Oral Formulations Research Articles

GLP-1 RA-Semaglutide a game changer drug for management of obesity with and without Diabetes - A narrative review

Obesity is a chronic and relapsing disease marked by excessive fat accumulation that poses serious health risks, with an increasing global prevalence including in low- and middle-income countries. Obesity-related complications, including cardiovascular diseases, diabetes, and cancer, also contribute to significant healthcare costs. Management strategies involve lifestyle modifications, pharmacological interventions, and, in severe cases, surgical procedures. Semaglutide, a GLP-1 receptor agonist, has emerged as an effective treatment for both obesity and type 2 diabetes, showing significant weight loss outcomes and improvements in metabolic health across various patient groups. However, careful monitoring of adverse effects and drug interactions is crucial for optimizing therapeutic outcomes.Several novel agents are under development, with multi-hormone receptor agonists and oral formulations likely to become available in the coming years. As effective treatment options expand, cost and availability will need to be addressed to enable equitable access to treatment. Bangladesh J Medicine 2024; 35: 133-146

Pioneering Oral Insulin Formulations and Delivery Techniques: A Review

The development of oral insulin presents significant promise for diabetes treatment, mitigating peripheral hyperinsulinemia, weight gain, and hypoglycemia while enhancing patient convenience and facilitating rapid insulinization of the liver. Effective oral insulin products are crucial for early intensive insulin therapy, which ensures tight glycaemic control and delays diabetes complications. However, despite the need, oral insulin has faced many challenges, and past technologies have had limited success. Repeated insulin injections can result in local hypertrophy over time generating attention to user-friendly oral insulin delivery systems that are not invasive to the body and copy the natural pathway. This review article examines New methods for oral insulin delivery that have shown promise, using techniques like complexation, hydrogels, and nanoparticles to boost effectiveness, though they still trail injectable insulin. Further studies will help determine how well oral insulin works at various doses and inform the development of competing formulations.

Characterization of extracted alpha cellulose from Manihot esculenta (cassava) peels as formulation aid for paracetamol tablet

Background: Alpha-cellulose as a pharmaceutical excipient can be employed as a binding agent in tablet formulation. Cassava peels husk are waste agricultural material and is being investigated for its α-cellulose for use in oral solid pharmaceutical formulation. Purpose: The objective of this study is to extract α-cellulose from cassava peels agro-industrial waste using a standard method, subject the extracted cassava peels cellulose and determine its phytochemical and physicochemical properties of formulated granules of paracetamol. Methods: Alpha-cellulose from cassava peel was extracted using alkali method. The fresh peels were prepared, milled into slurry and de-watered to obtain a coarse wet material, dried, milled and sieved to obtain very fine powdered particles. Phytochemical analysis and characterization of extracted α-cellulose powder were determined. Differential scanning calorimetry (DSC), scanning electron micrographs (SEM), and x-ray diffractogram (XRD) analysis of extracted cassava peel cellulose were done. Paracetamol granules was prepared by wet granulation using varying concentrations of the binders. Results: DSC and XRD results revealed a semi-crystalline material with amorphous and crystalline regions. while the SEM showed a lumpy structure and reticular shape. Pre-compression evaluations of the formulated batches of paracetamol granules showed that cassava peels cellulose (CPC) have similar flow properties with those of microcrystalline cellulose BP (MCC) and acacia BP (ACA) powders respectively. The granules have free flow properties with average angles of repose (CPC ≤ 27.60 MCC < 26.90 and ACA ≤ 25.60), compressibility index (CPC ≤ 25, MCC ≤ 23 and ACA ≤ 21.7%), Hausner’s ratio (CPC ≤ 1.32, MCC ≤ 1.31, and ACA ≤ 1.27) respectively. Conclusion: The extracted cassava peel α-cellulose was found ideal as pharmaceutical excipient binder in oral solid dosage forms.

Novel approaches in Paediatric Drug Delivery System

The development of medication delivery technology has led to an increase in the popularity of pediatric formulations. However, there is absence of secure and efficient drug delivery mechanism for pediatric patients. It is crucial to design and create a novel and suitable delivery system to guarantee precise and reliable medication administration to pediatric patients, as their pharmacokinetics and pathophysiologic profiles differ from those of adults. Under this heading, discussion will be carried out in order to increase stability; new medication delivery techniques and technology are being developed to enhance the stability, toxicity, flexibility, moreover secure aspects of pediatric oral formulations. Specifically, issues with patient acceptability and manufacturability are discussed in this section, and innovative medication delivery methods are examined to address current issues.

