Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ.

Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.

High throughput metabolomics explores the mechanism of Jigucao capsules in treating Yanghuang syndrome rats using ultra-performance liquid chromatography quadrupole time of flight coupled with mass spectrometry.

To explore the potential mechanism of the Chinese patent medicine Jigucao capsule in treating the serum metabolic profile of rats with Yanghuang syndrome, zingiber officinale Rosc. and ethanol simulates the syndrome background of traditional Chinese medicine and uses α-naphthyl isothiocyanate to induce liver damage in rats to prepare a Yanghuang syndrome model. The histopathological observation and the determination of biochemical indexes evaluate the therapeutic effect of the Jigucao capsule, and the metabolomic method analyzes the mechanism of the Jigucao capsule against Yanghuang syndrome. Jigucao capsule reduces the number of inflammatory cells, inhibits the proliferation of bile duct epithelial cells and hepatocyte necrosis. Compared with Yanghuang syndrome rats, the levels of alanine aminotransferase, alkaline phosphatase, and total bile acid were significantly reduced (P < 0.05). Furthermore, Jigucao capsule significantly reversed the abnormal levels of glucose 1-phosphate, phenylalanyl-cysteine, taurodeoxycholic acid, lysoPC (22:6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z), lysoPC (15:0), lysoPC (P-18:0), 7alpha-hydroxy-3-oxo-4-cholestenoate and 15(S)-hydroxyeicosatrieic acid and regulated part of the lipid metabolism and carbohydrate metabolism, Jigucao capsule has a therapeutic effect on Yanghuang syndrome rats. In short, this study sets for the first time elaborated on the underlying mechanism of Jigucao capsule resistance to Yanghuang syndrome rats from a metabolomics perspective, providing the basic data for the pharmacodynamic studies of the Jigucao capsule.

The efficacy and safety of different bismuth agents in Helicobacter pylori first-line eradication: A multicenter, randomized, controlled clinical trial.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of bismuth pectin capsules and bismuth pectin granules in the first-line quadruple treatment of Helicobacter pylori (H. pylori). METHODS: This study was a multicenter, randomized, open-labelled controlled clinical trial. Patients with a H. pylori infection were randomized into 4 groups (1:1:1:1) and treated with a 14-day bismuth-containing quadruple therapy. The 4 groups received either bismuth potassium citrate capsules (220 mg), colloidal bismuth pectin capsules (200 mg), bismuth pectin granules (150 mg), or bismuth pectin granules (300 mg). The primary outcome was the eradication rate of H. pylori. The secondary outcomes included symptom improvement, patient compliance, and incidence of adverse events. This study was registered at ClinicalTrials.gov (NCT04209933). RESULTS: A total of 240 patients were included in this study, and 211 patients completed the follow-up. An intention-to-treat analysis showed that the H. pylori eradication rates of the 4 groups were 73.3%, 76.7%, 75.0%, and 71.7%, respectively. The per-protocol analysis showed that the H. pylori eradication rates of the 4 groups were 86.3%, 82.1%, 83.3%, and 86.0%. There was no significant difference among the 4 groups in the H. pylori eradication rate (P > .05). There were also no significant differences in the symptom improvement rate, overall adverse reaction rate, or patient compliance among the 4 groups. CONCLUSIONS: Bismuth pectin capsules and bismuth pectin granules had similar efficacy and safety for H. pylori eradication compared to bismuth potassium citrate. These data suggest that bismuth pectin can be an alternative to bismuth potassium citrate to eradicate H. pylori when using bismuth-containing quadruple therapy.

Microencapsulated Isoniazid-Loaded Metal-Organic Frameworks for Pulmonary Administration of Antituberculosis Drugs.

