Effects of excipients on the interactions of self-emulsifying drug delivery systems with human blood plasma and plasma membranes.

Due to its versatility in formulation and manufacturing, self-emulsifying drug delivery systems (SEDDS) can be used to design parenteral formulations. Therefore, it is necessary to understand the effects of excipients on the behavior of SEDDS formulations upon parenteral administration, particularly their interactions with blood plasma and cell membranes. In this study, we prepared three neutrally charged SEDDS formulations composed of medium-chain triglycerides as the oil phase, polyoxyl-35 castor oil (EL35) and polyethylene glycol (15)-hydroxystearate (HS15) as the nonionic surfactants, medium-chain mono- and diglycerides as the co-surfactant, and propylene glycol as the co-solvent.

Magnetic Activated Carbon from ZnCl and FeCl Coactivation of Lotus Seedpod: One-Pot Preparation, Characterization, and Catalytic Activity towards Robust Degradation of Acid Orange 10.

Lotus seedpods (LSPs) are an abundant and underutilized agricultural residue discarded from lotus seed production. In this study, ZnCl and FeCl coactivation of LSP for one-pot preparation of magnetic activated carbon (MAC) was explored for the first time. X-ray diffraction XRD) results showed that FeO, Fe, and ZnO crystals were formed in the LSP-derived carbon matrix.

Collaborative Referral Model for Hepatitis C Screening and Treatment in a Remote Mountainous Region of Taiwan during the COVID-19 Pandemic.

Community-based screening for the hepatitis C virus (HCV) decreased during the COVID-19 pandemic. We developed a collaborative referral model between a primary clinic (Liouguei District Public Health Center, LDPHC) and a tertiary referral center to increase HCV screening and treatment uptake in a mountainous region of Taiwan. Once-in-a-lifetime hepatitis B and C screening services established by the Taiwan National Health Insurance were performed at LDPHC.

A Phase 1/2 Study of Rapamycin and Cisplatin/Gemcitabine for Treatment of Patients With Muscle-Invasive Bladder Cancer.

Introduction: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard for muscle-invasive bladder cancer (MIBC), however, NAC confers only a small survival benefit and new strategies are needed to increase its efficacy. Pre-clinical data suggest that in response to DNA damage the tumor microenvironment (TME) adopts a paracrine secretory phenotype dependent on mTOR signaling which may provide an escape mechanism for tumor resistance, thus offering an opportunity to increase NAC effectiveness with mTOR blockade.

Patients & Methods: We conducted a phase I/II clinical trial to assess the safety and efficacy of gemcitabine-cisplatin-rapamycin combination.

A reanalysis of pain crises data from the pivotal l-glutamine in sickle cell disease trial.

The pivotal Endari trial in sickle cell disease showed a reduction in pain crises events. This reanalysis of the l-glutamine phase 3 trial using annual rates of pain crises, consistent with other SCD studies, supported the statistically significant outcomes of the original analysis. The observed 45% difference in the VOC rate is comparable to what was reported in other sickle cell therapeutics used to reduce the incidence of pain.

Relationship between plumage color and eggshell patterns with egg production and egg quality traits of Japanese quails.

Aim: This study was conducted to identify the diversity of feather color and to determine the relationship between plumage color and egg yield as well as eggshell patterns and internal egg quality traits of Japanese quails.

Materials And Methods: For investigating phenotypic diversity, a total of 600 quails from five breeding farms were evaluated to record head feather, shank, and plumage color. An on-station experiment was also conducted on 360 laying quails to examine the relationship between plumage color and egg production and egg weight during 24 weeks of laying.

Mucolytic self-emulsifying drug delivery systems (SEDDS) containing a hydrophobic ion-pair of proteinase.

Aim: The aim of this study was to form hydrophobic ion-pairs of proteinase with cationic surfactants and to incorporate them into self-emulsifying drug delivery systems (SEDDS) to improve their mucus permeating properties.

Methods: Proteinase was ion-paired with benzalkonium chloride (BAK), hexadecylpyridinium chloride (HDP), alkyltrimethylammonium bromide (ATA) and hexadecyltrimethylammonium bromide (HDT) at pH 8.5-9.

Meta-analytical methods for estimating outcomes from overall response rate in patients with relapsed/refractory diffuse large B-cell lymphoma.