Cost-effectiveness of MLC601 in post-stroke functional recovery compared with placebo - the CHIMES & CHIMES-E studies

BackgroundDespite progress in stroke therapy (e.g., revascularisation interventions by thrombolysis and/or thrombectomy, organised stroke care), many stroke survivors will have impairment of neurological function. We aimed to compare the cost-effectiveness of an oral natural formulation, MLC601, versus placebo in functional recovery among subjects receiving standard of care after an ischemic stroke of intermediate severity assessed with NIH Stroke Scale at baseline (b-NIHSS 8–14).MethodsA Markov cohort model with a 2-year time horizon was developed to simulate patients from a published randomised placebo-controlled clinical trial of MLC601 in their post-stroke functional recovery assessed by modified Rankin Score (mRS), from a health system perspective. Transition probabilities were derived from a multi-centre clinical trial in South East Asia. As cost and utility data were not collected in the trial, therefore we extracted them from the published literature. The main outcomes were incremental cost, incremental quality-adjusted life-year (QALY) gained, and incremental cost-effectiveness ratio (ICER). Besides base-case and sensitivity analyses, we performed subgroup analyses to explore the heterogeneity of patients with poor-prognosis factors (b-NIHSS 10–14, stroke onset to treatment time > 48 h, rehabilitation during first 3 month). All costs are expressed in 2022 Euro and USD, with an annual discount rate of 3% applied to costs and QALYs.ResultsBase-case analysis showed that MLC601 was cost-effective compared with placebo, with €5,080 saved and 0.45 QALY gained, resulting in an ICER of -€11,352.50 per QALY gained. Similarly, results from subgroup analyses indicated that the use of MLC601 was a dominant strategy in all subgroups with poor-prognosis factors. Sensitivity analyses revealed the results were robust.ConclusionCompared with placebo on top of standard stroke care, MLC601 was cost-effective in post-stroke functional recovery over two years. Due to the lack of cost and utility data from the study population, the results might not be generalizable to other settings. Further studies with country-specific data are needed to confirm the results of this study.Trial registrationURL http://www.clinicaltrials.gov. Unique identifier NCT00554723 November 7, 2007.

Usage of Antifungal Agents in Pediatric Patients Versus Adults: Knowledge and Gaps.

Invasive fungal infections (IFIs) present significant challenges in managing hospitalized and immunocompromised pediatric patients, contributing to high morbidity and mortality. Despite advancements in diagnostics and treatment, outcomes remain suboptimal due to unique clinical epidemiology, lack of pediatric-specific trials, and varied pharmacokinetics. The emergence of new antifungal classes and agents has expanded our options for preventing and treating IFIs in children, enhancing the safety and effectiveness of antifungal therapy. The oral formulations of ibrexafungerp, fosmanogepix and olorofim along with the extended dosing intervals of rezafungin show promising features for effective antifungal treatment in pediatrics. Despite the promising potential of novel antifungal drugs, their performance in heavily immunosuppressed patients remains unstudied. Until then, dedicated antifungal stewardship programs for high-risk patients are essential to optimize therapeutic outcomes, improve patient care, and limit the emergence of resistance.

Comparison of oven drying and freeze drying methods for the production of fast melt films containing quetiapine fumarate

