Exploring the Enzymatic Degradation of Poly(Glycerol Adipate).
Abstract Poly(glycerol adipate) (PGA) is a biodegradable, biocompatible, polymer with a great deal of potential in the field of drug delivery. Active drug molecules can be conjugated to the polymer backbone or encapsulated in self-assembled nanoparticles for targeted and systemic delivery. Here, a range of techniques have been used to characterise the enzymatic degradation of PGA extensively for the first time and to provide an indication of the way the polymer will behave and release drug payloads in vivo. Dynamic Light Scattering was used to monitor change in nanoparticle size, indicative of degradation. The rel...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 15, 2019 Category: Drugs & Pharmacology Authors: Swainson SME, Taresco V, Pearce AK, Clapp LH, Ager B, McAllister M, Bosquillon C, Garnett MC Tags: Eur J Pharm Biopharm Source Type: research

Intestinal absorption-modifying excipients: a current update on preclinical in vivo evaluations.
uml;s H Abstract Pharmaceutical excipients in drug products are defined as pharmacologically inactive and are integral constituents of all types of oral dosage forms. However, some excipients may increase drug absorption by interacting with the mucosal membrane. If the strategy is to use an excipient with a potential to affect the processes determining the rate and/or extent of the intestinal drug absorption, it is defined as an absorption-modifying excipients (AME). These pharmaceutical excipients may act as AMEs, depending on the amounts applied, and accordingly influence bioequivalence assessment of innovative ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 12, 2019 Category: Drugs & Pharmacology Authors: Dahlgren D, Sjöblom M, Lennernäs H Tags: Eur J Pharm Biopharm Source Type: research

Bridging in vitro dissolution and in vivo exposure for acalabrutinib. Part II. A mechanistic PBPK model for IR formulation comparison, proton pump inhibitor drug interactions, and administration with acidic juices.
Abstract Acalabrutinib (Calquence®) 100 mg (bid) has received accelerated approval by FDA for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Acalabrutinib is a substrate of PgP and CYP3A4, with a significant fraction of drug metabolized by first pass gut extraction and 25% absolute bioavailability. The absorption of acalabrutinib is affected by stomach pH, with lower pharmacokinetic exposure observed following co-administration with proton pump inhibitors. During dissolution at pH values below its highest basic pKa, the two basic moieties of acalab...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 12, 2019 Category: Drugs & Pharmacology Authors: Pepin XJH, Moir AJ, Mann JC, Sanderson NJ, Barker R, Meehan E, Plumb AP, Bailey GR, Murphy DS, Krejsa CM, Andrew MA, Ingallinera TG, Greg Slatter J Tags: Eur J Pharm Biopharm Source Type: research

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate.
sti M Abstract The stability of live-attenuated viruses is very challenging due to thermal sensitivity; therefore, solid form is usually required (often freeze-dried products). Micropellet technology is a lyophilization technology that has the potential to provide greater flexibility in the presentation of a given vaccine particularly in multi-dose format or in combination of different vaccines. As a novel vaccine alternative process, this spray freeze-dried (SFD) micropellet technology was evaluated using as a model a yellow fever virus produced in Vero cells (vYF). Screening of excipients was performed in order ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 12, 2019 Category: Drugs & Pharmacology Authors: Clénet D, Hourquet V, Woinet B, Ponceblanc H, Vangelisti M Tags: Eur J Pharm Biopharm Source Type: research

Effects of absorption-modifying excipients on jejunal drug absorption in simulated fasted and fed luminal conditions.
rnäs H Abstract Oral administration of drug products is the preferred administration route. In recent decades there has been an increase in drug candidates with low solubility and/or low permeability. To increase the possibility of oral administration for the poorly permeating drugs, the use of absorption modifying excipients (AMEs) has been proposed. These types of AMEs may also affect the regulatory assessment of a novel drug delivery system if they affect the absorption of a drug from any of the four BCS classes. The effects of AMEs have previously been investigated in various animal models, including the ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 12, 2019 Category: Drugs & Pharmacology Authors: Roos C, Dahlgren D, Sjögren E, Sjöblom M, Hedeland M, Lennernäs H Tags: Eur J Pharm Biopharm Source Type: research