Tuberculosis (TB) is an infectious disease that causes a great number of deaths in the world (1.5 million people per year). This disease is currently treated by administering high doses of various oral anti-TB drugs for prolonged periods (up to 2 years). While this regimen is normally effective when taken as prescribed, many people with TB experience difficulties in complying with their medication schedule. Furthermore, the oral administration of standard anti-TB drugs causes severe side effects and widespread resistances. Recently, we proposed an original platform for pulmonary TB treatment consisting of mannitol microspheres (Ma MS) containing iron (III) trimesate metal-organic framework (MOF) MIL-100 nanoparticles (NPs). In the present work, we loaded this system with the first-line anti-TB drug isoniazid (INH) and evaluated both the viability and safety of the drug vehicle components, as well as the cell internalization of the formulation in alveolar A549 cells. Results show that INH-loaded MOF (INH@MIL-100) NPs were efficiently microencapsulated in Ma MS, which displayed suitable aerodynamic characteristics for pulmonary administration and non-toxicity. MIL-100 and INH@MIL-100 NPs were efficiently internalized by A549 cells, mainly localized in the cytoplasm. In conclusion, the proposed micro-nanosystem is a good candidate for the pulmonary administration of anti-TB drugs.

Enteric coating of nanostructured lipid carriers (NLCs) and enteric coating of hard gelatin capsules filled with NLCs: Feasibility studies.

Nanostructured lipid carriers (NLCs) of asenapine maleate (ASPM) were enteric coated with polymethacrylate polymers (Eudragit®) for oral delivery. The present study aimed to compare the feasibility of direct enteric coating of NLCs and enteric coating of hard gelatin capsules filled with lyophilized ASPM-NLCs. Organic solution of Eudragit® was prepared using acetone containing 3% v/v water, acetone or ethanol. Aqueous dispersion of Eudragit® was obtained by neutralization with base. Capsules were enteric coated by dip-coating method with 3:2 ratio of Eudragit® L100-55:S100 (7.5-12.5% w/v). ASPM-NLCs showed particle size of 84.91±2.14nm, polydispersity index of 0.222±0.026, entrapment efficiency of 86.9±1.8% and zeta potential of -4.83±0.29 mV. TEM images showed good sphericity of the particles with the size of ≈100nm. Non-aqueous enteric coating was not successful as NLCs were precipitated in organic solvent. Aqueous enteric coated ASPM-NLCs (lipid:coat=1:2) showed an increased size (150.8±16.7nm) and zeta potential (-23.5±2.2 mV) revealing the deposition of Eudragit®. However, aqueous enteric coated ASPM-NLCs and uncoated ASPM-NLCs showed higher drug release (18.3±3.1-22.3±3.2%) in HCl solution (pH 1.2) indicating no resistance offered by direct enteric coating of NLCs; whereas enteric coated capsules showed less drug release (4.7±0.8%) in HCl solution indicating sufficient gastric protection.

Eosinophilic Esophagitis: A Review.

Importance: Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disease of the esophagus that affects an estimated 34.4/100 000 people in Europe and North America. EoE affects both children and adults, and causes dysphagia, food impaction of the esophagus, and esophageal strictures. Observations: EoE is defined by symptoms of esophageal dysfunction, such as vomiting, dysphagia, or feeding difficulties, in a patient with an esophageal biopsy demonstrating at least 15 eosinophils per high-power field in the absence of other conditions associated with esophageal eosinophilia such as gastroesophageal reflux disease or achalasia. Genetic factors and environmental factors, such as exposure to antibiotics early in life, are associated with EoE. Current therapies include proton pump inhibitors; topical steroid preparations, such as fluticasone and budesonide; dietary therapy with amino acid formula or empirical food elimination; and endoscopic dilation. In a systematic review of observational studies that included 1051 patients with EoE, proton pump inhibitor therapy was associated with a histologic response, defined as less than 15 eosinophils per high-power field on endoscopic biopsy, in 41.7% of patients, while placebo was associated with a 13.3% response rate. In a systematic review of 8 randomized trials of 437 patients with EoE, topical corticosteroid treatment was associated with histologic remission in 64.9% of patients compared with 13.3% for placebo. Patients with esophageal narrowing may require dilation. Objective assessment of therapeutic response typically requires endoscopy with biopsy. Conclusions and Relevance: EoE has a prevalence of approximately 34.4/100 000 worldwide. Treatments consist of proton pump inhibitors, topical steroids, elemental diet, and empirical food elimination, with esophageal dilation reserved for patients with symptomatic esophageal narrowing.

