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New intranasal cross-linked mosapride xyloglucan pluronics micelles (MOS-XPMs) for reflux esophagitis disease: In-vitro optimization and improved therapeutic efficacy.

ABSTRACT: Mosapride belongs to class IV in Biopharmaceutics Classification System and is used in the treatment of reflux esophagitis. It exhibits poor bioavailability due to limited permeability, solubility and extensive first-pass metabolism. In this study, intranasal mosapride-loaded cross-linked xyloglucan Pluronic micelles (MOS-XPMs) was formulated and optimized to improve the low solubility & bioavailability of MOS. The solid dispersion technique using 23 full factorial design was applied. (MOS-XPMs) (F4) had the highest desirability value (0.952) and, therefore, it was selected as an optimal system. Xyloglucan cross-linked in the shell of Pluronic micelles offered improved stability and mucoadhesiveness to MOS-XPMs. 1H NMR spectra ensured the cross-linking of xyloglucan with Pluronic micelle shell and micelle stabilization. A Pharmacodynamic study revealed that MOS-XPMs showed 1.5-fold increase in duodenal and cecal motility compared to MOS suspension and 1.7-fold increase compared to the oral marketed product. The new MOS-XPMs were shown to be successful at improving the therapeutic efficacy of mosapride.

SUBMITTER: Hammad RW

PROVIDER: S-EPMC7025289 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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New intranasal cross-linked mosapride xyloglucan pluronics micelles (MOS-XPMs) for reflux esophagitis disease: <i>In-vitro</i> optimization and improved therapeutic efficacy.

Hammad Reham Waheed RW Sanad Rania Abdel-Basset RA Abdelmalak Nevine Shawky NS Torad Faisal A FA Latif Randa R

Journal of advanced research 20200128

Mosapride belongs to class IV in Biopharmaceutics Classification System and is used in the treatment of reflux esophagitis. It exhibits poor bioavailability due to limited permeability, solubility and extensive first-pass metabolism. In this study, intranasal mosapride-loaded cross-linked xyloglucan Pluronic micelles (MOS-XPMs) was formulated and optimized to improve the low solubility & bioavailability of MOS. The solid dispersion technique using 2<sup>3</sup> full factorial design was applied. ...[more]

PMID: 32089877

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Project description:Background and study aims ?Non-erosive reflux disease (NERD) includes minimal change esophagitis (MCE) and no endoscopic abnormalities. However, for most endoscopists, it is difficult to detect MCE with conventional white-light endoscopy (WLE). Linked color imaging (LCI) technology is the most recently developed image-enhancing technology and improves detection and differentiation of subtle mucosal changes using a color contrast method. This study assessed the efficacy of WLE combined with LCI for diagnosing MCE compared with WLE. Patients and methods ?Between February and May 2017, 44 NERD patients and 40 healthy subjects were enrolled in our study. First, the distal esophagus was examined using WLE followed by LCI. Second, three experienced endoscopists observed all the patients' white-light (WL) images and corresponding images of WL and LCI and then recorded presence or absence of minimal change esophagitis (MCE?+/-). The proportion of minimal change between the two groups was then compared. Third, five blinded endoscopists with different levels of endoscopic experience assessed whether MCE was present. Intraobserver reproducibility and interobserver agreement were described using the kappa value. Results ?The proportion of MCE in the NERD group (70.8?%, 35/48) was higher than that in the control group (22.5?%, 9/40, P ?<?0.001) when diagnosed by the three experienced endoscopists. Detection rates for MCE using WLE combined with LCI were higher than those using WLE (43/88, 48.9?% vs. 29/88, 33.0?%, P ?<?0.001). With WLE combined with LCI, intraobserver reproducibility signi?cantly improved, indicating that the combined approach can improve interobserver agreement compared with using WLE alone. Conclusions ?Endoscopic diagnosis of MCE using WLE combined with LCI images is effective. Intraobserver reproducibility and interobserver agreement in MCE can be improved when LCI is applied with conventional imaging (Clinical trial registration number: NCT03068572).

