TSPO-targeted NIR-fluorescent ultra-small iron oxide nanoparticles for glioblastoma imaging.
Abstract The translocator protein 18 kDa (TSPO) is mainly located in outer membrane of mitochondria and results highly expressed in a variety of tumor including breast, colon, prostate, ovarian and brain (such as glioblastoma). Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor. Although GBM patients had currently available therapies, the median survival is
Source: European Journal of Pharmaceutical Sciences - August 15, 2019 Category: Drugs & Pharmacology Authors: Denora N, Lee C, Iacobazzi RM, Choi JY, Song IH, Yoo JS, Piao Y, Lopalco A, Leonetti F, Lee BC, Kim SE Tags: Eur J Pharm Sci Source Type: research

Design, synthesis and anticancer evaluation of novel 1,3-benzodioxoles and 1,4-benzodioxines.
Abstract A new set of 1,3-benzodioxoles and 1,4-benzodioxines was designed and synthesized starting from gallic acid as anticancer agents. The antiproliferative effect of the target compounds was evaluated against a panel of cancer cell lines (HepG2, PC-3, MCF-7 and A549) using MTT assay. The 1,4-benzodioxine derivative 11a manifested broad spectrum effect towards the four tested cancer cell lines (IC50 
Source: European Journal of Pharmaceutical Sciences - August 14, 2019 Category: Drugs & Pharmacology Authors: Hassan RM, Abd-Allah WH, Salman AM, El-Azzouny AA, Aboul-Enein MN Tags: Eur J Pharm Sci Source Type: research

Design, synthesis, biological evaluation and molecular docking study of arylcarboxamido piperidine and piperazine-based hydroxamates as potential HDAC8 inhibitors with promising anticancer activity.
Abstract HDAC8 has been established as one of the vital targets as far as the cancer is concerned. Different compounds having potential HDAC inhibitory activity have been approved by USFDA. However, none of these compounds are selective towards specific HDAC isoform. In this current study, some new hydroxamate derivatives with alkylpiperidine and alkylpiperazine linker moieties have been designed, synthesized and biologically evaluated. All these compounds are effective HDAC8 inhibitors comprising more or less similar cytotoxic potential against different cancer cell lines. It is observed that the piperazine scaff...
Source: European Journal of Pharmaceutical Sciences - August 14, 2019 Category: Drugs & Pharmacology Authors: Trivedi P, Adhikari N, Amin SA, Bobde Y, Ganesh R, Jha T, Ghosh B Tags: Eur J Pharm Sci Source Type: research

A novel in vivo predictive dissolution testing coupled with a modeling and simulation for hydrogel matrix monolithic extended release oral dosage forms.
The objective of this research was to design a novel in vitro dissolution testing for hydrogel matrix monolithic extended release tablets, in which physiologically relevant conditions of swelling, stress, and erosion for the tablets in the fasted gastrointestinal tract are taken into consideration. Mirabegron extended release tablets (three variations) were used as model formulations in this research. In in vitro dissolution testing, the tablets were allowed to swell in 10 mL of dissolution medium, after which they were stressed under a pressure of ca. 300 g/cm2 and then allowed to erode in a very limited volume of int...
Source: European Journal of Pharmaceutical Sciences - August 14, 2019 Category: Drugs & Pharmacology Authors: Kambayashi A, Dressman JB Tags: Eur J Pharm Sci Source Type: research

Exploration of supersaturable lacidipine ternary amorphous solid dispersion for enhanced dissolution and in vivo absorption.
In conclusion, the presented SDS could not only be regarded as solubility enhancer but also dissolution or bioavailability promoter, highlighting its potential application in ternary supersaturable amorphous solid dispersion for further increasing the dissolution and in vivo absorption of poorly water soluble drugs. PMID: 31415903 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - August 12, 2019 Category: Drugs & Pharmacology Authors: Guan J, Jin L, Liu Q, Xu H, Wu H, Zhang X, Mao S Tags: Eur J Pharm Sci Source Type: research

Pharmacokinetic profile and safety of intravenous NEPA, a fixed combination of fosnetupitant and palonosetron, in cancer patients: Prevention of chemotherapy-induced nausea and vomiting associated with highly emetogenic chemotherapy.
This study evaluated the pharmacokinetics and safety of i.v. NEPA in cancer patients. This was a single-center, single-dose phase 1 study in patients receiving highly emetogenic chemotherapy. Patients received a 30-min infusion of i.v. NEPA plus oral dexamethasone (12 mg) prior to chemotherapy, and oral dexamethasone (8 mg/daily) on days 2-4. Twenty-four patients received the complete i.v. NEPA infusion volume. Fosnetupitant maximum plasma concentration (Cmax) was reached at the end of infusion and decreased to
Source: European Journal of Pharmaceutical Sciences - August 9, 2019 Category: Drugs & Pharmacology Authors: Kurteva G, Chilingirova N, Rizzi G, Caccia T, Stella V, Bernareggi A Tags: Eur J Pharm Sci Source Type: research