Chenodeoxycholic Acid Pharmacology in Biotechnology and Transplantable Pharmaceutical Applications for Tissue Delivery: An Acute Preclinical Study.

INTRODUCTION: Primary bile acids (PBAs) are produced and released into human gut as a result of cholesterol catabolism in the liver. A predominant PBA is chenodeoxycholic acid (CDCA), which in a recent study in our laboratory, showed significant excipient-stabilizing effects on microcapsules carrying insulinoma ß-cells, in vitro, resulting in improved cell functions and insulin release, in the hyperglycemic state. Hence, this study aimed to investigate the applications of CDCA in bio-encapsulation and transplantation of primary healthy viable islets, preclinically, in type 1 diabetes. METHODS: Healthy islets were harvested from balb/c mice, encapsulated in CDCA microcapsules, and transplanted into the epididymal tissues of 6 syngeneic diabetic mice, post diabetes confirmation. Pre-transplantation, the microcapsules' morphology, size, CDCA-deep layer distribution, and physical features such as swelling ratio and mechanical strength were analyzed. Post-transplantation, animals' weight, bile acids', and proinflammatory biomarkers' concentrations were analyzed. The control group was diabetic mice that were transplanted encapsulated islets (without PBA). RESULTS AND CONCLUSION: Islet encapsulation by PBA microcapsules did not compromise the microcapsules' morphology or features. Furthermore, the PBA-graft performed better in terms of glycemic control and resulted in modulation of the bile acid profile in the brain. This is suggestive that the improved glycemic control was mediated via brain-related effects. However, the improvement in graft insulin delivery and glycemic control was short-term.

Matrix Effects on the Delivery Efficacy of Bifidobacterium animalis subsp. lactis BB-12 on Fecal Microbiota, Gut Transit Time, and Short-Chain Fatty Acids in Healthy Young Adults.

Probiotics are consumed in fermented dairy products or as capsules for their putative health benefits. However, little research has been done to evaluate the effects of the delivery matrix on the health benefits of probiotics in humans. To examine the effects of delivering Bifidobacterium animalis subsp. lactis BB-12 (BB-12) (log10 10 ± 0.5 CFU/day) via a yogurt smoothie versus a capsule, we monitored the fecal microbiota, gut transit times (GTTs), and fecal excretion of short-chain fatty acids (SCFAs) in healthy adults. In a randomized, four-period, crossover study performed in a partially blind manner, 36 adults were recruited and randomly assigned to four treatments: control yogurt smoothie (YS), yogurt smoothie with BB-12 added prefermentation (PRE), yogurt smoothie with BB-12 added postfermentation (POST), and capsule containing BB-12 (CAP). Participants' fecal microbiota was assessed using 16S rRNA sequencing, GTTs via SmartPill, and fecal SCFAs by gas chromatography (GC) before (baseline) and after each intervention. Participants had significantly higher percentage of Streptococcus after consuming YS versus CAP (P = 0.01). Bifidobacterium-specific terminal restriction fragment length polymorphism analysis revealed a significantly higher percentage of B. animalis after consuming PRE and POST compared to baseline, YS, CAP, and final washout (P < 0.0001). The predominant SCFAs were negatively correlated with GTTs. Consumption of BB-12 delivered in a yogurt smoothie or capsule did not significantly alter the composition of the gut microbiota, GTTs, or fecal SCFA concentration of the study cohort. However, daily consumption of BB-12 in yogurt smoothie may result in higher relative abundance of B. animalis in healthy adults. (This trial has been registered at ClinicalTrials.gov under identifier NCT01399996.) IMPORTANCE Bifidobacterium animalis subsp. lactis BB-12 is a probiotic strain that has been used worldwide since 1985. It has commonly been delivered in fermented dairy products for perceived benefits associated with gut health and enhanced immune function. In addition to fermented dairy products, many new probiotic-containing alternatives such as probiotic-containing juice, probiotic-containing chocolate, and capsules have been developed. While these products provide more options for people to access probiotics, little research has been done on the effect of delivery matrix (dairy versus nondairy) on their efficacy in humans. In addition, it was unclear how yogurt fermentation may influence the survival of BB-12 in the product or on its performance in vivo. The significance of our study is in simultaneously assessing the effect of BB-12, alone and in different delivery vehicles, on the gut transit time, fecal short-chain fatty acids, and the composition of the gut microbiota of the study cohort.

