Therapeutic Doses Of Drug Research Articles

Psychosomatic or Psychotropic Polypharmacy? A Case Highlighting the Importance of Pharmacokinetics

<h3>Introduction</h3> Psychotropic drugs are among the most common medications prescribed to elderly patients. The number of psychotropic drugs has increased significantly over the past few decades with a proportional increase in adverse medication outcomes including drug-drug interactions. Advancing age is accompanied by changes in pharmacokinetics and pharmacodynamics that put older patients at greater risk for adverse medication outcomes. The majority of psychotropic agents are metabolized by hepatic enzymes with many drug-drug interactions of psychotropics involving the cytochrome P450 enzyme system. The activity of these enzymes can be inhibited or induced by several drugs resulting in clinically significant drug-drug interactions. This case highlights the importance of maintaining a comprehensive understanding of pharmacokinetics and considering the possibility of an adverse drug reaction when evaluating an older patient presenting with new and unexplained symptoms. <h3>Methods</h3> This case report focuses on a geriatric patient with depression and multiple medical comorbidities presenting with unexplained neurological symptoms thought to be psychosomatic in origin. Patient's clinical documents in our electronic medical records system were reviewed. A literature survey was performed on the topic of psychotropic polypharmacy, pharmacokinetics, and the increased risk of adverse medical outcomes in geriatric patients. <h3>Results</h3> A 69 year old female was referred by inpatient neurology to an outpatient geriatric psychiatry clinic for evaluation and management of psychogenic non-epileptic seizures/conversion disorder. She had been experiencing ongoing symptoms of dizziness, dysarthria, and gait instability with multiple serious falls requiring hospitalization. She underwent an extensive and uneventful medical and neurological workup. Immediately prior to onset of symptoms, the patient was taking the maximum dose of amitriptyline at 150mg when bupropion was added and increased to 300mg. Symptoms were suspected to be secondary to amitriptyline toxicity with bupropion (a potent CYP2D6 inhibitor) leading to supratherapeutic amitriptyline levels (a CYP2D6 substrate). Amitriptyline level was obtained and returned supratherapeutic at 362. Both amitriptyline and bupropion were discontinued with immediate resolution of the patient's neurological symptoms. <h3>Conclusions</h3> Polypharmacy is a disease simulator; patients may exhibit conditions caused by medications rather than organic illness. It is crucial for clinicians to be aware of drug interactions and consider whether the development of a new medical condition could be the presentation of an adverse drug event. Many drug interactions are the result of altered CYP450 metabolism, and therapeutic drug doses may cause adverse effects related to increased drug serum levels if a CYP450 enzyme inhibitor is added or if the patient is a genetically poor metabolizer. Knowledge of the most important drugs metabolized by cytochrome P450 enzymes, as well as the most potent inducers and inhibitors, can help to reduce the occurrence of adverse drug events and interactions.

Interspecies Comparison and Radiation Effect on Pharmacokinetics of BIO 300, a Nanosuspension of Genistein, after Different Routes of Administration in Mice and Non-Human Primates.

BIO 300, a suspension of synthetic genistein nanoparticles, is being developed for mitigating the delayed effects of acute radiation exposure (DEARE). The purpose of the current study was to characterize the pharmacokinetic (PK) profile of BIO 300 administered as an oral or parenteral formulation 24 h after sham-irradiation, total-body irradiation (TBI) with 2.5-5.0% bone marrow sparing (TBI/BMx), or in nonirradiated sex-matched C57BL/6J mice and non-human primates (NHP). C57BL/6J mice were randomized to the following arms in two consecutive studies: sham-TBI [400 mg/kg, oral gavage (OG)], TBI/BM2.5 (400 mg/kg, OG), sham-TBI [200 mg/kg, subcutaneous (SC) injection], TBI/BM2.5 (200 mg/kg, SC), sham-TBI (100 mg/kg, SC), or nonirradiated [200 mg/kg, intramuscular (IM) injection]. The PK profile was also established in NHP exposed to TBI/BM5.0 (100 mg/kg, BID, OG). Genistein-aglycone serum concentrations were measured in all groups using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The PK profile demonstrates 11% and 19% reductions in Cmax and AUC0-inf, respectively, among mice administered 400 mg/kg, OG, after TBI/BM2.5 compared to the sham-TBI control arm. Administration of 200 mg/kg SC in mice exposed to TBI/BM2.5 showed a 53% increase in AUC0-inf but a 28% reduction in Cmax compared to the sham-TBI mice. The relative bioavailability of the OG route compared to the SC and IM routes in mice was 9% and 7%, respectively. After the OG route, the dose-normalized AUC0-inf was 13.37 (ng.h/mL)/(mg/kg) in TBI/BM2.5 mice compared to 6.95 (ng.h/mL)/(mg/kg) in TBI/BM5.0 NHPs. Linear regression of apparent clearances and weights of mice and NHPs yielded an allometric coefficient of 1.06. Based on these data, the effect of TBI/BMx on BIO 300 PK is considered minimal. Future studies should use SC and IM routes to maximize drug exposure when administered postirradiation. The allometric coefficient is useful in predicting therapeutic drug dose regimens across species for drug approval under the FDA animal rule.