Comparison of liquid chromatography-mass spectrometry and direct infusion microchip electrospray ionization mass spectrometry in global metabolomics of cell samples.
In this study, the feasibility of direct infusion electrospray ionization microchip mass spectrometry (chip-MS) was compared to the commonly used liquid chromatography-mass spectrometry (LC-MS) in non-targeted metabolomics analysis of human foreskin fibroblasts (HFF) and human induced pluripotent stem cells (hiPSC) reprogrammed from HFF. The total number of the detected features with chip-MS and LC-MS were 619 and 1959, respectively. Approximately 25% of detected features showed statistically significant changes between the cell lines with both analytical methods. The results show that chip-MS is a rapid and simple method ...
Source: European Journal of Pharmaceutical Sciences - August 9, 2019 Category: Drugs & Pharmacology Authors: Pöhö P, Lipponen K, Bespalov MM, Sikanen T, Kotiaho T, Kostiainen R Tags: Eur J Pharm Sci Source Type: research

Inhibitory effects of selected antibiotics on the activities of α-amylase and α-glucosidase: In-vitro, in-vivo and theoretical studies.
Inhibitory effects of selected antibiotics on the activities of α-amylase and α-glucosidase: In-vitro, in-vivo and theoretical studies. Eur J Pharm Sci. 2019 Aug 07;:105040 Authors: Amiri B, Hosseini NS, Taktaz F, Amini K, Rahmani M, Amiri M, Sadrjavadi K, Jangholi A, Esmaeili S Abstract Antibiotics are effective drugs that are used to treat infectious diseases either by killing bacteria or slowing down their growth. The well-adapted structural features of antibiotics for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible ba...
Source: European Journal of Pharmaceutical Sciences - August 7, 2019 Category: Drugs & Pharmacology Authors: Amiri B, Hosseini NS, Taktaz F, Amini K, Rahmani M, Amiri M, Sadrjavadi K, Jangholi A, Esmaeili S Tags: Eur J Pharm Sci Source Type: research

Antioxidant properties of probucol released from mesoporous silica.
Abstract Antioxidants play a vital role in scavenging reactive oxygen species (ROS) produced by the reduction of molecular oxygen from various cellular mechanisms. Under oxidative stress, an increase in the levels of ROS overwhelms the antioxidant response, causing oxidative damage to biological molecules, and leading to the development of various diseases. Drug compounds with potent antioxidant properties are typically poorly water soluble and highly hydrophobic. An extreme case is Probucol (PB), a potent antioxidant with reported water solubility of 5 ng/ml, and oral bioavailiability of
Source: European Journal of Pharmaceutical Sciences - August 6, 2019 Category: Drugs & Pharmacology Authors: Lau M, Giri K, Garcia-Bennett AE Tags: Eur J Pharm Sci Source Type: research

Development and optimization of a novel PLGA-Levan based drug delivery system for curcumin, using a quality-by-design approach.
In conclusion, this study was an effort for developing a DDS which solubilizes Curcumin in clinically applicable concentrations. PMID: 31394257 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - August 5, 2019 Category: Drugs & Pharmacology Authors: Bahadori F, Eskandari Z, Ebrahimi N, Bostan MS, Eroğlu MS, Oner ET Tags: Eur J Pharm Sci Source Type: research

A systems pharmacokinetic/pharmacodynamic model for concizumab to explore the potential of anti-TFPI recycling antibodies.
Abstract Concizumab is a humanized monoclonal antibody in clinical investigation directed against membrane-bound and soluble tissue factor pathway inhibitor (mTFPI and sTFPI) for treatment of hemophilia. Concizumab displays a non-linear pharmacokinetic (PK) profile due to mTFPI-mediated endocytosis and necessitates a high dose and frequent dosing to suppress the abundant sTFPI, a negative regulator of coagulation. Recycling antibodies that can dissociate bound mTFPI/sTFPI in endosomes for degradation and rescue antibody from degradation have a potential in reducing the dose by extending antibody systemic persisten...
Source: European Journal of Pharmaceutical Sciences - August 5, 2019 Category: Drugs & Pharmacology Authors: Yuan D, Rode F, Cao Y Tags: Eur J Pharm Sci Source Type: research

BRD4 PROTAC as a novel therapeutic approach for the treatment of vemurafenib resistant melanoma: Preformulation studies, formulation development and in vitro evaluation.
Abstract Limited therapeutic interventions and development of resistance to targeted therapy within few months of therapy pose a great challenge in the treatment of melanoma. Current work was aimed to investigate; (a) Anticancer activity of a novel class of compound - Bromodomain and Extra-Terminal motif (BET) protein degrader in sensitive and vemurafenib-resistant melanoma (b) Preformulation studies and formulation development. ARV-825 (ARV), a molecule designed using PROteolysis-TArgeting Chimeric (PROTAC) technology, degrades BRD4 protein instead of merely inhibiting it. Based on extensive preformulation studie...
Source: European Journal of Pharmaceutical Sciences - August 5, 2019 Category: Drugs & Pharmacology Authors: Rathod D, Fu Y, Patel K Tags: Eur J Pharm Sci Source Type: research

Pharmacokinetics and hemorheology of phosphocreatine and creatine in rabbits: A directly comparative study between parent drug and active metabolite.
This study is to investigate pharmacokinetics (PK) and hemorheology (HR) of exogenous phosphocreatine (PCr), a cardio-protective agent, and its active metabolite creatine (Cr), with particular focus on the PK and PD comparison between PCr and Cr. A specific ion-pair reversed-phase HPLC-UV assay was used to simultaneously measure PCr, Cr and ATP concentrations in plasma and red blood cells (RBC) samples of rabbits. PK and HR parameters were calculated based on concentration-time (C-T) curves and effect-time (E-T) curves, respectively, obtained after i.v. dosing. Meanwhile the apparent pharmacological activity ratio (Rapp) a...
Source: European Journal of Pharmaceutical Sciences - August 2, 2019 Category: Drugs & Pharmacology Authors: Xi H, Zhang A, Han G, Li C, Lv L Tags: Eur J Pharm Sci Source Type: research

