Assessing adherence to infusion-based biologic therapies in patients with inflammatory bowel disease

BackgroundThe intravenous biologics infliximab and vedolizumab are effective long-term therapies for inflammatory bowel disease (IBD). Though highly effective, suboptimal adherence may result in loss of response and adverse sequelae. The extent and outcomes of suboptimal adherence with intravenous biologics, including in IBD, requires further evaluation.ObjectivesTo ascertain adherence to infliximab and vedolizumab infusions, and determine factors associated with poorer adherence within an IBD cohort.MethodsA retrospective single-centre cohort study of IBD patients, assessing adherence to infliximab and vedolizumab over 2 years (July 1, 2017 to June 30, 2019) was conducted. Medical and pharmacy dispensing records were used to determine date of infusion. Adherence was assessed using the continuous, multiple interval measure of medication gaps (CMG). Objectively measured disease remission was achieved if one or more of endoscopic remission, faecal calprotectin <100 μg/mL and/or CRP <5 mg/mL occurred within 3 months of end of follow-up. Bivariate analysis and multiple linear regression elucidated factors associated with poorer adherence.ResultsOf 193 IBD patients, 132 (68.4%) had Crohn's disease. One hundred and thirty six (70.5%) patients received infliximab and 57 (29.5%) received vedolizumab with a median 13 [IQR 11–14] doses administered per patient over 2 years. Adherence according to CMG was similar between infliximab and vedolizumab groups (median 1.5% vs 1.2%, p = 0.31). In multiple linear regression analysis male sex, shorter IBD duration and clinic non-attendances were each associated with poorer adherence (Beta 4.69, 3.90, 3.56 respectively, p < 0.05) and objective disease remission was inversely associated with poorer adherence (Beta ?3.27, p < 0.05).ConclusionThere was a wide range of adherence to biologic infusions in this IBD cohort with poorer adherence associated with patient related factors. Conversely, objectively measured remission was strongly associated with adherence. This emphasises the need for targeted interventions to improve adherence and monitoring, and mitigate treatment delays.     

Safety and tolerability of Empagliflozin use during the holy month of Ramadan by fasting patients with type 2 diabetes: A prospective cohort study

BackgroundType 2 Diabetes Mellitus (T2DM) patients are exposed to a 7.5 times higher risk of hypoglycemia while fasting during Ramadan. Relevant diabetes guidelines prioritize the use of SGLT2 inhibitors over other classes. There is a great need to enrich data on their safe and effective use by fasting patients at greater risk of hypoglycemia. Therefore, this study aims to assess the safety and tolerability of Empagliflozin in T2DM Muslim patients during Ramadan.MethodologyA prospective cohort study was conducted for adult Muslim T2DM patients. Patients who met the inclusion criteria were categorized into two sub-cohorts based on Empagliflozin use during Ramadan (Control versus Empagliflozin). The primary outcomes were the incidence of hypoglycemia symptoms and confirmed hypoglycemia. Other outcomes were secondary. All patients were followed up to eight weeks post-Ramadan. A propensity score (PS) matching and Risk Ratio (RR) were used to report the outcomes.ResultsAmong 1104 patients with T2DM who were screened, 220 patients were included, and Empagliflozin was given to 89 patients as an add-on to OHDs. After matching with PS (1:1 ratio), the two groups were comparable. The use of other OHDs, such as sulfonylurea, DPP4 inhibitors, and Biguanides, was not statistically different between the two groups. The risk of hypoglycemia symptoms during Ramadan was lower in patients who received Empagliflozin than in the control group (RR 0.48 CI 0.26, 0.89; p-value = 0.02). Additionally, the risk of confirmed hypoglycemia was not statistically significant between the two groups (RR 1.09 CI 0.37, 3.22; p-value = 0.89).ConclusionEmpagliflozin use during Ramadan fasting was associated with a lower risk of hypoglycemia symptoms and higher tolerability. Further randomized control trials are required to confirm these findings.     