Project description:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Reflux oesophagitis is a common clinical disorder associated with significant morbidity. Proton pump inhibitors are the current pharmacotherapy of choice, but not all treated patients achieve symptom relief. Little is known about the efficacy of mosapride, a prokinetic agent which decreases episodes of gastro-oesophageal reflux, as an adjunct to proton pump inhibitors in improving the symptoms of reflux oesophagitis. WHAT THIS STUDY ADDS Mosapride was generally not more effective than placebo as an adjunct therapy to a standard dose of lansoprazole in decreasing the symptom burden of patients with reflux oesophagitis. However, in a subgroup with more severe symptoms, combination therapy with lansoprazole and mosapride was possibly superior to monotherapy with lansoprazole. AIMS To investigate if mosapride, a prokinetic agent, was an effective adjunct to acid suppression in improving the symptoms of reflux oesophagitis. METHODS Patients (n= 96) with reflux oesophagitis were randomly assigned to either mosapride (5 mg three times daily) or placebo for 4 weeks. Symptom severity was assessed by a validated questionnaire at enrolment, 4 and 8 weeks after medication. The primary outcome for the first 4 weeks was decrease in symptom scores. After a 3 day washout period, patients initially allocated to mosapride crossed over to placebo and vice versa for the next 4 weeks. The outcome of the second phase was maintenance of symptom control. All patients received lansoprazole (30 mg once daily) throughout study. RESULTS The decreased symptom score after 4 weeks of treatment with lansoprazole and mosapride (n= 50) was 13.42 +/- 1.16 (mean +/- SEM), similar to that of lansoprazole plus placebo (10.85 +/- 1.03, n= 46), with an insignificant difference of 2.57 (95% CI -0.53, 5.67, P= 0.103). However, a sub-group analysis for patients with pre-treatment scores of >18 points (n= 48) revealed that lansoprazole plus mosapride achieved a greater reduction of symptom score than lansoprazole plus placebo (18.22 +/- 1.91 vs. 12.88 +/- 1.65; mean difference of 5.34, 95% CI 0.28, 10.40, P= 0.039). In the second phase, there was no difference between lansoprazole with mosapride or placebo in maintaining symptom control (39/44 or 86.64% vs. 41/50 or 82%, P= 0.401). Subgroup analysis for those with substantial residual symptoms revealed similar results. CONCLUSION Compared with placebo, mosapride generally does not provide additional benefit to a standard dose of lansoprazole in patients with reflux oesophagitis, except possibly in the subgroup of severely symptomatic patients.

Project description:BackgroundDespite the high prevalence of gastroesophageal reflux disease (GERD), its risk factors are still a subject of controversy. This is probably due to inadequate distinction between reflux esophagitis (RE) and non-erosive reflux disease (NERD), and is also due to inadequate evaluation of adjacent stomach. Our aim is therefore to define background factors of RE and NERD independently, based on the evaluation of Helicobacter pylori infection and gastric atrophy.MethodsWe analyzed 10,837 healthy Japanese subjects (6,332 men and 4,505 women, aged 20-87 years) who underwent upper gastrointestinal endoscopy. RE was diagnosed as the presence of mucosal break, and NERD was diagnosed as the presence of heartburn and/or acid regurgitation in RE-free subjects. Using GERD-free subjects as control, background factors for RE and NERD were separately analyzed using logistic regression to evaluate standardized coefficients (SC), odds ratio (OR), and p-value.ResultsOf the 10,837 study subjects, we diagnosed 733 (6.8%) as RE and 1,722 (15.9%) as NERD. For RE, male gender (SC = 0.557, OR = 1.75), HP non-infection (SC = 0.552, OR = 1.74), higher pepsinogen I/II ratio (SC = 0.496, OR = 1.64), higher BMI (SC = 0.464, OR = 1.60), alcohol drinking (SC = 0.161, OR = 1.17), older age (SC = 0.148, OR = 1.16), and smoking (SC = 0.129, OR = 1.14) are positively correlated factors. For NERD, HP infection (SC = 0.106, OR = 1.11), female gender (SC = 0.099, OR = 1.10), younger age (SC = 0.099, OR = 1.10), higher pepsinogen I/II ratio (SC = 0.099, OR = 1.10), smoking (SC = 0.080, OR = 1.08), higher BMI (SC = 0.078, OR = 1.08), and alcohol drinking (SC = 0.076, OR = 1.08) are positively correlated factors. Prevalence of RE in subjects with chronic HP infection and successful HP eradication denotes significant difference (2.3% and 8.8%; p<0.0001), whereas that of NERD shows no difference (18.2% and 20.8%; p = 0.064).ConclusionsSignificantly associated factors of NERD are considerably different from those of RE, indicating that these two disorders are pathophysiologically distinct. Eradication of Helicobacter pylori may have disadvantageous effects on RE but not on NERD.

Dataset Information

New intranasal cross-linked mosapride xyloglucan pluronics micelles (MOS-XPMs) for reflux esophagitis disease: In-vitro optimization and improved therapeutic efficacy.

Publications

New intranasal cross-linked mosapride xyloglucan pluronics micelles (MOS-XPMs) for reflux esophagitis disease: <i>In-vitro</i> optimization and improved therapeutic efficacy.

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