NLG919/cyclodextrin complexation and anti-cancer therapeutic benefit as a potential immunotherapy in combination with paclitaxel.
In this study a cyclodextrin (CD) complexation strategy has been systematically evaluated to achieve a simple and feasible method to prepare a NLG919 injectable formulation. From a series of CDs, HP-β-CD proved to be the most conducive for NLG919 solubilization (approx 800-fold increase). Characterization studies using DSC, 1H NMR, XRPD and molecular simulation demonstrated that the NLG919/HP-β-CD loading mechanism involved an increasing pH-dependent binding affinity. Importantly cell-based studies in vitro and anti-tumour activity in vivo demonstrated that the pharmacological activity of NLG919 as an IDO-1 inhib...
Source: European Journal of Pharmaceutical Sciences - August 2, 2019 Category: Drugs & Pharmacology Authors: Xu J, Ren X, Guo T, Sun X, Chen X, Patterson LH, Li H, Zhang J Tags: Eur J Pharm Sci Source Type: research

Sustained-release microparticle dry powders of chloramphenicol palmitate or thiamphenicol palmitate prodrugs for lung delivery as aerosols.
Abstract The purpose of this study was to design inhalable sustained-release nanoparticle-in-microparticles, i.e. nano-embedded microparticles, for the lung delivery of chloramphenicol or thiamphenicol as aerosols. The palmitate ester prodrugs of the two antibiotics were used to prepare PLGA-based nanoparticles or to form pure prodrug nanoparticles. Prodrug-loaded PLGA nanoparticles or pure prodrug nanoparticles were prepared using the emulsion-solvent evaporation method. Dry microparticle powders for inhalation were then produced by spray-drying the nanoparticle suspensions supplemented with lactose as a bulking ...
Source: European Journal of Pharmaceutical Sciences - August 1, 2019 Category: Drugs & Pharmacology Authors: Nurbaeti SN, Brillault J, Tewes F, Olivier JC Tags: Eur J Pharm Sci Source Type: research

Self microemulsifying drug delivery system of lurasidone hydrochloride for enhanced oral bioavailability by lymphatic targeting: In vitro, Caco-2 cell line and in vivo evaluation.
Abstract The global aim of this research was to develop and evaluate self-microemulsifying drug delivery system (SMEDDS) to improve oral bioavailability of Lurasidone Hydrochloride (LH). A chylomicron flow blocking approach was used to evaluate lymphatic drug transport. The developed LH-SMEDDS composed of Capmul MCM C8 (oil), Cremophor EL (surfactant) and Transcutol HP (co-surfactant). Highest microemulsifying area was obtained at 3:1 ratio (surfactant:cosurfactant)and mean globule size was found to be 49.22 ± 1.60 nm. More than 98% drug release was obtained with LH-SMEDDS as that of LH suspension. Co...
Source: European Journal of Pharmaceutical Sciences - August 1, 2019 Category: Drugs & Pharmacology Authors: Patel MH, Sawant KK Tags: Eur J Pharm Sci Source Type: research

Enteric coating of oral solid dosage forms as a tool to improve drug bioavailability.
Abstract Enteric coating is a common procedure in the development of oral pharmaceutical dosage forms. The main advantage of enteric coating is that it protects the drug from acidic pH and enzymatic degradation in the stomach while protecting it from the undesirable effects of some drugs. There is certain controversy regarding the real influence of enteric coating on the bioavailability of many drugs. Various scientific articles have demonstrated an improvement in the extent of bioavailability of some drugs when enteric coating is used. In recent years, there have been many studies examining different formulation ...
Source: European Journal of Pharmaceutical Sciences - July 30, 2019 Category: Drugs & Pharmacology Authors: Maderuelo C, Lanao JM, Zarzuelo A Tags: Eur J Pharm Sci Source Type: research

Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes.
no MP Abstract The aim of this work was to clarify the dynamics behind the influence of ionic strength on the changes in drug release from large unilamellar vesicles (LUVs). For this purpose, we have investigated the transport of two different model drugs (caffeine and hydrocortisone) formulated into liposomes through different types of barriers with different retention properties (regenerated cellulose and the newly introduced biomimetic barrier, Permeapad®). Drug release from liposomes was studied utilizing the standard Franz diffusion cells. LUV dispersions were exposed to the isotonic, hypotonic and hypert...
Source: European Journal of Pharmaceutical Sciences - July 30, 2019 Category: Drugs & Pharmacology Authors: Wu IY, Bala S, Škalko-Basnet N, di Cagno MP Tags: Eur J Pharm Sci Source Type: research

Tannic acid as a precipitating agent of human plasma proteins.
In this study, TA-plasma protein complexes were studied at different pH conditions, tannin/plasma ratio and reaction mixing time. The complexes formed from combinations of TA and plasma proteins were analyzed by gel electrophoresis, protein quantification, particle size, charge, mass spectrometry, microscopic image, and circular dichroism. It was possible to verify the precipitate formation in all tested pH values, with high precipitation at pH 5. The native PAGE analysis showed three mainly bands corresponding independent of the pHs used. It was possible to observe a gradual growing of precipitate protein in the first p...
Source: European Journal of Pharmaceutical Sciences - July 29, 2019 Category: Drugs & Pharmacology Authors: Pinto AF, do Nascimento JM, da Silva Sobral RV, de Amorim ELC, Silva RO, Leite ACL Tags: Eur J Pharm Sci Source Type: research