Bridging in vitro dissolution and in vivo exposure for acalabrutinib. Part I. Mechanistic modelling of drug product dissolution to derive a P-PSD for PBPK model input.
Abstract Drug product dissolution for four batches of acalabrutinib 100 mg capsules were analyzed with in vitro dissolution in various pH conditions and in media containing synthetic surfactant micelles or biorelevant micelles. Non-sink conditions, where the drug is unionized, were used to derive a batch specific drug product particle size distribution (P-PSD). The purpose of this P-PSD is to serve as an input in physiological based pharmacokinetic (PBPK) models to calculate in vivo dissolution in various administration conditions. The P-PSD was used to predict dissolution in all other conditions tested, introduci...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 12, 2019 Category: Drugs & Pharmacology Authors: Pepin XJH, Sanderson NJ, Blanazs A, Grover S, Ingallinera TG, Mann JC Tags: Eur J Pharm Biopharm Source Type: research

In vivo evaluation of solid lipid microparticles and hybrid polymer-lipid microparticles for sustained delivery of leuprolide.
In conclusion, spray-dried PLGA-triglyceride hybrid MPs can be used as better carriers than other MPs for subcutaneous delivery of peptide drugs due to the synergetic effect of lipids and PLGA for sustained drug release from the spray-dried MP. PMID: 31299277 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 9, 2019 Category: Drugs & Pharmacology Authors: Wu C, Luo X, Baldursdottir SG, Yang M, Sun X, Mu H Tags: Eur J Pharm Biopharm Source Type: research

Thermosensitive hybrid hydrogels for the controlled release of bioactive vancomycin in the treatment of orthopaedic implant infections.
Abstract The purpose of this work was the development of antibacterial delivery systems for vancomycin, with potential application in the prevention of orthopedic implant infections. Previous studies have shown tandem thermal gelling and Michael addition cross-linking of hydrogels based on (meth)acrylated triblock copolymers of PEG-p(HPMAm-lac1-2) and thiolated hyalutronic acid. In this work we extended this technology synthesizing new vinyl sulfone derivatives of PEG-p(HPMAm-lac1-2) triblock copolymers and used them in combination with thiolated hyaluronic acid as controlled delivery systems for vancomycin. It wa...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 8, 2019 Category: Drugs & Pharmacology Authors: Censi R, Casadidio C, Dubbini A, Cortese M, Scuri S, Grappasonni I, Golob S, Vojnovic D, Giovanna Sabbieti M, Agas D, Di Martino P Tags: Eur J Pharm Biopharm Source Type: research

Scale-Up of pharmaceutical Hot-Melt-Extrusion: Process optimization and transfer.
In conclusion, the ratio of the applied energy for transport to mixing is identified as valuable addition in this context. PMID: 31295504 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 8, 2019 Category: Drugs & Pharmacology Authors: Wesholowski J, Hoppe K, Nickel K, Muehlenfeld C, Thommes M Tags: Eur J Pharm Biopharm Source Type: research

Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats.
z A Abstract The influence of physiological factors on the solubility of drug compounds has been thoroughly investigated in humans. However, as these factors vary between species and since many in vivo studies are carried out in rats or mice, it has been difficult to establish sufficient in vitro in vivo relations. The aim of this study was to develop a physiologically relevant in vitro dissolution model simulating the gastrointestinal (GI) fluids of fasted rats and compare it to previously published in vitro and in vivo data. To develop the in vitro model, the pH was measured in situ in six segments of the GI tra...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 6, 2019 Category: Drugs & Pharmacology Authors: Fjelrad Christfort J, Strindberg S, Plum J, Hall-Andersen J, Janfelt C, Hagner Nielsen L, Müllertz A Tags: Eur J Pharm Biopharm Source Type: research

Preparation of maltodextrin nanoparticles and encapsulation of bovine serum albumin - influence of formulation parameters.
er M Abstract Maltodextrin, which is obtained by partial hydrolysis of starch, is water soluble and could serve as hydrophilic carrier for the encapsulation of protein based active pharmaceutical ingredients. We investigated three different commercial maltodextrins (Dextrose Equivalents (DE) 4.0 - 7.0, DE 13.0 - 17.0, and DE 16.5 - 19.5) with focus on their ability to form nanoparticles by inverse precipitation. Successful particle formation was observed for DE 13.0 - 17.0, and DE 16.5 - 19.5 but not for DE 4.0 - 7.0. The process was investigated using acetone as anti-solvent and poloxamer 407 as stabilizer. A tun...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 6, 2019 Category: Drugs & Pharmacology Authors: Barthold S, Hittinger M, Primavessy D, Zapp A, Groß H, Schneider M Tags: Eur J Pharm Biopharm Source Type: research