Background Quetiapine fumarate (QTP) is commonly prescribed for schizophrenic patient, typically available in tablet or oral suspension form, presenting challenges such as administration difficulties, fear of choking and distaste for its bitter taste. Fast melt films (FMF) offer an alternative dosage form with a simple development process, ease of administration and rapid drug absorption and action onset. Objective This study aims to prepare FMF with different formulations using solvent casting methods and to compare the effects of different drying methods, including oven drying and freeze drying, on the properties of the films. Methods Various formulations were created by manipulating polymer types (starch, hydroxypropyl methylcellulose (HPMC) and guar gum) at different concentrations, along with fixed concentrations of QTP and other excipients. Characterisation tests including surface morphology, weight, thickness, pH, tensile strength, elongation length, Young’s modulus, folding endurance and disintegration time were conducted. The optimal FMF formulation was identified and further evaluated for moisture and drug content, dissolution behaviour, accelerated stability, X-ray diffraction (XRD), and palatability. Results FMF containing 10 mg guar gum/film developed using oven drying emerged as the optimum choice, exhibiting desirable film appearance, ultra-thin thickness (0.453 ± 0.002 mm), appropriate pH for oral intake (pH 5.0), optimal moisture content of 11.810%, rapid disintegration (52.67 ± 1.53 seconds), high flexibility (folding endurance > 300 times) and lower Young’s modulus (1.308 ± 0.214). Conclusion Oven drying method has been proven to be favourable for developing FMF containing QTP, meeting all testing criteria and providing an alternative option for QTP prescription.

Development and Optimization of Gellan Gum-Based Gastro-Retentive Microbeads for Enhanced Controlled Release of Acyclovir.

Modified release systems offer enhanced spatial and temporal control over drug delivery, leading to better blood plasma profiles, targeted therapy, reduced side effects, and improved patient compliance. Recent advancements focus on using biocompatible polymers to achieve sustained or controlled drug release, particularly for gastroretentive systems that enhance oral bioavailability and minimize dose-dependent toxicity. This study explores the formulation of floating microbeads of acyclovir (ACV) using various hydrophilic polymers. The prototype oral formulations demonstrated superior micrometric properties, including bulk density, tapped density, Carr’s index, Hausner’s ratio, angle of repose, average particle size, yield, and drug content. In-vitro dissolution studies revealed controlled release characteristics, with optimal floating time and entrapment efficiency achieved using specific concentrations of olive oil and polymers. Drug release trailed the Korsmeyer-Peppas model, indicating a diffusioncontrolled mechanism. The formulations exhibited good storage stability, in-vivo floating ability, and higher bioavailability in rabbits compared to ACV solutions. The results suggest that hydrophilic polymers are effective for formulating floating microbeads with controlled release and reproducible profiles.

Bioequivalence of two oral formulations of nitazoxanide in healthy volunteers

Objective: This study evaluated the bioequivalence (BE) between two Nitazoxanide 20mg/ml oral suspension formulations. Methods: We carried out a single-center, open-label, randomized, single-dose, two-sequence, two-period. Subjects received single oral doses of 500 mg Nitazoxanide oral suspension. Whole blood samples were collected pre-dose and at specified intervals up to 12 h post-dose to assess pharmacokinetic parameters. Results: Thirty healthy adult subjects completed the study. We found the 90% confidence intervals for the geometric mean ratios for the Tixozanide area under the curve AUC0‐t and AUC0‐∞ and maximum plasma concentration (Cmax) were within the established limits of 80% to 125 % of BE. Conclusion: The criteria for BE were met for the nitazoxanide formulations from Eurofarma Laboratórios S.A.

Türkçenin Yabancı Dil Olarak Öğretiminde Okuma Metinlerinin Kültür Aktarımında Kullanımı ve Metin İşleme Sürecine Uygunluğu

In foreign language teaching, not only grammar but also cultural teaching should be targeted. It is important that the selected texts facilitate both language learning and cultural learning and make students love language teaching. In order to teach Turkish and Turkish culture, students should read texts that describe Turkish culture and convey the cultural elements in these texts to others in written and oral form, which allows them to know and embrace these cultural elements. The texts used should include cultural elements and should be aimed at teaching Turkish culture to students. Reading texts that accurately convey Turkish culture should be included in teaching Turkish to foreigners. Because each language is taught within its own logic. The purpose of this research is to address the importance and necessity of using texts for cultural transfer. In this direction, a case study was conducted within the framework of qualitative research and the research was presented. In the formation of the research, the texts named Wedding in Anatolia, Turkish Bracelets, Sultan Ahmet Mosque and Hagia Sophia were selected and examined in terms of cultural transfer during the teaching of Turkish to foreigners. As a result of the research, it was determined that students who read the selected texts and learn Turkish as a foreign language will be introduced to Turkish culture, customs and traditions. Key words: Teaching Turkish as a foreign language, Turkish language, text usage, cultural transfer, achievements, processing of text process