Biosensor-based kinetic and thermodynamic characterization of opioids interaction with human μ-opioid receptor.
Biosensor-based kinetic and thermodynamic characterization of opioids interaction with human μ-opioid receptor. Eur J Pharm Sci. 2019 Jul 26;:105017 Authors: Babazada H, Alekberli T, Hajieva P, Farajov E Abstract Development of opioid analgesics with minimal side effects requires substantial knowledge on structure-kinetic and -thermodynamic relationship of opioid-receptor interactions. Here, combined kinetics and thermodynamics of opioid agonist binding to human μ-opioid receptor (h-μOR) was investigated using real-time label-free surface plasmon resonance (SPR)-based method. The N-terminal e...
Source: European Journal of Pharmaceutical Sciences - July 26, 2019 Category: Drugs & Pharmacology Authors: Babazada H, Alekberli T, Hajieva P, Farajov E Tags: Eur J Pharm Sci Source Type: research

Optimization of a paediatric fixed dose combination mini-tablet and dosing regimen for the first line treatment of tuberculosis.
Abstract We aim to optimize the paediatric dosing regimen of isoniazid, rifampicin and pyrazinamide for the first-line treatment of tuberculosis, based on a fixed dose combination (FDC) mini-tablet using simulations. An optimization problem was set up to determine the 3 strengths of the drugs of the mini-tablet and 4 cutoff points that define the weight bands of a dosing chart, simultaneously. Using Monte Carlo simulations, first, exposure targets were determined for the 3 drugs, from published population pharmacokinetic models for adults, assuming that the approved doses for adults are de facto efficacious. Then ...
Source: European Journal of Pharmaceutical Sciences - July 26, 2019 Category: Drugs & Pharmacology Authors: Tsiligiannis A, Sfouni M, Nalda-Molina R, Dokoumetzidis A Tags: Eur J Pharm Sci Source Type: research

Corrigendum to "Role of alum in improving the immunogenicity of biodegradable polymer particle entrapped antigens" [Eur. J. Pharm. Sci., 38, (2009), 18-28].
Corrigendum to "Role of alum in improving the immunogenicity of biodegradable polymer particle entrapped antigens" [Eur. J. Pharm. Sci., 38, (2009), 18-28]. Eur J Pharm Sci. 2019 Jul 26;:105014 Authors: Kanchan V, Katare YK, Panda AK PMID: 31358316 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - July 26, 2019 Category: Drugs & Pharmacology Authors: Kanchan V, Katare YK, Panda AK Tags: Eur J Pharm Sci Source Type: research

Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability.
uacute;nior CSN, Guimarães L, Dos Santos FV, de Castro WV, Viana GHR, de Brito CFA, de Pilla Varotti F Abstract The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compo...
Source: European Journal of Pharmaceutical Sciences - July 22, 2019 Category: Drugs & Pharmacology Authors: Guimarães DSM, de Sousa Luz LS, do Nascimento SB, Silva LR, de Miranda Martins NR, de Almeida HG, de Souza Reis V, Maluf SEC, Budu A, Marinho JA, Abramo C, Carmona AK, da Silva MG, da Silva GR, Kemmer VM, Butera AP, Ribeiro-Viana RM, Gazarini ML, Júnior Tags: Eur J Pharm Sci Source Type: research

Target-mediated disposition population pharmacokinetics model of erythropoietin in premature neonates following multiple intravenous and subcutaneous dosing regimens.
Abstract Routine erythropoietin (Epo) therapy for neonatal anemia is presently controversial due to its modest response. We speculate that an important contributor to this modest response is that previous clinical study designs were not driven by rigorous mechanistic and kinetic insights into the complex pharmacokinetics (PK) and pharmacodynamics (PD) of Epo in this population. To address this therapeutic opportunity, we conducted a prospective clinical study to investigate the PK of Epo in very-low-birth-weight (VLBW) premature neonates using a unique Epo dosing algorithm that accounts for complex neonatal erythr...
Source: European Journal of Pharmaceutical Sciences - July 21, 2019 Category: Drugs & Pharmacology Authors: D'Cunha R, Schmidt R, Widness JA, Mock DM, Yan X, Cress GA, Kuruvilla D, Veng-Pedersen P, An G Tags: Eur J Pharm Sci Source Type: research

Sulfocoumarins, specific carbonic anhydrase IX and XII inhibitors, interact with cancer multidrug resistant phenotype through pH regulation and reverse P-glycoprotein mediated resistance.
In this study, the activity of three new sulfocoumarins was evaluated in three sensitive and corresponding multidrug resistant cancer cell lines with increased P-glycoprotein expression (non-small cell lung carcinoma, colorectal carcinoma and glioblastoma). Compound 3 showed the highest potential for cancer cell growth inhibition in all tested cell lines. Flow cytometric analyses showed that compound 3 induced intracellular acidification, cell cycle arrest in G2/M phase and necrosis in non-small cell lung carcinoma cells. Compound 3 demonstrated irreversible, concentration- and time-dependent inhibition of P-glycoprotein a...
Source: European Journal of Pharmaceutical Sciences - July 19, 2019 Category: Drugs & Pharmacology Authors: Podolski-Renić A, Dinić J, Stanković T, Jovanović M, Ramović A, Pustenko A, Žalubovskis R, Pešić M Tags: Eur J Pharm Sci Source Type: research