Insight into the structural, chemical and surface properties of proteins for the efficient ultrasound assisted co-encapsulation and delivery of micronutrients.

Three different proteinaceous biopolymers, namely, egg white protein (EWP), soy protein isolate (SPI) and corn protein isolate (CPI) were used as protective shell materials to encapsulate micronutrients via an ultrasonic encapsulation technique. It was found that the physicochemical properties of the three protein-based matrices, including surface/total thiol (-SH) content, surface activity and denaturation temperature were the key factors that influenced the shell formation and stability. The EWP and CPI-shelled microcapsules reduced the degradation of the encapsulated vitamins by 20% and 40% after exposure to heating and UV-light irradiation. A double emulsion technique was further developed to co-encapsulate both oil- (vitamin A and D) and water-soluble (vitamin B, C and minerals) micronutrients. In-vitro digestion study showed that the proteinaceous microcapsules enable a sustained release of micronutrients, demonstrating their potential for food fortification applications.

Formulation and Characterization of Microcapsules Encapsulating PC12 Cells as a Prospective Treatment Approach for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurological disorder, associated with decreased dopamine levels in the brain. The goal of this study was to assess the potential of a regenerative medicine-based cell therapy approach to increase dopamine levels. In this study, we used rat adrenal pheochromocytoma (PC12) cells that can produce, store, and secrete dopamine. These cells were microencapsulated in the selectively permeable polymer membrane to protect them from immune responses. For fabrication of the microcapsules, we used a modified Buchi spray dryer B-190 that allows for fast manufacturing of microcapsules and is industrially scalable. Size optimization of the microcapsules was performed by systematically varying key parameters of the spraying device. The short- and long-term stabilities of the microcapsules were assessed. In the in vitro study, the cells were found viable for a period of 30 days. Selective permeability of the microcapsules was confirmed via dopamine release assay and micro BCA protein assay. We found that the microcapsules were permeable to the small molecules including dopamine and were impermeable to the large molecules like BSA. Thus, they can provide the protection to the encapsulated cells from the immune cells. Griess's assay confirmed the non-immunogenicity of the microcapsules. These results demonstrate the effective fabrication of microcapsules encapsulating cells using an industrially scalable device. The microcapsules were stable, and the cells were viable inside the microcapsules and were found to release dopamine. Thus, these microcapsules have the potential to serve as the alternative or complementary treatment approach for PD.

Qianliexin capsule exerts anti-inflammatory activity in chronic non-bacterial prostatitis and benign prostatic hyperplasia via NF-κB and inflammasome.