Teacher Strategies in Implementing Guidance Counseling To Improve Students' Morals

This research aims to determine teachers' strategies in implementing guidance and counseling to instill morals in students. This research uses a qualitative method in which data collection is carried out through observation, in-depth interviews, and analysis of written documentation. Meanwhile, the data was analyzed using a thematic approach to find themes in the data collected in the field. The research results show that the teacher's strategy in implementing counseling guidance to instill student morals has been carried out well through several methods that the school has determined. Teacher strategies in implementing counseling guidance include oral form. The second strategy is counseling guidance in the form of practice. The results of this research also show that the supporting factors in cultivating students' morals at the Alkahiraat Senior Islamic High School are the family environment and infrastructure, and the inhibiting factors are the lack of support and attention from parents and the influence of peer environment. Suggestions for students at the Alkhairaat Alkahiraat Islamic Junior High School Palu are that they always be aware of their responsibilities as servants, obey the commands of Allah SWT, and stay away from his prohibitions. This will create students with noble morals, as we all hope for, according to the teachings of the Al-Qur'an and Hadith.

Advancing the Harmonization of Biopredictive Methodologies through the Product Quality Research Institute (PQRI) Consortium: Biopredictive Dissolution of Dipyridamole Tablets.

Biorelevant dissolution and its concept have been widely accepted and further developed to meaningfully predict the bioperformance of oral drug products. Biorelevant methodologies have been applied to design and optimize oral formulations, to facilitate formulation bridging, and to predict the outcome of bioperformance by coupling the results with modeling. Yet, those methodologies have often been independently customized to align with specific aspects of the oral drug products being developed. Therefore, the evolution of biorelevant dissolution methodologies has taken slightly diverse pathways rather than being standardized like compendial quality control (QC) methodologies. This manuscript presents an effort through the Product Quality Research Institute (PQRI, https://pqri.org) consortium entitled: the standardization of "in vivo predictive dissolution methodologies and in silico bioequivalent study working group" to find the key parameters for biorelevant dissolution, to identify the best practices, and to move toward standardization of biorelevant dissolution methodologies. This working group is composed of members from 10 pharmaceutical companies and academic institutes. The consortium project will be accomplished in five phases, whereby the first two phases have already been completed and published. In this paper, the next two phases are addressed by reporting the biorelevant dissolution profiles of dipyridamole, a weak base model drug, then incorporating the dissolution results into physiologically based biopharmaceutics modeling (PBBM) to determine whether they would lead to bioequivalence (BE) or non-BE.

Newer formulations of oral testosterone undecanoate: development and liver side effects.

Testosterone deficiency is a clinical disorder due to either failure of the testes to produce testosterone or failure of the hypothalamus or pituitary to produce sufficient gonadotropins. Previous formulations of oral testosterone therapy, particularly methyltestosterone, have been associated with adverse liver effects. Many different routes of testosterone delivery have been developed, each with their own administrative benefits and challenges. Newer formulations of oral testosterone undecanoate (TU) provide a convenient administration option, although their use has been limited by hepatotoxicity concerns based on older methyltestosterone data, and prescribing physicians may still be concerned about adverse liver effects. In this review, we discuss the history of oral testosterone development, clarify the mechanism of action of oral TU, and describe the relevant liver safety findings. Relevant literature was allocated to present a review on the history of oral TU development and the mechanism of action of oral TU. We pooled data from individual studies of oral TU products to present a safety summary. Overall, safety results from studies of the newer formulations of oral TU showed that increased liver function test values are not generally associated with oral TU formulations and that no clinically significant liver toxicities were noted in clinical trials of oral TU. Continued research into the safety of oral TU will contribute to a better understanding of the potential risks in patients receiving this therapy, an outcome that highlights the importance of providing patient education and reassurance regarding oral TU safety.

Pricing dynamics of anti-seizure medications in the U.S.