Multicomponent self nano emulsifying delivery systems of resveratrol with enhanced pharmacokinetics profile.
nto B Abstract Resveratrol is a drug with high potential for clinical application based on experimental models. Though, resveratrol translation to clinical use has not been successful yet due to its poor pharmacokinetics, related to poor solubility and fast metabolism. The use of drug delivery systems, namely self-emulsifying drug delivery systems (SEDDS), may be a viable strategy to overcome the poor in vivo performance of resveratrol. In this work, a rational development of two different ternary SEDDS was conducted. Experimental data showed that quantitative variations on SEDDS composition impacted dispersion an...
Source: European Journal of Pharmaceutical Sciences - July 19, 2019 Category: Drugs & Pharmacology Authors: Vasconcelos T, Araújo F, Lopes C, Loureiro A, das Neves J, Marques S, Sarmento B Tags: Eur J Pharm Sci Source Type: research

Synthesis and anti-cancer activity of ND-646 and its derivatives as acetyl-CoA carboxylase 1 inhibitors.
In this study, through public database analysis and clinic sample test, we for the first time verified that ACC1 mRNA is overexpressed in non-small-cell lung cancer (NSCLC), which is accompanied by reduced DNA methylation at CpG island S shore of ACC1. Our study further demonstrated that higher ACC1 levels are associated with poor prognosis in NSCLC patients. Besides, we developed a novel synthetic route for preparation of a known ACC inhibitor ND-646, synthesized a series of its derivatives and evaluated their activity against the enzyme ACC1 and the A549 cell. As results, most of the tested compounds showed potent ACC1 i...
Source: European Journal of Pharmaceutical Sciences - July 17, 2019 Category: Drugs & Pharmacology Authors: Li EQ, Zhao W, Zhang C, Qin LZ, Liu SJ, Feng ZQ, Wen X, Chen CP Tags: Eur J Pharm Sci Source Type: research

Investigation of the permeation enhancer strategy on benzoylaconitine transdermal patch: The relationship between transdermal enhancement strength and physicochemical properties of permeation enhancer.
Abstract Permeation enhancer strategy is used to develop Benzoylaconitine (BA) of high molecular weight (603.7 Da) into transdermal patch. The present study was to achieve a patch with good analgesic and anti-inflammatory effects and investigate the relationship between physicochemical parameters of enhancers and enhancement strength. In vitro skin permeation study was used to evaluate the effect of enhancers, and correlation study was conducted to clarify the relationship between physicochemical parameters of enhancer and permeation amount. The enhancement molecular mechanism was characterized using FT-IR and m...
Source: European Journal of Pharmaceutical Sciences - July 12, 2019 Category: Drugs & Pharmacology Authors: Liu C, Farah N, Weng W, Jiao B, Shen M, Fang L Tags: Eur J Pharm Sci Source Type: research

Preparation of a nanoscale dihydromyricetin-phospholipid complex to improve the bioavailability: in vitro and in vivo evaluations.
In this study, DMY phospholipid complex (DMY-HSPC COM) was prepared by the solvent evaporation technique and optimized with DMY combination ratio. Scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were carried to characterize the formation of DMY-HSPC COM. The particle size, zeta potential, drug loading and solubility of DMY-HSPC COM were further investigated. The phospholipid complex technology could significantly improve the solubility of DMY. Pharmacokinetic study results of DMY-HSPC COM in healthy SD rat...
Source: European Journal of Pharmaceutical Sciences - July 11, 2019 Category: Drugs & Pharmacology Authors: Zhao X, Shi C, Zhou X, Lin T, Gong Y, Yin M, Fan L, Wang W, Fang J Tags: Eur J Pharm Sci Source Type: research

Phenylethyl resorcinol smartLipids for skin brightening - Increased loading & chemical stability.
In this study PER was incorporated into smartLipids, the 3rd generation of lipid carriers. Compared to NLC, the smartLipids formulation had a higher PER loading, was PEG-free and used ECOCERT-certified Lanette N. For PER stabilization, 14 additives from three groups were investigated: UV blockers, antioxidants and chelating agents. The UV blockers Tinosorb S and Oxynex ST liquid, as well as the chelating agents ethylenediaminetetraacetic acid and phytic acid completely prevented reddish discoloration under test conditions (3 months in the dark and 7 days at light exposure). Investigating the stabilizing mechanisms, UV ...
Source: European Journal of Pharmaceutical Sciences - July 11, 2019 Category: Drugs & Pharmacology Authors: Köpke D, Müller RH, Pyo SM Tags: Eur J Pharm Sci Source Type: research

Targeting inhaled fibers to the pulmonary acinus: Opportunities for augmented delivery from in silico simulations.
Abstract Non-spherical particles, and fibers in particular, are potentially attractive airborne carriers for pulmonary drug delivery. Not only do they exhibit a high surface-to-volume ratio relative to spherical aerosols, but their aerodynamic properties also enable them to reach deep into the lungs. Until present, however, our understanding of the deposition characteristics of inhaled aerosols in the distal acinar lung regions has been mostly limited to spheres. To shed light on the fate of elongated aerosols in the pulmonary depths, we explore through in silico numerical simulations the deposition and dispersion...
Source: European Journal of Pharmaceutical Sciences - July 11, 2019 Category: Drugs & Pharmacology Authors: Shachar-Berman L, Ostrovski Y, Koshiyama K, Wada S, Kassinos SC, Sznitman J Tags: Eur J Pharm Sci Source Type: research