Microneedle-based devices for point-of-care infectious disease diagnostics

Recent infectious disease outbreaks, such as COVID-19 and Ebola, have highlighted the need for rapid and accurate diagnosis to initiate treatment and curb transmission. Successful diagnostic strategies critically depend on the efficiency of biological sampling and timely analysis. However, current diagnostic techniques are invasive/intrusive and present a severe bottleneck by requiring specialist equipment and trained personnel. Moreover, centralised test facilities are poorly accessible and the requirement to travel may increase disease transmission. Self-administrable, point-of-care (PoC) microneedle diagnostic devices could provide a viable solution to these problems. These miniature needle arrays can detect biomarkers in/from the skin in a minimally invasive manner to provide (near-) real-time diagnosis. Few microneedle devices have been developed specifically for infectious disease diagnosis, though similar technologies are well established in other fields and generally adaptable for infectious disease diagnosis. These include microneedles for biofluid extraction, microneedle sensors and analyte-capturing microneedles, or combinations thereof. Analyte sampling/detection from both blood and dermal interstitial fluid is possible. These technologies are in their early stages of development for infectious disease diagnostics, and there is a vast scope for further development. In this review, we discuss the utility and future outlook of these microneedle technologies in infectious disease diagnosis.     

Association between non-pharmacological therapy and healthcare use and expenditure of patients with diabetes mellitus

This study explored the sociodemographic and clinical characteristics of patients with diabetes who incorporated two non-pharmacological therapies into their lifestyle and the association between non-pharmacological therapy and healthcare utilization and expenditure. In the USA, 26.4 million people were reportedly diagnosed with diabetes and treated with diet modification or physical activity in the 2019 Medical Expenditure Panel Survey. Physical activity was defined as moderate-to-vigorous physical exercise five times per week, whereas dietary modification involved healthy eating that reduced glucose levels. Only 4.8 million patients with diabetes did not integrate any non-pharmacological intervention into their therapy regimen. Those who did not include non-pharmacological interventions had higher annual total healthcare expenditures (M = $18,428) than those who incorporated either single (M = $17,058) or dual intervention (M = $15,134). A significant difference was observed in prescribed medicine utilization per year for those who did not include lifestyle modifications or non-pharmacological interventions. Propensity score-matched participants revealed significant differences in hospital stays, outpatient visits, and emergency department expenditures. Patients with diabetes who adhered to two non-pharmacological interventions showed significantly lower healthcare utilization. Being active and following a healthy diet can help prevent the progression of diabetes mellitus complications and reduce the cost associated with diabetes.     

Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)–DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI–DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA–DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.     

Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication

Nowadays, nanotechnology is revolutionizing the approaches to different fields from manufacture to health. Carbon nanotubes (CNTs) as promising candidates in nanomedicine have great potentials in developing novel entities for central nervous system pathologies, due to their excellent physicochemical properties and ability to interface with neurons and neuronal circuits. However, most of the studies mainly focused on the drug delivery and bioimaging applications of CNTs, while neglect their application prospects as therapeutic drugs themselves. At present, the relevant reviews are not available yet. Herein we summarized the latest advances on the biomedical and therapeutic applications of CNTs in vitro and in vivo for neurological diseases treatments as inherent therapeutic drugs. The biological mechanisms of CNTs-mediated bio-medical effects and potential toxicity of CNTs were also intensely discussed. It is expected that CNTs will exploit further neurological applications on disease therapy in the near future.     

Accelerated liver recovery after acute CCl4 poisoning in rats treated with sodium phthalhydrazide

Pharmacotherapy of hepatobiliary disorders is an important issue due to the high prevalence of liver failure, toxic and viral hepatitis and cirrhosis. The number of stimuli that can potentially induce or accelerate liver recovery is limited; in our study we selected sodium phthalhydrazide, which has been found to promote liver regeneration after partial hepatectomy. We examined the effects of phthalhydrazide on liver morphometric, histological and biochemical parameters in rats intoxicated with CCl₄. Accelerated liver recovery after CCl₄ intoxication in phthalhydrazide-treated animals was evidenced by increased number of liver sinusoidal cells, reduced focal necrosis of hepatocytes and reduced perifocal leukocyte infiltration. Decreased plasma levels of pro-inflammatory cytokines TNF-α and IL-18 and decreased concentrations of IL-6 and IFN-γ in liver homogenates were associated with reduced severity of cholestasis and normalized hepatic protein synthesis in CCl₄-intoxicated rats exposed to phthalhydrazide. Anti-inflammatory and immunomodulating properties of phthahlhydrazide can be an important factor contributing to accelerated liver recovery at early stages of acute CCl₄-toxic liver impairment.     

Nutraceuticals use and type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a complicated metabolic disease and has become one of the significant medical problems worldwide. Researchers aim to provide fine-tuned treatment for T2DM with minimal exposed side effects. Nutraceuticals are compounds or materials and emerging evidence suggests that the use of nutraceuticals has recently been recognized as a promising option for the prevention and management of T2DM, such as probiotics and prebiotics, Vitamin D, n-3 long-chain polyunsaturated fatty acids, and Plant-derived nutraceuticals. This review attempts to show the most popular nutraceuticals and review their effects and possible mechanisms in the prevention or glycemic control of T2DM.     