BackgroundThe median cost of anti-seizure medications (ASM) in the United States (U.S.) nearly doubled per person between 2006 and 2021. This increase, combined with shifts in ASM usage and the impact of the COVID-19 pandemic on drug supply chains amid rising inflation, underscored the urgent need to scrutinize ASM pricing dynamics. This study aimed to analyze the complex dynamics of ASM pricing in the U.S. over the past decade (2013–2023); this included how the entry of generic ASMs influenced the pricing of brand-name counterparts and what impacted price variations across different ASM formulations (e.g., significant inflation, the COVID-19 pandemic). MethodsThis study utilized National Average Drug Acquisition Cost (NADAC) data from November 2013 to July 2023. We adjusted ASM prices for inflation using the Consumer Price Index for Medicinal Drugs - Seasonally Adjusted (CPI-MDS). Statistical analyses included fixed effects regressions and multivariable regression analysis to evaluate the impact of inflation, the number of medication labelers, and the COVID-19 pandemic on ASM prices. ResultsOur study analyzed 23 ASMs approved by the U.S. Food and Drug Administration (FDA), which encompassed 223 oral formulations:112 brand-name and 111 generics. From 2013–2016 to 2020–2023, accounting for standard deviations (SD), the average price of brand-name ASMs increased from $8.71 (SD 5.9) to $15.43 (SD 10.7), while generic ASMs saw a slight decrease from $1.39 (SD 1.8) to $1.26 (SD 1.6). Consequently, the price gap between brand-name and generic ASMs surged from 1452.39 % to 3399.26 %. The proportion of matched brand-name and generic ASMs with a price difference of 1000 %–9999 % increased from 32.88 % (2013–2016) to 41.43 % (2020–2023), while those exceeding 10,000 % rose from 16.44 % to 20 % in the same period. Generic immediate-release (IR) formulations were significantly less expensive than extended-release (ER) or delayed-release (DR) counterparts, with cost differences reaching up to 7751.20 %. The number of medication labelers was inversely related to generic ASM prices, which decreased by 5.45 % (p = 0.001) with each additional generic labeler, while brand-name ASM prices increased by 2.46 % (p < 0.001) with each additional generic labeler. The COVID-19 pandemic led to a 24.4 % increase in brand-name ASM prices and a 23.1 % decrease in generic ASM prices. ConclusionsThe findings reveal an expanding price disparity between brand-name and generic oral ASMs. An inverse relationship was observed between the number of medication labelers and generic ASM prices, with additional labelers driving down generic prices. However, introducing more generic labelers led to a significant increase in brand-name ASM prices. Furthermore, following patent expirations, brand-name ASM prices rose—a trend explained by the "generics paradox," where, contrary to expectations, brand prices do not decrease and may even increase when generics enter the market. These findings underscore the need for targeted interventions in drug pricing policies to manage the rising costs associated with epilepsy treatment. To ensure equitable access to ASMs, stakeholders must understand and address the factors driving these pricing dynamics.

A Multi-Institutional, Retrospective, Observational Study on Administration Status and Safety of In-Hospital Oral Selenium Preparation in Pediatric Patients Predominantly Suffering from Gastrointestinal Disease.

Selenium deficiency in patients with gastrointestinal diseases treated with long-term central venous nutrition is a clinical problem. Only injectable selenium is approved in Japan, and oral selenium preparations are prepared in hospitals from reagents, but their efficacy and safety are unknown. We conducted a retrospective study investigating the relationship between selenium administration and oral selenium formulations and adverse events. In this study, 239 selenium-treated cases and 220 selenium-untreated cases adjusted for patient background were selected as a reference group. The median (interquartile range, IQR) age was 1.3 (0.4-4.4) and 1.3 (0.3-4.5) years, respectively; gastrointestinal diseases were most common in 110 (46.0%) and 104 (47.3%) cases. The median (IQR) duration of treatment or observation with oral selenium was 446 (128-1157) and 414 (141-1064) days, respectively. The median (IQR) dose per body weight at the maintenance dose was 2.6 (1.7-3.9) μg/kg, and the median (IQR) serum selenium concentration at the maintenance dose was 8.5 (7.0-10.6) μg/mL within the upper tolerated dose limit and approximately the reference range. There was no difference in selenium dose, serum selenium concentration, or serum-selenium-concentration-to-dose ratio (C/D ratio) for adverse events. The incidence of adverse events was compared with that of patients not treated with selenium. An oral selenium preparation administered below the upper tolerated dose limit can be used effectively and safely in pediatric patients.