Qianliexin capsule (QLX) is a standardized traditional Chinese herbal preparation that has long been used to treat chronic non-bacterial prostatitis (CNP) and benign prostatic hyperplasia (BPH). This study investigated the anti-inflammatory activity of QLX in improving lower urinary tract symptoms (LUTS) associated with CNP and BPH. Rat models of CNP and BPH were induced by oestradiol or testosterone (hormonal imbalance) or chemical inflammation (carrageenan). QLX significantly relieved LUTS in CNP and BPH rat model by reducing prostate enlargement, epithelial thickness, pain response time, urine volume and bleeding time, and by improving prostatic blood flow. The expression of the pro-inflammatory cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α, the pro-inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and inflammasome components (NLRP3, caspase-1 and ASC) in CNP and BPH tissues was reduced by QLX addition. QLX treatment was followed by reduced cellular malondialdehyde and increased superoxide dismutase, catalase and glutathione peroxidase activity, consistent with antioxidant activity. Increases in Beclin-1 expression and the LC3II/I ratio following QLX treatment indicated that autophagy had been induced. QLX relieved LUTS in CNP and BPH rat models by inhibiting inflammation. The underlying mechanisms included inhibition of inflammasome activation, NF-κB activation, oxidant stress and autophagy.

In Vitro Cytotoxic Protective Effect of Alginate-Encapsulated Capsaicin Might Improve Skin Side Effects Associated with the Topical Application of Capsaicin.

Chronic neuropathic pain, particularly peripheral pain, is a cause of great concern for diabetic patients. Current treatments include numerous agents such as capsaicinoids, a known deterrent of neuropathic pain despite the inconvenience associated with local side effects. In this context, the current work aims to elucidate the potential mechanisms involved in cytotoxicity by capsaicin and proposes an efficient formulation of capsaicin in alginate microcapsules, which significantly reduces side effects from capsaicin topical administration. For this, human dermal fibroblast cells were treated with alginate-microencapsulated capsaicin extracts and screened for potential cytotoxic effects produced by the treatment. Cell viability and morphology were examined, as well as oxidative stress status and anti-inflammatory potential. Our results show that the alginate encapsulated formulation of capsaicin exerted lower cytotoxic effects on human dermal fibroblasts as measured by cell viability and reactive oxygen species (ROS) production. Furthermore, the expression profiles of inflammatory cytokines were significantly altered by the treatment as compared with the control culture.

Effectiveness of fecal microbiota transplant for the treatment of Clostridioides difficile diarrhea: a systematic review and meta-analysis.

Clostridioides difficile is a major cause of health-care related infections and antibiotic-associated diarrhea. High recurrence rates following antibiotic treatment, along with the emergence of hypervirulent and multidrug resistant ribotypes makes essential the development of safe, effective, novel therapies for the treatment of C. difficile infections. The primary outcome evaluated in this meta-analysis was the effectiveness of fecal microbiota transplantation (FMT). Secondary outcomes were the proportion of patients suffering adverse effects along with the most effective administration route. The mean treatment effectiveness was 82% (95% CI: 75-89). Overall, patients receiving FMT via colonoscopy experienced more adverse effects than patients whom received enema, or oral capsules (71·6% vs 40·2%, and 35·3% respectively). Comparing administration of FMT by colonoscopy versus enema resulted in a Hedges' g of -0·74 (95% CI of -0·9 to -0·58), indicating a slight advantage in favor of colonoscopy. The comparison between colonoscopy and capsule returned a Hedges' g of 0·44 (95% CI of 0·20-0·69), indicating that delivery of the FMT by capsule was statistically significantly more effective. FMT provides an effective and safe treatment for C. difficile diarrhea. Further research into the efficacy of different preparation protocols is needed.

Effect of silibinin capsules combined with lifestyle modification on hepatic steatosis in patients with chronic hepatitis B.