Pemetrexed-conjugated hyaluronan for the treatment of malignant pleural mesothelioma.
Abstract Pemetrexed (PMX) is a multi-targeted antifolate drug used for the treatment of malignant pleural mesothelioma (MPM) and non-small cell lung cancer. Hyaluronan (HA) in blood is well known as a disease marker of MPM. We synthesized PMX-conjugated hyaluronan (HA-ADH-PMX) for the first time to develop a novel anticancer chemotherapeutic agent. HAs with different molecular weights (76 and 130 kDa) were first derivatized with adipic dihydrazide (ADH) and then conjugated to PMX. The obtained HA-ADH-PMX retained inhibitory activity against folate metabolism enzymes; thymidylate synthase was inhibited to the sam...
Source: European Journal of Pharmaceutical Sciences - July 11, 2019 Category: Drugs & Pharmacology Authors: Amano Y, Ohta S, Sakura KL, Ito T Tags: Eur J Pharm Sci Source Type: research

In situ antibody-loaded hydrogel for intravitreal delivery.
Abstract Therapeutic protein medicines have transformed the treatment of blinding diseases (e.g. age-related macular degeneration, AMD) during the last 1-2 decades. Many blinding conditions such as AMD are chronic; and require multiple intravitreal injections over a long period to achieve a high and reproducible dose needed for clinical benefit. Prolonging the duration of action of ophthalmic drugs is critical to reduce the frequency of injections. Thermoresponsive hydrogels (e.g. N-isopropylacrylamide, NIPAAM) that collapse in physiological conditions can entrap and sustain the release of a therapeutic protein. H...
Source: European Journal of Pharmaceutical Sciences - July 11, 2019 Category: Drugs & Pharmacology Authors: Awwad S, Abubakre A, Angkawinitwong U, Khaw PT, Brocchini S Tags: Eur J Pharm Sci Source Type: research

A novel core-shell nanofiber drug delivery system intended for the synergistic treatment of melanoma.
In conclusion, the results introduced in this work can be a promising strategy for cancer treatment and possesses synergism potential to broaden an avenue for chemotherapeutic therapy with minimum adverse effects on normal cells. PMID: 31302215 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - July 11, 2019 Category: Drugs & Pharmacology Authors: Zhu LF, Zheng Y, Fan J, Yao Y, Ahmad Z, Chang MW Tags: Eur J Pharm Sci Source Type: research

Pore change during degradation of octreotide acetate-loaded PLGA microspheres: The effect of polymer blends.
This study used PLGA 5050 4H (F-1), PLGA 5050 1A: PLGA 5050 4H = 3:7 (F-2) and PLGA 7525 1A: PLGA 5050 4H = 3:7 (F-3) as a carrier, respectively. Microspheres (MS) were obtained by O/W emulsion solvent evaporation technique and characterized by scanning electron microscopy (SEM), particle size, drug loading, fluorescence characteristics, and in vitro and in vivo release. Accelerated tests in vitro showed that the size and number of core pores significantly affected drug release in the first and second phases. After intramuscular administration, F-2 and F-3 showed effective blood concentration levels and their bioav...
Source: European Journal of Pharmaceutical Sciences - July 11, 2019 Category: Drugs & Pharmacology Authors: Wang T, Xue P, Wang A, Yin M, Han J, Tang S, Liang R Tags: Eur J Pharm Sci Source Type: research

A higher throughput and physiologically relevant two-compartmental human ex vivo intestinal tissue system for studying gastrointestinal processes.
In conclusion, we show that human ex vivo intestinal tissue mounted in the higher throughput InTESTine 6- 24-transwell plate system is easy to handle and a suitable system to study diverse functional GI processes. PMID: 31301485 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - July 10, 2019 Category: Drugs & Pharmacology Authors: Stevens LJ, van Lipzig MMH, Erpelinck SLA, Pronk A, van Gorp J, Wortelboer HM, van de Steeg E Tags: Eur J Pharm Sci Source Type: research

Biphasic drug release testing coupled with diffusing wave spectroscopy for mechanistic understanding of solid dispersion performance.
Abstract Amorphous Solid dispersions (ASDs) represent an important formulation technique to achieve supersaturation in gastrointestinal fluids and to enhance absorption of poorly water-soluble drugs. Drug release from such systems is complex due to emergence of different colloidal structures and potential drug precipitation, which can occur in parallel to absorption. The latter drug uptake from the intestinal lumen can be simulated by an organic layer in a biphasic in vitro test, which was employed in this work to mechanistically study the release of ketoconazole from ASDs produced by hot melt extrusion using diff...
Source: European Journal of Pharmaceutical Sciences - July 10, 2019 Category: Drugs & Pharmacology Authors: Jankovic S, O'Dwyer PJ, Box KJ, Imanidis G, Reppas C, Kuentz M Tags: Eur J Pharm Sci Source Type: research

Empirical investigation of preparations produced according to the European Pharmacopoeia monograph 1038.
Abstract According to the European Pharmacopoeia monograph 1038 (Praeparationes homoeopathicae), homeopathic preparations are produced by successive dilution and succussion steps. Dilution levels beyond Avogadro's limit, however, render specific effects implausible according to standard scientific knowledge. Accordingly, we were interested in a critical empirical investigation of preparations produced according to this monograph. Within a precursor study we developed a bioassay based on a fingerprint metabolomic analysis of Lepidium sativum seeds germinated in vitro in either homeopathic preparations or controls i...
Source: European Journal of Pharmaceutical Sciences - July 8, 2019 Category: Drugs & Pharmacology Authors: Doesburg P, Andersen JO, Scherr C, Baumgartner S Tags: Eur J Pharm Sci Source Type: research

