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Barriers to the Int...
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Lundquist, PatrikUppsala universitet,Institutionen för farmaci,Uppsala Univ, Sweden
(author)
Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-08-23
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American Chemical Society (ACS),2022
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-483089
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-483089URI
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https://doi.org/10.1021/acsnano.2c04330DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-188448URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding Agencies|European TRANS-INT Consortium; European Union [281035]; TRANS-INT; Swedish Research Council [2822, 2020-01586]; FRS-FNRS (Fonds de la Recherche Scientifique) , Belgium; Competitive Reference Groups, Conselleria de Educacion e Ordenacion Universitaria, Xunta de Galicia [ED431C 2021/17]; European Commission, Education, Audiovisual and Culture Executive Agency (EACEA) [20120028]; Swedish Government, Sweden
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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 and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Khodus, GeorgiyUppsala universitet,Institutionen för farmaci,Uppsala Univ, Sweden
(author)
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Niu, ZhigaoUniv Santiago Compostela, Spain
(author)
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Thwala, Lungile NomceboUniv Santiago Compostela, Spain; Louvain Drug Res Inst, Belgium
(author)
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McCartney, FionaUniv Coll Dublin, Ireland
(author)
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Simoff, IvailoUppsala universitet,Institutionen för farmaci,Uppsala Univ, Sweden(Swepub:uu)ivasi192
(author)
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Andersson, EllenLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken ViN(Swepub:liu)ellan64
(author)
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Beloqui, AnaLouvain Drug Res Inst, Belgium
(author)
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Mabondzo, AloiseCEA, France
(author)
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Robla, SandraUniv Santiago Compostela, Spain
(author)
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Webb, Dominic-LucUppsala universitet,Gastroenterologi/hepatologi,Uppsala Univ, Sweden(Swepub:uu)domwe127
(author)
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Hellström, Per M.,1954-Uppsala universitet,Gastroenterologi/hepatologi,Uppsala Univ, Sweden(Swepub:uu)perhe742
(author)
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Keita, ÅsaLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten(Swepub:liu)asave24
(author)
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Sima, Eduardo,Ph.D.1975-Uppsala universitet,Gastrointestinalkirurgi,Uppsala Univ, Sweden(Swepub:uu)edusi537
(author)
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Csaba, NoemiUniv Santiago Compostela, Spain
(author)
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Sundbom, MagnusUppsala universitet,Gastrointestinalkirurgi,Uppsala Univ, Sweden(Swepub:uu)magsundb
(author)
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Preat, VeroniqueLouvain Drug Res Inst, Belgium
(author)
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Brayden, David JUniv Coll Dublin, Ireland
(author)
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Alonso, Maria JoseUniv Santiago Compostela, Spain
(author)
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Artursson, PerUppsala universitet,Institutionen för farmaci,Uppsala Univ, Sweden(Swepub:uu)perartur
(author)
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Uppsala universitetInstitutionen för farmaci
(creator_code:org_t)
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In:ACS Nano: American Chemical Society (ACS)16:9, s. 14210-142291936-08511936-086X
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Khodus, Georgiy
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McCartney, Fiona
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Andersson, Ellen
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Beloqui, Ana
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Mabondzo, Aloise
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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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