Якість життя як показник ефективності комбінованої терапії з використанням транскраніальної магнітної стимуляції при епілепсії

У статті наводиться аналіз якості життя згідно з опитувальником QOLIE‑31 у 48 пацієнтів з епілепсією, яким здійснювалася ритмічна транскраніальна магнітна стимуляція (рТМС). Аналіз результатів проведеного дослідження з використанням рТМС і мінімальних терапевтичних доз антиепілептичних препаратів показав, що подібна комбінація фармакологічних і фізичних чинників дозволяє контролювати перебіг епілепсії та забезпечує досить високу протисудомну дію. Отримані результати дозволили обгрунтовано доповнити медикаментозне лікування епілепсії проведенням курсу рТМС, домогтися оптимального терапевтичного результату в кожного пацієнта з мінімальним ризиком побічних ефектів, а також поліпшити якість його життя.

Intracellular delivery of p53 gene and drug using cationised pullulan thiomer lowers the effective therapeutic doses of chemotherapeutic drug in cancer cells

One of the limitations associated with chemotherapy is the multidrug resistance in cancer cells. Hence higher doses are required for a therapeutic effect which lead to toxic effects. In order to address this problem, 3,3 dithiodipropionate modified pullulan, a cationic thiomer, is developed for delivery of p53 gene along with the drug doxorubicin and efflux pump inhibition. The aim is to induce synergistic effect of drug retention (Doxorubicin) and gene expression (p53) on cancer cells so as to achieve high cell death at lower drug doses. Transfection efficacy of apoptotic gene p53, drug retention kinetics, IC50, dose dependent effect of DOX on viability, influence of glutathione on drug retention and polymer mediated efflux pump inhibition were studied in different cell lines. The cationic thiomer proves to be a good transfecting agent and efflux pump inhibitor. The p53 expression, Pgp inihitory potential and drug retention could synergistically kill the cells and demonstrate very high cell death even at lower drug doses compared with drug alone thus proving the hypothesis.

Estimation of maximum recommended therapeutic dose of anti-retroviral drugs using diversified sampling and varied descriptors

article: Estimation of maximum recommended therapeutic dose of anti-retroviral drugs using diversified sampling and varied descriptors - Minerva Biotechnology and Biomolecular Research 2021 December;33(4):210-8 - Minerva Medica - Journals

A Hydrogel Ionic Circuit Based High-Intensity Iontophoresis Device for Intraocular Macromolecule and Nanoparticle Delivery.

Iontophoresis is an electrical-current-based, noninvasive drug-delivery technology, which is particularly suitable for intraocular drug delivery. Current ocular iontophoresis devices use low current intensities that significantly limit macromolecule and nanoparticle (NP) delivery efficiency. Increasing current intensity leads to ocular tissue damage. Here, an iontophoresis device based on a hydrogel ionic circuit (HIC), for high-efficiency intraocular macromolecule and NP delivery, is described. The HIC-based device is capable of minimizing Joule heating, effectively buffering electrochemical (EC) reaction-generated pH changes, and absorbing electrode overpotential-induced heating. As a result, the device allows safe application of high current intensities (up to 87mA cm-2 , more than 10 times higher than current ocular iontophoresis devices) to the eye with minimal ocular cell death and tissue damage. The high-intensity iontophoresis significantly enhances macromolecule and NP delivery to both the anterior and posterior segments by up to 300 times compared to the conventional iontophoresis. Therapeutically effective concentrations of bevacizumab and dexamethasone are delivered to target tissue compartments within 10-20min of iontophoresis application. This study highlights the significant safety enhancement enabled by an HIC-based device design and the potential of the device to deliver therapeutic doses of macromolecule and NP ophthalmic drugs within a clinically relevant time frame.