Micronization of ciprofloxacin by the Supercritical Antisolvent (SAS) Technique

Ciprofloxacin is a broad-spectrum antibiotic that is proposed for pulmonary administration. In this work micronization of ciprofloxacin was performed by the Supercritical Antisolvent Technique (SAS) using ciprofloxacin base (CIP) in ethanol/acetic acid and ciprofloxacin hydrochloride salt (CIP·HCl) in methanol at 40–60 ºC and 100–150 bar. Yields ranged from 40 % to 90 %. CIP precipitated incorporating acetate whilst CIP·HCl precipitated as the AH1 anhydrous form. CIP and CIP·HCl particles exhibited an acicular morphology (0.2–0.9 μm wide × 1–4 μm long). Micronization adding lactose, PVP K-10 and K-30 modified the precipitate morphology. CIP·HCl:lactose and CIP·HCl:PVP K-30 at a 4:1 drug:excipient mass ratio precipitated like flakes. CIP·HCl:PVP K-10 precipitated as submicron globular particles suitable for oral formulation. Increasing the PVP content, the morphology changed to sheets and flakes, which could be used for pulmonary administration. The antibacterial activity of the samples for Staphylococcus epidermidis was confirmed.

Pharmacokinetics and Plasma Protein Binding of Flunixin in Rainbow Trout (Oncorhynchus mykiss).

Flunixin's pharmacokinetics, bioavailability, and plasma protein binding were examined in rainbow trout. The experiment involved 252 rainbow trout (Oncorhynchus mykiss) maintained at 12 ± 0.6°C. Flunixin was administered to rainbow trout via intravascular (IV), intramuscular (IM), and oral routes at a dosage of 2.2 mg/kg. Plasma samples were collected at times 0 (control), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 h. High-pressure liquid chromatography-ultraviolet was employed to quantify flunixin concentrations. The elimination half-life (t1/2ʎz) for flunixin was 8.37 h for IV, 8.68 h for IM, and 8.76 h for oral. The t1/2ʎz was similar between administration groups. The volume of distribution at a steady state and total body clearance were 55.81 mL/kg and 6.83 mL/h/kg, respectively, after IV administration. The mean peak plasma concentration was 6.24 ± 0.41 μg/mL at 4 h for oral administration and 13.98 ± 0.86 μg/mL at 2 h for IM administration. The invitro protein binding ratio of flunixin in rainbow trout plasma was 96.34 ± 2.29%. The bioavailability of flunixin after oral (25.74%) administration was lower than that after IM (66.70%) administration. Thus, developing an oral pharmaceutical formulation that can be administered with feed and has high bioavailability could enhance the therapeutic effect.

Microbiome- and Host Inflammasome-Targeting Inhibitor Nanoligomers Are Therapeutic in the Murine Colitis Model.

Autoimmune and autoinflammatory diseases account for more than 80 chronic conditions affecting more than 24 million people in the US. Among these autoinflammatory diseases, noninfectious chronic inflammation of the gastrointestinal (GI) tract causes inflammatory bowel diseases (IBDs), primarily Crohn's and ulcerative colitis (UC). IBD is a complex disease, and one hypothesis is that these are either caused or worsened by compounds produced by bacteria in the gut. While traditional approaches have focused on pan immunosuppressive techniques (e.g., steroids), low remission rates, prolonged illnesses, and an increased frequency of surgical procedures have prompted the search for more targeted and precision therapeutic approaches. IBD is a complex disease resulting from both genetic and environmental factors, but several recent studies have highlighted the potential pivotal contribution of gut microbiota dysbiosis. Gut microbiota are known to modulate the immune status of the gut by producing metabolites that are encoded in biosynthetic gene clusters (BGCs) of the bacterial genome. Here, we show a targeted and high-throughput screening of more than 90 biosynthetic genes in 41 gut anaerobes, through downselection using available bioinformatics tools, targeted gene manipulation in these genetically intractable organisms using the Nanoligomer platform, and identification and synthesis of top microbiome targets as a Nanoligomer BGC cocktail (SB_BGC_CK1, abbreviated as CK1) as a feasible precision therapeutic approach. Further, we used a host-directed immune target screening to identify the NF-κB and NLRP3 cocktail SB_NI_112 (or NI112 for short) as a targeted inflammasome inhibitor. We used these top two microbe- and host-targeted Nanoligomer cocktails in acute and chronic dextran sulfate sodium (DSS) mouse colitis and in TNFΔARE/+ transgenic mice that develop spontaneous Crohn's like ileitis. The mouse microbiome was humanized to replicate that in human IBD through antibiotic treatment, followed by mixed fecal gavage from 10 human donors and spiked with IBD-inducing microbial species. Following colonization, colitis was induced in mice using 1 week of 3% DSS (acute) or 6 weeks of 3 rounds of 2.5% DSS induction for a week followed by 1 week of no DSS (chronic colitis model). Both Nanoligomer cocktails (CK1 and NI112) showed a strong reduction in disease severity, significant improvement in disease histopathology, and profound downregulation of disease biomarkers in colon tissue, as assessed by multiplexed ELISA. Further, we used two different formulations of intraperitoneal injections (IP) and Nanoligomer pills in the chronic DSS colitis model. Although both formulations were highly effective, the oral pill formulation demonstrated a greater reduction in biochemical markers compared to IP. A similar therapeutic effect was observed in the TNFΔARE/+ model. Overall, these results point to the potential for further development and testing of this inflammasome-targeting host-directed therapy (NI112) and more personalized microbiome cocktails (CK1) for patients with recalcitrant IBD.