Continuous, simultaneous cocrystallization and formulation of Theophylline and 4-Aminobenzoic acid pharmaceutical cocrystals using twin screw melt granulation.
Abstract In this work a cocrystal of Theophylline and 4Aminobenzoic acid was successfully produced and formulated using a hydrophilic binder with a novel continuous melt granulation approach. This melt granulation was followed with direct compression to generate oral solid dosage forms. The study revealed that the processing temperature, molecular weight of the binder and binder concentration were the most effective parameters for the production and formulation of high purity cocrystals. Superior tableting performance was observed for melt granulated cocrystals as compared with extruded cocrystals and pure theophy...
Source: European Journal of Pharmaceutical Sciences - July 8, 2019 Category: Drugs & Pharmacology Authors: Shaikh R, Walker GM, Croker DM Tags: Eur J Pharm Sci Source Type: research

Piperine-loaded nanoparticles with enhanced dissolution and oral bioavailability for epilepsy control.
Abstract Piperine, an alkaloid from black pepper, has demonstrated beneficial effects in central nervous system, especially in epilepsy control. However, its therapeutic application remains limited due to the low aqueous solubility of piperine. Thus, the present study aimed to formulate piperine into a more solubilized form to enhance its oral bioavailability and facilitate its development as a potential anti-epileptic treatment. The nanoprecipitation method was applied to prepare piperine nanoparticles, which were then examined under transmission electron microscopy. A spherical nanosized particle was obtained wi...
Source: European Journal of Pharmaceutical Sciences - July 7, 2019 Category: Drugs & Pharmacology Authors: Ren T, Hu M, Cheng Y, Shek TL, Xiao M, Ho NJ, Zhang C, Leung SSY, Zuo Z Tags: Eur J Pharm Sci Source Type: research

In vitro activity, ultrastructural studies and in silico pharmacokinetic properties of indol-3-yl-thiosemicarbazones derivatives and analogues against juvenile and adult worms of S. mansoni.
ima M Abstract The present work aimed to carry out in vitro biological assays of indol-3-yl derivatives thiosemicarbazones (2a-e) and 4-thiazolidinones (3a-d) against juvenile and adult worms of S. mansoni, as well as the in silico determination of pharmacokinetic parameters for the prediction of the oral bioavailability of these derivatives. All compounds were initially screened at a concentration of 200 μM against S. mansoni adult worms and the results evidenced the good activity of compounds 2b, 2d and 3b, which caused 100% mortality after 24, 48 and 72 h, respectively. Subsequent studies with these same...
Source: European Journal of Pharmaceutical Sciences - July 5, 2019 Category: Drugs & Pharmacology Authors: de Almeida Júnior ASA, de Oliveira JF, da Silva AL, da Rocha RET, Junior NCP, Gouveia ALA, da Silva RMF, de Azevedo Albuquerque MCP, Brayner FA, Alves LC, do Carmo Alves de Lima M Tags: Eur J Pharm Sci Source Type: research

Thiosemicarbazone derivatives: Design, synthesis and in vitro antimalarial activity studies.
Abstract Different types of thiosemicarbazone derivatives were designed and tested for their Drug-Like Molecular (DLM) nature by using Lipinski and Veber rules. Subsequently, compounds with DLM properties were synthesized and characterized by spectral methods. In vitro antimalarial activity studies of the synthesized thiosemicarbazone derivatives have been carried out against Plasmodium falciparum, 3D7 strain using fluorescence assay method and found that the compounds, (E)-2-(1-(4-fluorophenyl)ethylidene)hydrazine-1-carbothioamide (6), (E)-2-(1-(3-bromophenyl) ethylidene) hydrazine-1-carbothioamide (15) and (E)-2...
Source: European Journal of Pharmaceutical Sciences - July 5, 2019 Category: Drugs & Pharmacology Authors: Matsa R, Makam P, Kaushik M, Hoti SL, Kannan T Tags: Eur J Pharm Sci Source Type: research

Simulated space radiation: Investigating ionizing radiation effects on the stability of amlodipine besylate API and tablets.
Abstract Efficacious pharmaceuticals with the adequate shelf life are essential for the well-being of the space explorers and successful completion of a space mission. Space is brimming with different types of radiations, which penetrate inside the spacecraft despite the shielding material. Such radiations can alter the stability of the pharmaceuticals during long duration space missions. The literature reporting the space radiation effects on the pharmaceuticals is scarce in a public domain. Ground-based simulation studies can be useful to predict the influence of the space radiations on the stability of the phar...
Source: European Journal of Pharmaceutical Sciences - July 2, 2019 Category: Drugs & Pharmacology Authors: Bhayani D, Naik H, Nathaniel TN, Khan S, Mehta P Tags: Eur J Pharm Sci Source Type: research