Clinical factors associated with increased length of stay and readmission in patients with medication-related hospital admissions: a retrospective study

BackgroundAdverse drug events (ADEs) remain a key contributor to hospitalisations, resulting in long hospital stays and readmissions. Information pertaining to the specific medications and clinical factors associated with these outcomes is limited. Hence, a better understanding of these factors and their relationship to ADEs is required.ObjectivesTo investigate medications involved, clinical manifestations of ADE-related hospitalisations, and their association with length of stay and readmission.MethodsA retrospective medical record review of patients admitted to a major, tertiary referral hospital in NSW, Australia, from January 2019 to August 2020 was conducted. ADEs were identified using Australian Refined Diagnosis Related Group (AR-DRG) codes: X40, X61, X62 and X64. Medications were classified per the Anatomical Therapeutic Chemical (ATC) classification system and clinical symptoms were classified per the International Classification of Disease (ICD) 9-CM. Logistic regression was performed to assess the relationship between medication and presentation classes with length of stay (≥2 days vs <2 days) and readmission.ResultsThere were 125 patients who met inclusion criteria (median age = 64 [interquartile range, 45–75] years; 53.6% male). Anti-thrombotic agents, opioids, antidepressants, antipsychotics, insulins and NSAIDs were the most implicated pharmacological classes. Neurological medications and falls were associated with a length of stay ≥2 days (adjusted odds ratio [aOR] 3.92, 95% confidence interval [CI] 1.48–10.33 and aOR 3.24, 95% CI 1.05–10.06, respectively). Neurological medications and neurological and cognitive disorders were associated with an increased likelihood of 90-day readmission (aOR 2.63, 95% CI 1.05–6.57 and aOR 3.20, 95% CI 1.17–8.75, respectively).ConclusionThis study identified neurological medications as high-risk for increased length of stay and readmission in those hospitalised due to ADEs. This highlights the need for judicious prescribing and monitoring of these medications.     

Voriconazole Ternary Micellar Systems for the Treatment of Ocular Mycosis: Statistical Optimization and In Vivo Evaluation

Voriconazole (VRC) is a broad spectrum, second generation triazole antifungal. The main use of VRC is via the oral and intravenous route. The study aimed to formulate VRC into ternary micellar systems (TMSs) for the topical treatment of ocular mycosis. TMSs were successfully prepared by water addition/solvent evaporation method, applying a 3-factor D-optimal design. The numerical optimization process suggested an optimal formula (OTMS) composed of total Pluronics to drug weight ratio of 22.89: 1, 1:1 weight ratio of Pluronic® P123 and F68, and 2% w/v of Labrasol. OTMS had high solubilization efficiency of 98.0%, small micellar size of 21.8 nm and suitable zeta potential and polydispersity index values of -9.0 mV and 0.261, respectively. OTMS exhibited acceptable stability for 3 months. Transmission electron microscopy demonstrated the spherical morphology of micelles. OTMS was expected to cause no ocular irritation or blurring in vision as reflected by pH and refractive index measurements. The histopathological study revealed the safety of OTMS for ocular use. The fungal susceptibility testing using Candida albicans demonstrated the superiority of OTMS to VRC suspension, with greater and more durable growth inhibition. Therefore, ocular application of optimized VRC-loaded TMSs can be a promising treatment for ocular mycosis.     

Precise delivery of obeticholic acid via nanoapproach for triggering natural killer T cell-mediated liver cancer immunotherapy

Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared via ultrasonic emulsification method, with a diameter of 184 nm and good stability. In vivo biodistribution studies confirmed that the injected OCA-NE mainly accumulated in the liver and especially in LSECs and Kupffer cells. As a result, OCA-NE treatment significantly suppressed hepatic tumor growth in a murine orthotopic H22 tumor model, which performed much better than oral medication of free OCA. Immunologic analysis revealed that the OCA-NE resulted in augmented secretion of CXCL16 and IFN-γ, as well as increased NKT cell populations inside the tumor. Overall, our research provides a new evidence for the antitumor effect of receptors for primary bile acids, and should inspire using nanotechnology for precisely manipulating LSECs for liver cancer therapy     

Prevalence of complementary and alternative medicine use among rheumatoid arthritis patients in Saudi Arabia