Dysphagia Prevalence in Brazil, UK, China, and Indonesia and Dysphagic Patient Preferences.

Dysphagia is common, but there is limited information about its prevalence and patient preferences regarding dosage forms (oral solids, liquids, topical, etc.) in Brazil, China, the United Kingdom (UK), and Indonesia. We conducted an online survey of 1000 adults from each country, without any required disease, to estimate the prevalence of dysphagia in these four nations and the dosage form preferences among UK patients. A total of 36.9%, 40.5%, 54.9%, and 64.5% from the UK, Indonesia, Brazil, and China, respectively, had an Eating Assessment Tool (EAT-10) score of ≥3 (indicative of dysphagia). Only 2% of UK respondents and 5% of Brazilian respondents reported a formal diagnosis of dysphagia. Indonesian (74%) and Chinese respondents (77%) were more likely than Brazilian (52%) and UK respondents (45%) to report that their swallowing problems affected their ability to adhere to medication instructions. Liquids were the oral medication formulation most preferred by those who reported difficulty swallowing. To conclude, substantial populations have difficulty swallowing, which can translate into an access issue for medical treatment. The availability of people's preferred dosage forms may help alleviate the adherence issues associated with difficulty swallowing and the concomitant effects on health outcomes.

Oral food-derived whey protein isolate-Tremella fuciformis polysaccharides pickering emulsions with adhesive ability to delivery magnolol for targeted treatment of ulcerative colitis

Magnolol (Mag) is a promising natural compound with therapeutic potential for ulcerative colitis (UC). Here we designed and fabricated an oral food-grade whey protein isolate-Tremella fuciformis polysaccharides (WPI-TFPS) stabilized pickering emulsions to encapsulate Mag (Mag-WPI-TFPS) for targeted treatment of UC. With the assistance of the WPI-TFPS, pickering emulsions were well encapsulated and formed stable microparticles with a particle size of approximately 9.49 ± 0.047 μm, a 93.63 ± 0.21 % encapsulation efficiency and a loading efficiency of 21.53 ± 0.01 %. In vitro, the formulation exhibited sustained-release properties in simulated colon fluid with a cumulative release rate of 60.78 % at 48 h. In vivo, the Mag-WPI-TFPS specifically accumulated in the colon tissue for 24 h with stronger fluorescence intensity, which demonstrated that TFPS and WPI had a good adherence ability to inflamed mucosa by electrostatic attraction and ligand-receptor interactions. As expected, compared with Free-Mag, the oral administration of Mag-WPI-TFPS remarkably alleviated the symptoms of UC and protected the colon tissue in DSS-induced UC mice. More importantly, WPI-TFPS enhanced gut microbiota balance by increasing the diversity and relative abundances of Lactobacillaceae and Firmicutes. Overall, this study presents a convenient, eco-friendly, food-derived oral formulation with potential as a dietary supplement for targeted UC treatment.