Rat intestinal drug permeability: a status report and summary of repeated determinations.
This report showed that the SPIP and ICL methods are important in situ models for understanding and predicting intestinal drug absorption. However, conclusions based on permeability values sourced from different laboratories may not be reliable. Because each permeability study is unique and because between- and even within-laboratory variability can be substantial, data from individual studies should preferably be interpreted separately. PMID: 31283980 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 5, 2019 Category: Drugs & Pharmacology Authors: Dubbelboer I, Dahlgren D, Sjögren E, Lennernäs H Tags: Eur J Pharm Biopharm Source Type: research

The crucial role of macromolecular engineering, drug encapsulation and dilution on the thermoresponsiveness of UCST diblock copolymer nanoparticles used for hyperthermia.
s N Abstract Poly(acrylamide-co-acrylonitrile) (P(AAm-co-AN)), an upper critical solution temperature (UCST)-type copolymer in water, was synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization and used as a macro-RAFT agent for the polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) to yield amphiphilic diblock P(AAm-co-AN)-b-POEGMA copolymer. A series of copolymers with different AN content was obtained allowing to finely tune the UCST behavior (cloud point (Tt-UCST) from 35 to 78°C). Addition of the POEGMA block did not modify the Tt-UCST regardless its...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 4, 2019 Category: Drugs & Pharmacology Authors: Bordat A, Soliman N, Ben Chraït I, Manerlax K, Yagoubi N, Boissenot T, Nicolas J, Tsapis N Tags: Eur J Pharm Biopharm Source Type: research

A unified in vitro test system for the assessment of tight junction modulators.
In this study, eight well-known TJ modulators were tested with a focus on four different in vitro bioassays carried out with MDCK cells. The extent of TJ modulation was determined by transepithelial electric resistance (TEER) measurements and permeability studies with mannitol. To evaluate tolerability, cell viability (MTT) and cytotoxicity (CellToxTM Green) assays were performed, and TEER regeneration was monitored for 24 h after exposure. With the exception of labradimil, seven TJ modulators caused significant TEER reduction of up to 100 %. For five compounds, an enhancement of mannitol permeation was observed. As expect...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 3, 2019 Category: Drugs & Pharmacology Authors: Saaber D, Reichl S Tags: Eur J Pharm Biopharm Source Type: research

Fenofibrate oral absorption from SNEDDS and super-SNEDDS is not significantly affected by lipase inhibition in rats.
Müllertz A Abstract The effect of drug load and digestion on the solubilization and absorption of fenofibrate in self-nanoemulsifying drug delivery system (SNEDDS) was assessed in a pharmacokinetic study in rats and in an in vitro lipolysis model. SNEDDS containing fenofibrate at 75 % of equilibrium solubility (Seq), a super-saturated SNEDDS (super-SNEDDS) containing fenofibrate at 150 % of Seq and a super-SNEDDS suspension containing fenofibrate at 100 % of Seq and an additional 50 % Seq fenofibrate suspended (150 % of Seq in total) were used. To assess the effect of lipid digestion on fenofibrate absorption...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 2, 2019 Category: Drugs & Pharmacology Authors: Høtoft Michaelsen M, Siqueira Jørgensen SD, Mahad Abdi I, Wasan KM, Rades T, Müllertz A Tags: Eur J Pharm Biopharm Source Type: research

How to Measure Coating Thickness of Tablets: Method Comparison of Optical Coherence Tomography, Near-infrared Spectroscopy and Weight-, Height- and Diameter Gain.
We present a method comparison between in-line (optical coherence tomography and near-infrared spectroscopy) and well-established off-line (height-, weight- and diameter-gain) approaches to determining the coating thickness of tablets. We used single tablets drawn during a commercial coating process. Comparing the low intra- and high inter-tablet coating variability indicated that the tablets had a broad distribution of spray zone passes but at a random tablet orientation. Even at the end of the coating process at a mean coating thickness of about 70µm, the inter-tablet standard deviation was about 9µm or 13% r...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 1, 2019 Category: Drugs & Pharmacology Authors: Wahl PR, Peter A, Wolfgang M, Khinast JG Tags: Eur J Pharm Biopharm Source Type: research