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is highly heterogeneous and current trials are investigating new approaches to improve outcomes. Limited data on response endpoints can confound estimation of a treatment effect when designing studies of novel agents in this setting, which can hinder study sample size calculations, especially if a net estimate is required for a 'physician's choice' comparator arm. Here we estimate complete response rate (CRR), overall response rate (ORR), and extrapolate durable response rates (DRR; CR/partial response lasting ≥16 weeks) for such a comparator arm from published ORRs in DLBCL.

Self-emulsifying drug delivery systems and cationic surfactants: do they potentiate each other in cytotoxicity?

Objectives: The aim of this study was to evaluate the cytotoxicity of self-emulsifying drug delivery systems (SEDDS) containing five different cationic surfactants.

Methods: Cationic surfactants were added in a concentration of 1% and 5% (m/m) to SEDDS comprising 30% Capmul MCM, 30% Captex 355, 30% Cremophor EL and 10% propylene glycol. The resulting formulations were characterized in terms of size, zeta potential, in-vitro haemolytic activity and toxicity on Caco-2 via MTT assay and lactate dehydrogenase release assay.

Hepatocellular differentiation status is characterized by distinct subnuclear localization and form of the chanzyme TRPM7.

The channel-kinase TRPM7 is important for the survival, proliferation, and differentiation, of many cell types. Both plasma membrane channel activity and kinase function are implicated in these roles. Channel activity is greater in less differentiated hepatoma cells compared with non-dividing, terminally differentiated adult hepatocytes, suggesting differences in protein expression and/or localization.

Thiomers: Impact of in situ cross-linkers on mucoadhesive properties.

The aim of this study was to evaluate the impact of in situ cross-linkers on the gelling and mucoadhesive properties of thiomers. Polycarbophil-cysteine conjugate (PCP-cys) was synthesized by covalent attachment of l-cysteine to polycarbophil via amide bond formation mediated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) and N-hydroxysuccinimide (NHS) whereas in situ cross-linkers (PAA-cys-MNA) were synthesized by the same bond formation between poly(acrylic acid) (PAA) of 2.1-, 6-, and 15kDa and 2-((2-amino-2-carboxyethyl)disulfanyl)nicotinic acid (cys-MNA) used as ligand.

Storage Stability of Bivalirudin: Hydrophilic Versus Lipophilic Solutions.

It was the aim of this study to incorporate a model peptide bivalirudin in self-emulsifying drug delivery system (SEDDS) and compare its storage stability with conventional aqueous solutions. Firstly, bivalirudin lipophilicity was increased via hydrophobic ion pairing using anionic or cationic surfactants. The chosen bivalirudin docusate complex (BIV/AOT) was incorporated into SEDDS composed of 40% (w/w) Cremophor EL, 20% (w/w) Capmul PG-8, and 40% (w/w) propylene glycol with a drug payload of 0.

Improved mucoadhesive properties of self-nanoemulsifying drug delivery systems (SNEDDS) by introducing acyl chitosan.

This study was aimed to improve the mucoadhesive properties of SNEDDS by the incorporation of acyl chitosan including octanoyl chitosan (OC), lauroyl chitosan (LC) and palmitoyl chitosan (PC). SNEDDS and acyl chitosan SNEDDS were characterized regarding droplet size and zeta potential. Their mucoadhesivity on porcine intestinal mucosa was evaluated by falling liquid film technique using Sudan Red G as marker.

Effect of l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine on ischemic heart disease risk: A Mendelian randomization study.

Background: l-arginine is a commonly consumed dietary conditional essential amino acid found in food items and supplements, which is closely related to asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). l-arginine is thought to increase nitric oxide and be cardioprotective, whereas ADMA and SDMA may inhibit nitric oxide synthesis and increase cardiovascular disease risk. Unexpectedly, l-arginine increased mortality in a small trial.

Self-emulsifying drug delivery systems (SEDDS): Proof-of-concept how to make them mucoadhesive.

Aim: The objective of this study was to provide a proof-of-concept that self-emulsifying drug delivery systems can be made mucoadhesive by the incorporation of hydrophobic mucoadhesive polymers.

Methods: In order to obtain such a hydrophobic mucoadhesive polymer, Eudragit® S100 was thiolated by covalent attachment of cysteamine. After determination of the thiol group content, in vitro mucoadhesion studies (rotating cylinder and rheological measurements) were performed.