Background and aimThe use of complementary and alternative medicine (CAM) is unexplored among Saudi rheumatoid arthritis (RA) patients. The aim of this study was to estimate the prevalence and types of CAM used among patients with RA and factors associated with their use.Experimental procedureA cross-sectional study was conducted at rheumatology clinics in two tertiary hospitals located in Riyadh, Saudi Arabia. The data was collected between May 2017 and February 2018. Unpaired Student's t-tests, Chi-square tests, and Pearson correlation tests were used to compare users vs nonusers.ResultsA total of 438 patients (mean age = 49, SD ± 15 years; 89.7% females) were included in this study. Sixty seven percent of included patients had used CAM for their RA. The majority of CAM users were female (92.1%). The most frequently used CAM products were vitamin D (47%), calcium (37%), honey (15%), ginger (13%), turmeric (11%), black seeds (8%), and fenugreek (8%). One hundred ninety-six (45%) patients believe that CAM is safe, and 287 (96%) patients took it because they believed that CAM had “added benefits”. Statistically significant differences were found for gender, RA duration, erythrocyte sedimentation rate (ESR) level, and seropositivity between CAM users and nonusers (P = 0.019, P = 0.011, P = 0.022, and P < 0.0001, respectively). A significant correlation was found between the Erythrocyte Sedimentation Rate (ESR) level, RA duration and CAM use (r = 0.110, P = 0.022 and r = 0.121, P = 0.012, respectively). These data indicated that patients who used CAM had higher ESR level and longer disease duration than patients didn’t use CAM.ConclusionThere is a high prevalence of CAM use among RA patients. CAM use was perceived to add benefit and patients using it had higher ESR. Larger studies are needed to assess the use of CAM and its impact on RA and its management.     

Predicting the Molecular Mechanism of EGFR Domain II Dimer Binding Interface by Machine Learning to Identify Potent Small Molecule Inhibitor for Treatment of Cancer

Epidermal growth factor receptor (EGFR) is a transmembrane druggable target controlling cellular differentiation, proliferation, migration, survival and invasion. EGFR activation mainly occurs by its homo/hetro dimerization molecular phenomenon leading to tumor development and invasion. Several tyrosine kinase based inhibitors were discovered as potent anti-cancer drugs. However, mutations in its kinase domain confer resistance to most of these drugs. To overcome this drug resistance, development of small molecule inhibitors disrupting the EGFR Domain II dimer binding by machine learning methods are promising. Based on this insight, a structure-based drug repurposing strategy was adopted to repurpose the existing FDA approved drugs in blocking the EGFR Domain II mediated dimerization. We identified five best repurposed drug molecules showing good binding affinity at its key arm-cavity dimer interface residues by different machine learning methods. The molecular mechanisms of action of these repurposed drugs were computationally validated by molecular electrostatics potential mapping, point mutations at the dimer arm-cavity binding interface, molecular docking and receptor interaction studies. The present machine learning strategy thus forms the basis of identifying potent and putative small molecule drugs for the treatment of different types of cancer.     

IFN regulatory Factor-1 induced macrophage pyroptosis by modulating m6A modification of circ_0029589 in patients with acute coronary syndrome

BackgroundPyroptosis is identified as a novel form of inflammatory programmed cell death and has been recently found to be closely related to atherosclerosis (AS). We found that IFN regulatory factor-1(IRF-1) effectively promotes macrophage pyroptosis in patients with acute coronary syndrome (ACS). Subsequent studies have demonstrated that circRNAs are implicated in AS. However, the underlying mechanisms of circRNAs in macrophage pyroptosis remain elusive.MethodsWe detected the RNA expression of hsa_circ_0002984, hsa_circ_0010283 and hsa_circ_0029589 in human PBMC-derived macrophages from patients with coronary artery disease (CAD). The lentiviral recombinant vector for hsa_circ_0029589 overexpression (pLC5-GFP-circ_0029589) and small interference RNAs targeting hsa_circ_0029589 and METTL3 were constructed. Then, macrophages were transfected with pLC5-GFP-circ_0029589, si-circ_0029589 or si-METTL3 after IRF-1 was overexpressed and to explore the potential mechanism of hsa_circ_0029589 involved in IRF-1 induced macrophage pyroptosis.ResultsThe relative RNA expression level of hsa_circ_0029589 in macrophages was decreased, whereas the N6-methyladenosine (m6A) level of hsa_circ_0029589 and the expression of m6A methyltransferase METTL3 were validated to be significantly elevated in macrophages in patients with ACS. Furthermore, overexpression of IRF-1 suppressed the expression of hsa_circ_0029589, but induced its m6A level along with the expression of METTL3 in macrophages. Additionally, either overexpression of hsa_circ_0029589 or inhibition of METTL3 significantly increased the expression of hsa_circ_0029589 and attenuated macrophage pyroptosis.ConclusionOur observations suggest a novel mechanism by which IRF-1 facilitates macrophage pyroptosis and inflammation in ACS and AS by inhibiting circ_0029589 through promoting its m6A modification.     

