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- Keita, Åsa (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten
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- Sima, Eduardo, Ph.D. 1975- (author)
- Uppsala universitet,Gastrointestinalkirurgi,Uppsala Univ, Sweden
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- Csaba, Noemi (author)
- Univ Santiago Compostela, Spain
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- Sundbom, Magnus (author)
- Uppsala universitet,Gastrointestinalkirurgi,Uppsala Univ, Sweden
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- Preat, Veronique (author)
- Louvain Drug Res Inst, Belgium
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- Brayden, David J (author)
- Univ Coll Dublin, Ireland
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- Alonso, Maria Jose (author)
- Univ Santiago Compostela, Spain
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- Artursson, Per (author)
- Uppsala universitet,Institutionen för farmaci,Uppsala Univ, Sweden
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(creator_code:org_t)
- 2022-08-23
- 2022
- English.
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:9, s. 14210-14229
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Abstract
Subject headings
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- Peptide drugs and biologics provide opportunities for treatments of many diseases. However, due to their poor stability and permeability in the gastrointestinal tract, the oral bioavailability of peptide drugs is negligible. Nanoparticle formulations have been proposed to circumvent these hurdles, but systemic exposure of orally administered peptide drugs has remained elusive. In this study, we investigated the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles displaying differing composition and surface characteristics, developed within the pan-European consortium TRANS-INT. The transport mechanisms and major barriers to nanoparticle permeability were investigated in freshly isolated human jejunal tissue. Cytokine release profiles and standard toxicity markers indicated that the nanoparticles were nontoxic. Three out of four nanoparticles displayed pronounced binding to the mucus layer and did not reach the epithelium. One nanoparticle composed of a mucus inert shell and cell-penetrating octarginine (ENCP), showed significant uptake by the intestinal epithelium corresponding to 28 ± 9% of the administered nanoparticle dose, as determined by super-resolution microscopy. Only a small fraction of nanoparticles taken up by epithelia went on to be transcytosed via a dynamin-dependent process. In situ studies in intact rat jejunal loops confirmed the results from human tissue regarding mucus binding, epithelial uptake, and negligible insulin bioavailability. In conclusion, while none of the four arginine-rich nanoparticles supported systemic insulin delivery, ENCP displayed a consistently high uptake along the intestinal villi. It is proposed that ENCP should be further investigated for local delivery of therapeutics to the intestinal mucosa.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- NATURVETENSKAP -- Kemi -- Annan kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Other Chemistry Topics (hsv//eng)
Keyword
- human
- insulin
- jejunum
- nanoparticle
- oral peptide delivery
- Medicinsk vetenskap
- Medical Science
Publication and Content Type
- ref (subject category)
- art (subject category)
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ACS Nano
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- By the author/editor
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Lundquist, Patri ...
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Khodus, Georgiy
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Niu, Zhigao
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Thwala, Lungile ...
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McCartney, Fiona
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Simoff, Ivailo
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show more...
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Andersson, Ellen
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Beloqui, Ana
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Mabondzo, Aloise
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Robla, Sandra
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Webb, Dominic-Lu ...
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Hellström, Per M ...
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Keita, Åsa
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Sima, Eduardo, P ...
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Csaba, Noemi
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Sundbom, Magnus
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Preat, Veronique
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Brayden, David J
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Alonso, Maria Jo ...
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Artursson, Per
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
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and Other Chemistry ...
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ACS Nano
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Uppsala University
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Linköping University