Label-free and highly sensitive nanoplasmonic biosensor-based autophagy flux sensing for clinical application

Autophagy is a cellular catabolic process that plays significant roles in various diseases such as neurodegenerative diseases, infectious diseases, and cancers. The importance of microtubule-associated protein 1 light chain 3 (LC3) quantification is highlighted because it is a precise tool for measuring autophagy and is also known to be associated with cancer progression, functioning as a clinically significant marker in cancer diagnosis and prognosis. To date, the quest continues to develop an autophagic LC3 detection method with enhanced sensitivity, and which provides a means of quantification to meet the clinical application needs. Here, we present a simple and intuitive autophagy flux measurement by a single gold nanoparticle-based LC3 sensing platform. This nanoplasmonic sensor does not require additional labeling, consisted of only gold nanorods and monoclonal antibodies, which enables rapid total LC3 quantification within a wide dynamic concentration range, with a detection limit of 64.1 fM. Moreover, the sensing ability of the proposed biosensor in cell lysates mimicking clinical samples and human cancer cell lysates was proved by providing a simple autophagic flux analysis method based on LSPR shifts. This sensor is the first label-free, highly sensitive total LC3 quantification nanoplasmonic biosensor that can be used for autophagy measurement, employed for precise cancer diagnosis in combination with other biomarkers. It can serve as an effective tool for determining therapeutic drug dosage in the future.

Natural Products Counteracting Cardiotoxicity during Cancer Chemotherapy: The Special Case of Doxorubicin, a Comprehensive Review.

Cardiotoxicity is a frequent undesirable phenomenon observed during oncological treatment that limits the therapeutic dose of antitumor drugs and thus may decrease the effectiveness of cancer eradication. Almost all antitumor drugs exhibit toxic properties towards cardiac muscle. One of the underlying causes of cardiotoxicity is the stimulation of oxidative stress by chemotherapy. This suggests that an appropriately designed diet or dietary supplements based on edible plants rich in antioxidants could decrease the toxicity of antitumor drugs and diminish the risk of cardiac failure. This comprehensive review compares the cardioprotective efficacy of edible plant extracts and foodborne phytochemicals whose beneficial activity was demonstrated in various models in vivo and in vitro. The studies selected for this review concentrated on a therapy frequently applied in cancer, anthracycline antibiotic—doxorubicin—as the oxidative stress- and cardiotoxicity-inducing agent.

Investigation of Substitution Reactions Between Zinc(II) Complexes with Different Geometries and N-Bonding Nucleophiles

Aims: The study aimed at investigating interactions between zinc(II) complexes with different geometrical structures and relevant nitrogen donor nucleophiles at physiological pH. Background: Lack of clear distinction between the therapeutic and toxic doses of platinum drugs is a major challenge for the design of novel non-platinum DNA and protein targeting metal-based anticancer agents. The non-platinum antitumor complexes could be alternatives to platinum-based drugs due to their better characteristics and different mechanisms of action. Objective: This study could provide more information regarding the design of future zinc-based anticancer drugs, providing a better understanding of the mechanism of interactions between Zn(II) complexes and nitrogen-donor nucleophiles (important from the medical point of view), and clarifying the changes in geometrical structures of zinc(II) that are referred to structure-reactivity correlations. Methods: Mole-ratio method and UV-V is spectroscopic kinetic method have been used. Results: The results indicated additional coordination of chlorides in the first coordination sphere with changes in coordination geometry and formation of the octahedral complex anion [ZnCl4(en)]2- while the excess of chloride did not affect the square-pyramidal structure of [ZnCl2(terpy)]. The substitutions of studied complexes and relevant nucleophiles proceeded in two consecutive reaction steps that depended on the nucleophile concentration. Octahedral complex anion [ZnCl4(en)]2- forms rapidly and all substitution processes of this complex species should be considered. We assume that the first reaction step is accompanied by the dissociation of chloride ligands. Nucleophile 1,2,4- triazoles have shown the highest affinity toward [ZnCl2(en)], and rates of both steps were almost of the same value, indicating parallel reactions. Conclusion: The different order of reactivity of relevant N-donor ligands toward [ZnCl2(en)] and [ZnCl2(terpy)] complexes for the first reaction step occurred because of the influence of different geometrical structures of complexes, while low reaction rates for the second reactions of [ZnCl2(en)] complex with imidazole and pyrazine were a consequence of interconversion between octahedral and tetrahedral structure during substitution processes.