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.     

Recent insights of the role and signalling pathways of interleukin-34 in liver diseases

Liver disease is a global health problem and is a primary cause of mortality and morbidity worldwide. Specifically, it accounts for approximately two million deaths per year worldwide. The common causes of mortality are the complications of liver cirrhosis, viral hepatitis and hepatocellular carcinoma (HCC). The mechanism of immune response and infiltration of cellular immunity is essential for promoting hepatic inflammatory, especially when the liver is abundant with lymphocytes and phagocytic cells. The injured and immunity cells secret different types of interleukins (cytokines), which can directly or indirectly amplify or inhibit liver inflammation. Many types of cells can produce interleukin-34 (IL-34) that induces the release of multiple inflammatory factors in patients via interaction with various cytokines. This phenomenon leads to the enlargement of the inflammatory response to liver diseases and induces liver fibrosis. This review highlights the proposed roles of IL-34 in liver diseases and discusses the recent findings of IL-34 that support its emerging role in HCC. Specifically, the facilitating effects of these new insights on the rational development of IL-34 for targeted therapies in the future are explored.     

Characterization of organic anion transporting polypeptide 1b2 knockout rats generated by CRISPR/Cas9: a novel model for drug transport and hyperbilirubinemia disease

Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/3) as important uptake transporters play a fundamental role in the transportation of exogenous drugs and endogenous substances into cells. Rat OATP1B2, encoded by the Slco1b2 gene, is homologous to human OATP1B1/3. Although OATP1B1/3 is very important, few animal models can be used to study its properties. In this report, we successfully constructed the Slco1b2 knockout (KO) rat model via using the CRISPR/Cas9 technology for the first time. The novel rat model showed the absence of OATP1B2 protein expression, with no off-target effects as well as compensatory regulation of other transporters. Further pharmacokinetic study of pitavastatin, a typical substrate of OATP1B2, confirmed the OATP1B2 function was absent. Since bilirubin and bile acids are the substrates of OATP1B2, the contents of total bilirubin, direct bilirubin, indirect bilirubin, and total bile acids in serum are significantly higher in Slco1b2 KO rats than the data of wild-type rats. These results are consistent with the symptoms caused by the absence of OATP1B1/3 in Rotor syndrome. Therefore, this rat model is not only a powerful tool for the study of OATP1B2-mediated drug transportation, but also a good disease model to study hyperbilirubinemia-related diseases.     

Discovery of the anti-angiogenesis effect of eltrombopag in breast cancer through targeting of HuR protein

HuR (human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization (FP) based high-throughput screening (HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay (EMSA), simulation docking and surface plasmon resonance (SPR). Further, we showed that eltrombopag inhibited in vitro cell proliferation of multiple cancer cell lines and macrophages, and the in vivo anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The in vivo data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the in vitro anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells (HUVECs) mediated by macrophages with cell scratch assay and in vitro Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.     

Design and Optimization of a Novel Strategy for the Local Treatment of Helicobacter pylori Infections

Infections with Helicobacter pylori are a global challenge. Currently, H. pylori infections are treated systemically, but the eradication rates of the different therapy regimens are declining due to the growing number of bacterial strains resistant to major antibiotics. Here, we present a strategy for the local eradication of H. pylori by the use of Penicillin G sodium (PGS). In vitro experiments revealed that PGS shows high antibiotic activity against resistant strains of Helicobacter pylori with a minimum inhibitory concentration (MIC) of 0.125 μg/ml. In order to provide luminal concentrations above the MIC for longer periods of time, an extended release tablet was developed. Alkalizers were included to prevent acidic degradation of PGS within the tablet matrix. Out of the tested alkalizers MgO, l-Lysine, NaHCO3, and Na2CO3 NaHCO3 provided the strongest rise in pH inside the hydrated matrix when tested in simulated gastric fluid. Better PGS stability can mainly reasoned from that, addition of MgO resulted in high pH values within the matrix, causing basic degradation of PGS. This work is a first step towards the use of extended release tablets containing PGS for the local treatment of H. pylori as a safe and cost-effective alternative to common systemic treatment regimens.