The coexistence of HBV infection and hepatic steatosis is a novel characteristic of liver disease. Silibinin capsules (SC) is a silybin-phospholipid complex containing silybin as the bioactive component, which exerts a remarkable biological effect on various liver diseases, including nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to investigate (1) the prevalence of hepatic steatosis in the general population and patients with chronic hepatitis B (CHB) and (2) to evaluate the effect of SC combined with therapeutic lifestyle changes (TLC) compared with TLC alone on hepatic steatosis in patients with CHB. A total of 16,451 individuals underwent transient elastography (TE) with the control attenuation parameter (CAP) measurement, among which the prevalence of hepatic steatosis was 31.1% in patients with CHB and 42.2% in the general population. The prevalence of hepatic steatosis differed between patients with CHB and the general population at an age of 40 years or older but was similar in individuals aged 39 years or younger (p < 0.05). Furthermore, in patients with CHB presenting hepatic steatosis, the post-6-month relative reduction in CAP in the SC combined with TLC group (p = 0.001) was significantly greater than in the TLC alone group (p = 0.183). The CAP distribution of different steatosis grades (S1, S2, and S3) in the SC combined with TLC group was decreased and S0 (CAP < 248 dB/m) increased significantly, but not significant in the TLC group. Thus, SC combined with TLC may effectively improve hepatic steatosis in patients with CHB.

EndoPil: A Magnetically Actuated Swallowable Capsule for Weight Management: Development and Trials.

Intragastric balloons (IGBs), by occupying the stomach space and prolonging satiety, is a promising method to treat obesity and consequently improves its associated comorbidities, e.g. coronary heart disease, diabetes, and cancer. However, existing IGBs are often tethered with tubes for gas or liquid delivery or require endoscopic assistance for device delivery or removal, which are usually uncomfortable, costly, and may cause complications. This paper presents a novel tetherless, magnetically actuated capsule (EndoPil) which can deploy an IGB inside the stomach after being swallowed and being activated by an external magnet. The external magnet attracts a small magnet inside the EndoPil to open a valve, triggering the chemical reaction of citric acid and potassium bicarbonate to produce carbon dioxide gas, which inflates a biocompatible balloon (around 120 mL). A prototype, 13 mm in diameter and 35 mm in length, was developed. Simulations and bench-top tests were conducted to test the force capability of the magnetic actuation mechanism, the required force to activate the valve, and the repeatability of balloon inflation. Experiments on animal and human were successfully conducted to demonstrate the safety and feasibility of inflating a balloon inside the stomach by an external magnet.

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

BACKGROUND: Most people with cystic fibrosis (CF) (80% to 90%) need pancreatic enzyme replacement therapy (PERT) to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of PERT is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. OBJECTIVES: To evaluate the efficacy and safety of PERT in children and adults with CF and to compare the efficacy and safety of different formulations of PERT and their appropriateness in different age groups. Also, to compare the effects of PERT in CF according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 07 November 2019. We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 26 December 2019. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials in people of any age, with CF and receiving PERT, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other PERT preparations. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias and quality of the evidence (GRADE) of the trials included in the review. MAIN RESULTS: 14 trials were included in the review (641 children and adults with CF), two of these were parallel trials and 12 were cross-over trials. Interventions included different enteric and non-enteric-coated preparations of varying formulations in comparison to each other. The number of participants in each trial varied between 14 and 129. 13 trials were for a duration of four weeks and one trial lasted seven weeks. The majority of the trials had an unclear risk of bias from the randomisation process as the details of this were not given; they also had a high risk of attrition bias and reporting bias. The quality of the evidence ranged from moderate to very low. We mostly could not combine data from the trials as they compared different formulations and the findings from individual trials provided insufficient evidence to determine the size and precision of the effects of different formulations. AUTHORS' CONCLUSIONS: There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over trials is likely to underestimate the level of inconsistency between the results of the trials due to over-inflation of CIs from the individual trials.There is no evidence on the long-term effectiveness and risks associated with PERT. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed trial that can answer these questions.

Encapsulation of Lactobacillus rhamnosus in Hyaluronic Acid-Based Hydrogel for Pathogen-Targeted Delivery to Ameliorate Enteritis.

