TY - JOUR

T1 - Effects of prophylactic antibiotics administration on barrier properties of intestinal mucosa and mucus from preterm born piglets

AU - Mortensen, Janni Støvring

AU - Nguyen, Duc Ninh

AU - Mørck Nielsen, Hanne

AU - Harloff-Helleberg, Stine

N1 - Funding Information: The Department of Veterinary and Animal Sciences and the Department of Experimental Medicine at the University of Copenhagen are greatly acknowledged for providing piglet and pig intestines, respectively. Scholar students Sylvester Petersen and Adrian Gjetnes Rossebø (Department of Pharmacy, University of Copenhagen) are acknowledged for their help with mucus isolation. Postdoc René Liang is acknowledged for valuable input on current clinical practice for NEC treatments and prophylactic antibiotics treatments. The Franz diffusion cells were funded by the Drug Research Academy (University of Copenhagen). Funding Information: This work was supported by Novo Nordisk Foundation (Grand Challenge Program; NNF16OC0021948) and the Lundbeck Foundation (grant no. R303-2018-2968).

PY - 2023

Y1 - 2023

N2 - Early intervention and short-duration treatments with antibiotics in premature infants are reported to reduce the incidence of necrotizing enterocolitis (NEC), a terrible disease with severe inflammation and impaired intestinal barrier properties. Yet, it is unclear how antibiotics exposure, as well as route of administration used for dosing, can minimize the risk of NEC. With this study, we aimed to investigate if and how administration of antibiotics may affect the barrier properties of intestinal mucosa and mucus. We compared how parenteral (PAR) and a combination of enteral and parenteral (ENT+PAR) ampicillin and gentamicin given to preterm born piglets within 48 h after birth affected both barrier and physical properties of ex vivo small intestinal mucosa and mucus. Permeation of the markers mannitol, metoprolol, and fluorescein-isothiocyanate dextran of 4 kDa (FD4) and 70 kDa (FD70) through the mucosa and mucus was evaluated. For all markers, permeation through the mucosa and mucus collected from PAR piglets tended to be reduced when compared to that observed using untreated piglets. In contrast, permeation through the mucosa and mucus collected from ENT+PAR piglets tended to be similar to that observed for untreated piglets. Additionally, rheological measurements on the mucus from PAR piglets and ENT+PAR piglets displayed a decreased Gʹ and Gʹ/Gʺ ratio and decreased viscosity at 0.4 s−1 as well as lower stress stability compared to the mucus from untreated piglets. Graphical Abstract: [Figure not available: see fulltext.].

AB - Early intervention and short-duration treatments with antibiotics in premature infants are reported to reduce the incidence of necrotizing enterocolitis (NEC), a terrible disease with severe inflammation and impaired intestinal barrier properties. Yet, it is unclear how antibiotics exposure, as well as route of administration used for dosing, can minimize the risk of NEC. With this study, we aimed to investigate if and how administration of antibiotics may affect the barrier properties of intestinal mucosa and mucus. We compared how parenteral (PAR) and a combination of enteral and parenteral (ENT+PAR) ampicillin and gentamicin given to preterm born piglets within 48 h after birth affected both barrier and physical properties of ex vivo small intestinal mucosa and mucus. Permeation of the markers mannitol, metoprolol, and fluorescein-isothiocyanate dextran of 4 kDa (FD4) and 70 kDa (FD70) through the mucosa and mucus was evaluated. For all markers, permeation through the mucosa and mucus collected from PAR piglets tended to be reduced when compared to that observed using untreated piglets. In contrast, permeation through the mucosa and mucus collected from ENT+PAR piglets tended to be similar to that observed for untreated piglets. Additionally, rheological measurements on the mucus from PAR piglets and ENT+PAR piglets displayed a decreased Gʹ and Gʹ/Gʺ ratio and decreased viscosity at 0.4 s−1 as well as lower stress stability compared to the mucus from untreated piglets. Graphical Abstract: [Figure not available: see fulltext.].

KW - Administration routes

KW - Ampicillin

KW - Gentamicin

KW - Mucus elasticity and viscosity

KW - Permeability barrier

U2 - 10.1007/s13346-023-01309-8

DO - 10.1007/s13346-023-01309-8

M3 - Journal article

C2 - 36884193

AN - SCOPUS:85149482544

VL - 13

SP - 1456

EP - 1469

JO - Drug Delivery and Translational Research

JF - Drug Delivery and Translational Research

SN - 2190-393X

ER -