Zinc pyrithione induces immobilization of human spermatozoa and suppresses the response of the cAMP/PKA signaling pathway.
This study investigated the molecular mechanisms underlying ZPT-induced spermatozoa immobilization by examining plasma membrane integrity, mitochondrial dysfunction, and the cAMP/PKA signaling pathway response. ZPT inhibited spermatozoa motility and movement patterns in a concentration-dependent manner. The 100% effective concentration (EC100) and median effective concentration (EC50) at which ZPT-induced spermatozoa immobilization at 20 s were 40 μmol/L and 16.19 μmol/L, respectively. ZPT did not significantly disrupt spermatozoa plasma membranes, but it exerted a strong and significant effect on the depolariz...
Source: European Journal of Pharmaceutical Sciences - July 2, 2019 Category: Drugs & Pharmacology Authors: Yang M, Hu J, Xia M, Wang Y, Tian F, Li W, Sun Y, Zhou Z Tags: Eur J Pharm Sci Source Type: research

Insights on role of polymers in precipitation of celecoxib from supersaturated solutions as assessed by focused beam reflectance measurement (FBRM).
This study was able to demonstrate the applicability of microarray plate method for quantitative estimations of precipitation kinetics that can be utilized for excipient screening for poorly soluble drugs having intra-luminal precipitation as a problem. FBRM analysis is highly valuable to gain mechanistic insights and put to rest the prevalent conjecture-based role attribution for polymers. PMID: 31271876 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - July 1, 2019 Category: Drugs & Pharmacology Authors: Sodhi I, Mallepogu P, Thorat VP, Kashyap MC, Sangamwar AT Tags: Eur J Pharm Sci Source Type: research

Fabrication and finite element analysis of stereolithographic 3D printed microneedles for transdermal delivery of model dyes across human skin in vitro.
Abstract This research aimed to manufacture and evaluate in vitro 3D printed microneedles for transdermal drug delivery. Firstly, microneedle arrays were fabricated using a polymer-based material. Subsequently, these arrays were tested for their mechanical strength applying axial load along their length, while prediction of the buckling load was performed using widely known arithmetic models. Additionally, the force required to pierce human skin was calculated in order to verify that microneedles insert human skin without buckling or fracturing. Finite Element Analysis (FEA) was used to simulate the insertion proc...
Source: European Journal of Pharmaceutical Sciences - June 26, 2019 Category: Drugs & Pharmacology Authors: Xenikakis I, Tzimtzimis M, Tsongas K, Andreadis D, Demiri E, Tzetzis D, Fatouros DG Tags: Eur J Pharm Sci Source Type: research

Hartmut Derendorfs work on tissue distribution.
PMID: 31254643 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - June 26, 2019 Category: Drugs & Pharmacology Authors: Vozmediano V, Schmidt S Tags: Eur J Pharm Sci Source Type: research

Culture independent approach reveals domination of human-oriented microbes in a pharmaceutical manufacturing facility.
Abstract Strict microbial control is required in pharmaceutical manufacturing facilities, for which environmental microbial monitoring is fundamental. Appropriate microbial control is based on understanding the abundance and community structure of the microbes in the target environment, but most microbes are not culturable by conventional methods. Here, we determined the bacterial abundance and assessed the environmental microbiome in a pharmaceutical manufacturing facility using rRNA gene-targeted quantitative PCR (qPCR) and high-throughput sequencing of rRNA gene fragments. A commercially available microbial par...
Source: European Journal of Pharmaceutical Sciences - June 26, 2019 Category: Drugs & Pharmacology Authors: Kawai M, Ichijo T, Takahashi Y, Noguchi M, Katayama H, Cho O, Sugita T, Nasu M Tags: Eur J Pharm Sci Source Type: research

Modulating the site-specific oral delivery of sorafenib using sugar-grafted nanoparticles for hepatocellular carcinoma treatment.
In this study, solid lipid nanoparticles (SLN) were prepared and appended with polyethylene glycol (PEGylated) galactose and a multikinase inhibitor sorafenib (SRFB) was used as chemotherapeutic drug, for treating hepatocellular carcinoma (HCC). The nanoparticles were evaluated for in-vitro and in-vivo performances to showcase the targeting efficiency and therapeutic benefits of the sorafenib loaded ligand conjugated nanoparticles (GAL-SSLN). When compared with SRFB or Sorafenib loaded SLN, GAL-SSLN showed superior cytotoxicity and apoptosis in HepG2 (human hepatocellular carcinoma cells). In addition, in-vivo pharmacokine...
Source: European Journal of Pharmaceutical Sciences - June 26, 2019 Category: Drugs & Pharmacology Authors: Tunki L, Kulhari H, Vadithe LN, Kuncha M, Bhargava S, Pooja D, Sistla R Tags: Eur J Pharm Sci Source Type: research

Colloidal (-)-epigallocatechin-3-gallate vesicular systems for prevention and treatment of skin cancer: A comprehensive experimental study with preclinical investigation.
Abstract Skin carcinogenesis is a common malignancy affecting humans worldwide, which could benefit from nutraceuticals as a solution to the drawbacks of conventional skin cancer treatment. (-)-epigallocatechin-3-gallate (EGCG) is a promising nutraceutical in this regard; however, it suffers chemical instability and low bioavailability resulting in inefficient delivery. Therefore, EGCG encapsulation in ultradeformable colloidal vesicular systems, namely: penetration enhancer-containing vesicles (PEVs), ethosomes and transethosomes (TEs) for topical administration has been attempted in this study to overcome the pr...
Source: European Journal of Pharmaceutical Sciences - June 25, 2019 Category: Drugs & Pharmacology Authors: El-Kayal M, Nasr M, Elkheshen S, Mortada N Tags: Eur J Pharm Sci Source Type: research