ESTIMATION OF PREVALENCE OF ANAEMIA, VITAMIN B12, VITAMIN D &amp; FOLIC ACID DEFICIENCY IN FIRST YEAR MBBS STUDENTS OF A TERTIARY MEDICAL COLLEGE IN EASTERN INDIA

Medical students are more vulnerable to develop nutritional anemia ( i.e. haemoglobin, iron , vit B12, folate deciency) &amp; vitamin D deciency due to irregular eating habits &amp; hectic study schedule. Anemia among this age group has signicant health consequences ( e.g. poor cognition, decreased attention span , depressed immunity, repeated infections, increased fatigue etc) . So the present study was planned to ascertain the prevalence of anemia , iron , folic acid ,vit B12 &amp; D deciency among young adult female &amp; male st medical 1 year MBBS students of Medical College Kolkata,( batch 2019-2020) ,West Bengal,India and to suggest intervention strategies. 63 % &amp; 37% female &amp; male students respectively were found to be anaemic &amp; low level of hemoglobin is signicantly associated with type of family as 22% of study subject's belonged to joint family and 78% subjects belong to nuclear family. (p=0.002) &amp; there came out to be no signicant association between socio-economic status and anemia (p=0.213) . Among these subjects with anemia 12 had iron deciency . Serum folic acid levels were normal in the 100 study subjects . 30% students had low serum levels of vitamin B12 , and there was no gender preference (9 suffered from severe deciency, 21 students were in low normal range) . In this study, moderate Vitamin D deciency was found to be present in 42% subjects, mild insufciency in 57% subjects, and adequate serum Vitamin D levels in just 1%. Periodical and routine health check-up and haemoglobin estimation of the students at the time of entrance to Medical Colleges should be done. Iron and folic acid tablets and deworming drugs in therapeutic doses should be provided to the anaemic students. Students should be motivated and educated to take balanced diet, rich in green leafy vegetables and fruits.

Step-by-Step Design of New Theranostic Nanoformulations: Multifunctional Nanovectors for Radio-Chemo-Hyperthermic Therapy under Physical Targeting

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = −29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = −18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.

HIF-1α as a Target Molecule in the Use of Triazino-Indole Derivative on the Acoustic Trauma Model.

The effect of triazino-indole derivative (Trisan) on hypoxia-inducible factor (HIF) expression level in the organ of Corti, when administering it for therapeutic and preventive purposes, was investigated using an acoustic trauma model in experimental animals (female F1 hybrids of CBA and C57BL/6 lines). Cytoflavin was used as a comparator product. Study product Trisan (1% solution) was injected intravenously, intramuscularly and intraperitoneally, in the dose of 5, 7 and 10 mg/kg 2 h after the acoustic trauma for therapeutic purposes and in the dose of 5, 7 and 10 mg/kg for 3 days before the acoustic trauma for preventive purposes. IHC methods were used to investigate the organ of Corti. Trisan was observed to increase HIF expression in hair cells and neurons of the spiral ganglion in case of acoustic trauma. Depending on the dose, the increased HIF-1 expression in hair cells and spiral ganglion occurred both after therapeutic and preventive use of Trisan. Maximum HIF expression in hair cells and ganglion was noted at the therapeutic and preventive drug dose of 10 mg/kg. Following experimental results, we conclude that the otoprotective effect of triazino-indole derivative is realized via its effect on HIF metabolism, which makes it a target molecule for the drug.

The Treatment of Tuberculosis.

Tuberculosis (TB) remains a leading cause of infectious death worldwide, and poverty is a major driver. Clinically, TB presents as "latent" TB and active TB disease, and the treatment for each is different. TB drugs can display "early bactericidal activity (EBA)" and / or "sterilizing activity" (clearing persisters). Isoniazid is excellent at the former, and rifampin is excellent at the latter. Pyrazinamide and ethambutol complete the first-line regimen for drug-susceptible TB, each playing a specific role. Drug-resistant TB is an increasing concern, being met, in part, with repurposed drugs (including moxifloxacin, levofloxacin, linezolid, clofazimine, and beta-lactams) and new drugs (including bedaquiline, pretomanid, and delamanid). One challenge is to select drugs without overlapping adverse drug reaction profiles. QTc interval prolongation is one such concern, but to date, it has been manageable. Drug penetration into organism sanctuaries, such as the central nervous system, bone, and pulmonary TB cavities remain important challenges. The pharmacodynamics of most TB drugs can be described by the area under the curve (AUC) divided by the minimal inhibitory concentration (MIC). The hollow fiber infection model (HFIM) and various animal models (especially mouse and macaque) allow for sophisticated pharmacokinetic/pharmacodynamic experiments. These experiments may hasten the selection of the most potent, shortest possible regimens to treat even extremely drug resistant TB. These findings can be translated to humans by optimizing drug exposure in each patient, using therapeutic drug monitoring and dose individualization.