Probiotics were found to be effective in ameliorating the microbial dysbiosis and inflammation caused by intestinal pathogens. However, biological challenges encountered during oral delivery have greatly limited their potential health benefits. Here, a model probiotic (Lactobacillus rhamnosus) was encapsulated in an intestinal-targeted hydrogel to alleviate bacterial enteritis in a novel mode. The hydrogel was prepared simply by the self-cross-linking of thiolated hyaluronic acid. Upon exposure to H2S which were excreted by surrounding intestinal pathogens, the hydrogel can locally degrade and rapidly release cargos to compete with source pathogens in turn for binding to the host. The mechanical properties of hydrogel were studied by rheological analysis, and the ideal stability was achieved at a polymer concentration of 4% (w/v). The morphology of the optimal encapsulation system was further measured by a scanning electron microscope, exhibiting uniform payload of probiotics. Endurance experiments indicated that the encapsulation of L. rhamnosus significantly enhanced their viability under gastrointestinal tract insults. Compared with free cells, encapsulated L. rhamnosus exerted better therapeutic effect against Salmonella-induced enteritis with negligible toxicity in vivo. These results demonstrate that this redox-responsive hydrogel may be a promising encapsulation and delivery system for improving the efficacy of orally administered probiotics.

An orally delivered microbial cocktail for the removal of nitrogenous metabolic waste in animal models of kidney failure.

Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects.

Nanoencapsulation approaches for oral delivery of vitamin A.

Vitamin A is essential to human health. Encapsulation in lipid nanoparticles was used to overcome vitamin A poor water solubility in beverages. This work aimed to develop and characterize lipid nanoparticles, containing vitamin A, for food fortification, assuring its stability and oral bioaccessibility. Lipid nanoparticles optimized for the oral administration of vitamin A using the hot homogenization method. The nanoparticles subjected to conditions used in food processing suffered no changes in their size or vitamin content. In vitro assays simulating gastrointestinal digestion suggested that the nanoparticles are not altered in the stomach, and the biocompatibility of the formulations showed no toxicity in fibroblasts. With the developed nanoparticles 80% of the added vitamin reached the intestine in the digestibility assay, demonstrating suitability as a nanotechnology application in the food research for the food industry.

Appropriateness of oral dosage form modification for aged care residents: a video-recorded observational study.

Background Dosage forms of oral medications are frequently modified in aged care facilities by crushing/splitting tablets or opening capsules to facilitate medication administration for residents with swallowing difficulties. These practices pose safety concerns including the risk of adverse events resulting from loss of dose during transfer and alteration in the rate of absorption. Objective To identify the incidence, methods, and appropriateness of oral dosage form modification practices in aged care facilities. Setting A purposive sample of four urban and regional aged care facilities in Queensland, Australia. Method The processes of modification of oral dosage forms were observed and video-recorded using an action camera placed on medication trolleys. Each video was then reviewed and the details of the medication modification processes were recorded in a data collection form. The appropriateness of the practices of dosage form modification was evaluated against existing national guideline (Australian Don't Rush to Crush Handbook). Deviations from the instructions in the guideline were considered as inappropriate practice. Main outcome measure Incidence and characteristics of inappropriate modification of oral dosage forms. Results Oral dosage forms were modified in 25.7% of 810 observed medications. The most common methods of dosage form modification included crushing tablets with a manual crushing device (71.6%), cutting/splitting tablets (20.2%), and opening capsules (4.3%). According to the national guideline, 12.5% of the modification instances were inappropriate. Inappropriate practices were commonly associated with the suboptimal methods of medication preparation where medications were unsuitably modified, mixed, spilled, or incompletely dosed. Conclusion The modification of oral dosage forms seems a common practice in aged care facilities in Queensland. However, some of these modifications do not comply with the requirements of good practice according to existing guidelines. Healthcare workers in aged care facilities need to be supported and upskilled with effective training to promote the best and safest practices of ODF modification.