Preactivated thiolated pullulan as a versatile excipient for mucosal drug targeting.

Aim: The purpose of the present study was to generate a novel mucoadhesive thiolated pullulan with protected thiol moieties and to evaluate its suitability as mucosal drug delivery system.

Methods: Two different synthetic pathways: bromination-nucleophilic substitution and reductive amination including periodate cleavage were utilized to synthesize such thiolated pullulans. The thiomer (pullulan-cysteamine) with the highest amount of free thiol groups was further enrolled in a reaction with 6-mercaptonicotinamide and its presence in pullulan structure was confirmed via NMR analysis.

Development and in vitro evaluation of zeta potential changing self-emulsifying drug delivery systems for enhanced mucus permeation.

The aim of this study was the development of zeta potential changing self-emulsifying drug delivery systems (SEDDS). Various cationic surfactants were incorporated into a formulation consisting of 30% Cremophor EL, 30% Capmul MCM, 30% Captex 355 and 10% propylene glycol (w/w). A substrate of intestinal alkaline phosphatase (IAP), 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid sodium (PA), was thereafter incorporated into SEDDS.

Development and in vitro evaluation of an oral SEDDS for desmopressin.

Context: Self-emulsifying drug delivery systems (SEDDS) are among most promising tools for improving oral peptide bioavailability.

Objective: In this study, in vitro protective effect of SEDDS containing desmopressin against presystemic inactivation by glutathione and α-chymotrypsin was evaluated.

Materials And Methods: The partitioning coefficient (log P) of desmopressin was increased via hydrophobic ion pairing using anionic surfactants.

Recent Patents of Complementary and Alternative Medicine for Allergic Rhinitis.

Allergic rhinitis (AR) is a common respiratory disease affecting both adults and children worldwide. Affected patients may experience nasal congestion/stuffiness, rhinorrhea (anterior and/or posterior), nasal/ nasopharyngeal itching and sneezing. Allergen avoidance is the principal step in the management.

Development and in vitro characterisation of an oral self-emulsifying delivery system for daptomycin.

It was the aim of this study to develop an oral self-emulsifying drug delivery system (SEDDS) for the peptide drug daptomycin exhibiting an anionic net charge. Drug lipophilicity was increased by hydrophobic ion pairing with cationic surfactant dodecylamine hydrochloride in molar ratio of surfactant to peptide 5:1. Log P (octanol/water) of -5.

Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial.

Background: The EXAMINE trial showed non-inferiority of the DPP-4 inhibitor alogliptin to placebo on major adverse cardiac event (MACE) rates in patients with type 2 diabetes and recent acute coronary syndromes. Concerns about excessive rates of in-hospital heart failure in another DPP-4 inhibitor trial have been reported. We therefore assessed hospital admission for heart failure in the EXAMINE trial.

Compounds that correct F508del-CFTR trafficking can also correct other protein trafficking diseases: an in vitro study using cell lines.

Background: Many genetic diseases are due to defects in protein trafficking where the mutant protein is recognized by the quality control systems, retained in the endoplasmic reticulum (ER), and degraded by the proteasome. In many cases, the mutant protein retains function if it can be trafficked to its proper cellular location. We have identified structurally diverse correctors that restore the trafficking and function of the most common mutation causing cystic fibrosis, F508del-CFTR.

Differential expression of TRPM7 in rat hepatoma and embryonic and adult hepatocytes.

TRPM7 channels are implicated in cellular survival, proliferation, and differentiation. However, a profile of TRPM7 activity in a specific cell type has not been determined from embryonic to terminally differentiated state. Here, we characterized TRPM7 expression in a spectrum of rat liver cells at different developmental stages.

Dual optical sensor for oxygen and temperature based on the combination of time domain and frequency domain techniques.

In measuring specific conditions in the real world, there are many situations where both the oxygen concentration and the temperature have to be determined simultaneously. Here we describe a dual optical sensor for oxygen and temperature that can be adapted for different applications. The measurement principle of this sensor is based on the luminescence decay times of the oxygen-sensitive ruthenium complex tris-4,7-diphenyl-1,10-phenanthroline ruthenium(III) [Rudpp] and the temperature-sensitive europium complex tris(dibenzoylmethane) mono(5-amino-1,10-phenanthroline)europium(III) [Eudatp].