Cefiderocol in Critically Ill Patients with Multi-Drug Resistant Pathogens: Real-Life Data on Pharmacokinetics and Microbiological Surveillance.

Cefiderocol is a new siderophore-cephalosporin for the treatment of multi-drug resistant Gram-negative pathogens. As a reserve agent, it will and should be used primarily in critically ill patients in the upcoming years. Due to the novelty of the substance little data on the pharmacokinetics in critically ill patients with septic shock and renal failure (including continuous renal replacement therapy and cytokine adsorber therapy) is available. We performed therapeutic drug monitoring in a cohort of five patients treated with cefiderocol, to improve the knowledge on pharmacokinetics in this vulnerable patient population. As expected for a cephalosporin with predominantly renal elimination the maintenance dose could be reduced in patients with renal impairment or on continuous renal replacement therapy. The manufacturer’s dosing instructions were sufficient to achieve a drug level well above the MIC. However, the addition of a cytokine adsorber might reduce serum levels substantially, so that in this context therapeutic drug monitoring and dose adjustment are recommended.

In vitro and in vivo combinatorial anticancer effects of oxaliplatin- and resveratrol-loaded N,O-carboxymethyl chitosan nanoparticles against colorectal cancer

BackgroundOxaliplatin (OXE) combined with other chemotherapy drugs against colorectal cancer had been reported in the literature before, however, the efficacy of oxaliplatin combined with natural compounds was elusive. In addition, the clinical bioactivity and therapeutic dose of antitumor drugs are severely limited due to poor targeting and side effects. NDDSs offers an excellent strategy to overcome the disadvantages of small molecule anticancer drugs. MethodsHere, we have prepared N,O-carboxymethyl chitosan Oxaliplatin nanoparticles (CMCS-OXE NPs) and N,O-carboxymethyl chitosan Resveratrol nanoparticles (CMCS-Res NPs) were prepared by ion crosslinking and emulsification crosslinking, respectively. ResultsThe results revealed that the CMCS-OXE NPs exhibited a high encapsulation efficiency (60%) with a size of approximately 190.0 nm, and the CMCS-Res NPs exhibited a high encapsulation efficiency (65%) with a size of approximately 164.2 nm. The treatment with both types of nanoparticles combined exhibited more significant anti-colon cancer activity than the free drugs or either type of nanoparticle alone. In the in vivo experiments, the inhibition efficiency of the combined nanoparticle treatment was much stronger than the free drugs or either type of nanoparticle alone. ConclusionsOverall, combination of oxaliplatin and resveratrol into a nanoparticle-drug delivery systems (NDDSs) appears to be a promising strategy for colorectal cancer (CRC) therapy.

The role of Notch ligand, Delta-like ligand 4 (DLL4), in cancer angiogenesis—implications for therapy

Summary Background It is generally accepted that angiogenesis is a complex and tightly regulated process characterized by the growth of blood vessels from existing vasculature. Activation of the Notch signalling pathway affects multiple aspects of vascular development. One of the components of the Notch signalling pathway, Delta-like ligand 4 (DLL4), has recently appeared as a critical regulator of tumour angiogenesis and thus as a promising therapeutic target. Methods This review article includes available data from peer-reviewed publications associated with the role of DLL4 in cancer angiogenesis. Searches were performed in PubMed, EMBASE, Google Scholar and Web of Science using the terms “tumour angiogenesis”, “DLL4”, “Notch signalling” and “anti-cancer therapy”. Results The survival curves of cancer patients revealed that the patients with high DLL4 expression levels had significantly shorter survival times than the patients with low DLL4 expression. Moreover, a positive correlation was also identified between DLL4 and VEGF receptorsʼ expression levels. It seems that inhibition of DLL4 may exert potent growth inhibitory effects on some tumours resistant to anti-VEGF therapies. A great number of blocking agents of DLL4/Notch signalling including anti-DLL4 antibodies, DNA vaccination, Notch antibodies and gamma-secretase inhibitors have been studied in preclinical tumour models. Conclusion DLL4 seems to be a promising target in anti-cancer therapy. Nevertheless, the careful evaluation of adverse effects on normal physiological processes in relation to therapeutic doses of anti-DLL4 drugs will be significant for advancement of DLL4 blocking agents in clinical oncology.

