Measurement of intraluminal pH changes in the gastrointestinal tract of mice with gastrointestinal diseases

Sun, Yuanjie; Koyama, Yoshihisa; Shimada, Shoichi

doi:10.1016/j.bbrc.2022.06.061

Cited by 11 publications

(8 citation statements)

References 23 publications

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“…and in mice with colitis a pH of 6.7 (45). The lower value in colitis than the normal mice was consistent with reports in the human IBD (46), although the degree of acidity may vary depending on disease severity.…”

Section: Discussionsupporting

confidence: 90%

“…Additionally, PNIPAM-MAA is not only thermo-responsive but also pH-responsive. The measurement of the colon content in normal mice showed a pH of 7.8 and in mice with colitis a pH of 6.7 ( 45 ). The lower value in colitis than the normal mice was consistent with reports in the human IBD ( 46 ), although the degree of acidity may vary depending on disease severity.…”

Section: Discussionmentioning

confidence: 99%

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Thermo-Responsive Polymers Targeting Inflammation in Murine Colitis

Zhang,

Jin,

Tang

et al. 2023

Preprint

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Targeting the site of inflammation is an ideal approach for treating inflammatory bowel disease (IBD). Inflammation targeting enables maximal drug-on-target effects while minimizing off-target side effects. Negatively charged drug carriers have been shown to facilitate drug delivery to inflamed colon mucosa after local administration. To modulate the negative charges and integrate responsiveness to stimuli, here we describe thermo-responsive, inflammation-targeting (TRIT) hydrogels based on functionalized poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-MAA). We show that both chemical modification types and polymer molecular weights affect the resultant microgels’ adhesion to the inflamed colon in dextran sulfate sodium (DSS)-induced murine colitisin vivo. Further, we quantified the correlations between microgels’ adhesion and colitis severity for individual mice, demonstrating that the microgels’ adhesion correlated directly with weight loss percentage in DSS-treated mice. By exploiting charge-mediated interaction and thermo-responsiveness, TRIT hydrogels represent a promising strategy to target inflamed colon mucosa as a drug delivery platform for colonic IBD treatment.TeaserThis study developed thermo-responsive, inflammation-targeting (TRIT) hydrogels that harness charge-mediated interaction and sol-to-gel transition to target inflamed colon mucosa as a new approach for treating inflammatory bowel disease.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Thermo-Responsive Polymers Targeting Inflammation in Murine Colitis

Zhang,

Jin,

Tang

et al. 2023

Preprint

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“…This problem may be pronounced for weakly basic drugs with low solubility at high pH, especially those with a narrow therapeutic index, or requiring prolonged release, because in the lower GIT the pH is >6.8 [ 1 ]. Furthermore, food intake, disease state (e.g., inflammatory bowel disease, gastritis, colitis), concomitant medication (e.g., proton pump inhibitors), and inter- and intra-individual variations, among other factors, can alter the pH in the GIT, which deviates from the pH of simulated gastric and intestinal fluid for in vitro testing and prediction [ 2 , 3 , 4 ]. Hence, novel strategies to formulate weakly basic drugs with extreme pH-dependent solubility in controlled release forms could enhance the repertoire of advanced medications available to patients.…”

Section: Introductionmentioning

confidence: 99%

Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery

et al. 2023

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Bioavailability of weakly basic drugs may be disrupted by dramatic pH changes or unexpected pH alterations in the gastrointestinal tract. Conventional organic acids or enteric coating polymers cannot address this problem adequately because they leach out or dissolve prematurely, especially during controlled release applications. Thus, a non-leachable, multifunctional terpolymer nanoparticle (TPN) made of cross-linked poly(methacrylic acid) (PMAA)-polysorbate 80-grafted-starch (PMAA-PS 80-g-St) was proposed to provide pH transition-independent release of a weakly basic drug, verapamil HCl (VER), by a rationally designed bilayer-coated controlled release bead formulation. The pH-responsive PMAA and cross-linker content in the TPN was first optimized to achieve the largest possible increase in medium uptake alongside the smallest decrease in drug release rate at pH 6.8, relative to pH 1.2. Such TPNs maintained an acidic microenvironmental pH (pHm) when loaded in ethylcellulose (EC) films, as measured using pH-indicating dyes. Further studies of formulations revealed that with the 1:2 VER:TPN ratio and 19% coating weight gain, bilayer-coated beads maintained a constant release rate over the pH transition and exhibited extended release up to 18 h. These results demonstrated that the multifunctional TPN as a pHm modifier and pH-dependent pore former could overcome the severe pH-dependent solubility of weakly basic drugs.

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“…However, on the way to the rectum, the pH increases again to between 7.0 and 8.0, resulting in an alkaline environment. 34,35 Nonetheless, the pH values of different parts of the intestine may vary among individuals, particularly the colon. Various factors, such as mucosal bicarbonate and lactate production, carbohydrates fermented by bacteria, short-chain fatty acids absorption in the mucosa, and intestinal transport, influence the luminal pH of the colon.…”

Section: Phmentioning

confidence: 99%

“…Although fluctuations in colon pH have been observed, the overall trend of pH changes is towards increased acidity. 35,37 Therefore, designing oral nanomedicine systems for IBD should make the most of the changes in gastrointestinal pH and the fluctuations in inflamed gastrointestinal pH to select suitable nanoparticle materials.…”

Section: Phmentioning

confidence: 99%