Measurement of the Antipsychotic Clozapine Using Reduced Graphene Oxide Nanocomposites‐Au/Pd/Pt Electrodes

AbstractEnhanced methods of drug monitoring are required to support the individualization of therapeutic drug dosing. Clozapine is one of the most important medications for managing schizophrenia, and timely measurement of serum clozapine levels has been identified as a barrier to the broader use of clozapine. For the first time, reduced graphene oxide nanocomposites were used to construct an electrochemical clozapine (Clz) sensor. The Reduced graphene oxide (Rego) nanocomposites were synthesized and characterized by using X‐Ray Diffraction (XRD), Fourier‐Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM) techniques. The Clz sensing electrode was fabricated by drop coating of Rego nanocomposites suspension and Nafion solution on the pencil graphite electrode, respectively. The electrochemical behavior and influence of various physicochemical parameters of sensing electrodes were investigated by using cyclic voltammetry (CV) and differential voltammetry (DPV) techniques. The designed sensor displayed decent linear range, detection limit, reproducibility, and reusability results. Under optimum experimental parameters a linear dynamic range of 0.05–10 μM clozapine was observed with actual detection limit of 50 nM. Furthermore, the designed sensing electrode was used to measure the amount of Clz in real samples.

Mucoadhesive Gelatin Buccal Films with Propranolol Hydrochloride: Evaluation of Mechanical, Mucoadhesive, and Biopharmaceutical Properties.

This study processes and characterizes propranolol hydrochloride/gelatin mucoadhesive buccal films. Two types of gelatin are used: Gelatin from porcine skin, type A (GA), and gelatin from bovine skin (GB). The influence of gelatin type on mechanical, mucoadhesive, and biopharmaceutical characteristics of buccal films is evaluated. Fourier-Transfer infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analysis show that GA with propranolol hydrochloride (PRH) in the film (GAP) formed a physical mixture, whereas GB with PRH (GBP) form a compound-complex. Results of mechanical testing (tensile test, hardness) revealed that GAP films exhibit higher elastic modulus, tensile strength, and hardness. A mucoahesion test shows that GBP has higher adhesion strength, while GAP shows higher work of adhesion. Both in vitro release study and in silico simulation indicated that processed films can provide effective drug transport through the buccal mucosa. In silico simulation shows improved bioavailability from buccal films, in comparison to the immediate-release tablets—indicating that the therapeutic drug dose can be markedly reduced.

Steering a Course through the COVID-19 Pandemic: Should the SECURE-IBD Registry Influence Prescribing for Patients with Inflammatory Bowel Disease?

Summary The global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, also referred to as COVID-19) rapidly became an unprecedented healthcare challenge. It represents a particular concern for patients with inflammatory bowel disease (IBD), many of whom require treatment with immunosuppressive medication which may be associated with an increased risk of both viral and bacterial infections (Gastroenterology 2018;155(2):337-346.e10). Moreover, as IBD is a lifelong condition, patients are frequently older with comorbidities, further increasing the potential risks of a more severe COVID-19 disease course. This has led to considerable uncertainty over appropriate treatment of IBD in the COVID-19 era, and has brought safety considerations into the focus of the patients and physicians.

Osteoarthritis In Vitro Models: Applications and Implications in Development of Intra-Articular Drug Delivery Systems.

Osteoarthritis (OA) is a complex multi-target disease with an unmet medical need for the development of therapies that slow and potentially revert disease progression. Intra-articular (IA) delivery has seen a surge in osteoarthritis research in recent years. As local administration of molecules, this represents a way to circumvent systemic drug delivery struggles. When developing intra-articular formulations, the main goals are a sustained and controlled release of therapeutic drug doses, taking into account carrier choice, drug molecule, and articular joint tissue target. Therefore, the selection of models is critical when developing local administration formulation in terms of accurate outcome assessment, target and off-target effects and relevant translation to in vivo. The current review highlights the applications of OA in vitro models in the development of IA formulation by means of exploring their advantages and disadvantages. In vitro models are essential in studies of OA molecular pathways, understanding drug and target interactions, assessing cytotoxicity of carriers and drug molecules, and predicting in vivo behaviors. However, further understanding of molecular and tissue-specific intricacies of cellular models for 2D and 3D needs improvement to accurately portray in vivo conditions.