AbstractActivity and pharmacokinetics of a praziquantel crystalline polymorph in the Schistosoma mansoni mouse model.
Abstract Schistosomiasis is a global disease of significant public health relevance. Only one racemic drug, praziquantel, characterized by low bioavailability low water solubility and extensive first pass metabolism, is currently available. We studied a new praziquantel formulation (polymorph B), which is based on a racemic praziquantel crystalline polymorph (TELCEU01). It's in vitro activity was tested on newly transformed schistosomula (NTS) and adult Schistosoma mansoni In vivo studies were conducted in mice harboring chronic S. mansoni infections. Pharmacokinetic PK profiles of R- and S-praziquantel and R- S- ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 29, 2019 Category: Drugs & Pharmacology Authors: Lombardo FC, Perissutti B, Keiser J Tags: Eur J Pharm Biopharm Source Type: research

Platelet lysate loaded electrospun scaffolds: effect of nanofiber types on wound healing.
Abstract In healthy individuals, wound healing is a highly efficient process. However, interruptions of normal healing give rise to chronic wounds, characterized by inflammation with impaired angiogenesis and re-epithelialization. The aim of the present work was the design and the development of electrospun nanofibrous scaffolds based on sodium alginate (SA) and pullulan (PUL) and loaded with human platelet lysate (PL) intended for skin reparation, to take the advantage of nanofibrous scaffolds (with improved physical structure) and of SA as biopolymer. Two preparation approaches have been used to load PL in the s...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 29, 2019 Category: Drugs & Pharmacology Authors: Malgarim Cordenonsi L, Faccendini A, Rossi S, Cristina Bonferoni M, Malavasi L, Raffin R, Eva Scherman Schapoval E, Del Fante C, Vigani B, Miele D, Sandri G, Ferrari F Tags: Eur J Pharm Biopharm Source Type: research

Achieving Continuous Manufacturing in Lyophilization: Technologies and Approaches.
Abstract This paper provides an organic overview of the most interesting continuous freeze-drying concepts that have been proposed over the years. Attention has mainly been focused on the field of pharmaceuticals, but some background has also been given on the food industry. This work aims at providing a solid starting point for future research on continuous manufacturing for the freeze-drying of pharmaceuticals. PMID: 31252071 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 25, 2019 Category: Drugs & Pharmacology Authors: Pisano R, Arsiccio A, Capozzi LC, Trout BL Tags: Eur J Pharm Biopharm Source Type: research

Determination of drug-polymer solubility from supersaturated spray-dried amorphous solid dispersions: a case study with Efavirenz and Soluplus ®.
Determination of drug-polymer solubility from supersaturated spray-dried amorphous solid dispersions: a case study with Efavirenz and Soluplus®. Eur J Pharm Biopharm. 2019 Jun 24;: Authors: Costa BLA, Sauceau M, Del Confetto S, Sescousse R, Ré MI Abstract Amorphous solid dispersions (ASDs) are found to be a well-established strategy for overcoming limited aqueous solubility and poor oral bioavailability of active pharmaceutical ingredients (APIs). One of the main parameters affecting ASDs physical stability is the API solubility in the carrier, because this value determines the maximal API ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 24, 2019 Category: Drugs & Pharmacology Authors: Costa BLA, Sauceau M, Del Confetto S, Sescousse R, Ré MI Tags: Eur J Pharm Biopharm Source Type: research

Nanomedicine for the effective and safe delivery of non-steroidal anti-inflammatory drugs: a review of preclinical research.
Abstract The toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) is one of the major limitations to their long-term use in the treatment of chronic inflammatory conditions. This review provides an overview of the preclinical efforts on the development of nanodelivery systems for NSAIDs with a focus on the effect of nanoformulation on the pharmacokinetics and pharmacodynamics of the delivered drugs. Preclinical and clinical studies have shown that nanomedicine products can reduce toxicity and enhance the efficacy of encapsulated certain therapeutics. In this context, significant effort has been devoted to the...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 21, 2019 Category: Drugs & Pharmacology Authors: Al-Lawati H, Binkhathlan Z, Lavasanifar A Tags: Eur J Pharm Biopharm Source Type: research

In vivo Models and Decision Trees for Formulation Development in Early Drug Development: A Review of Current Practices and Recommendations for Biopharmaceutical Development.
This article offers a perspective on the use of in vivo models and biopharmaceutical decision trees in the development of new oral drug products. PMID: 31233862 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 21, 2019 Category: Drugs & Pharmacology Authors: Zane P, Gieschen H, Kersten E, Mathias N, Ollier C, Johansson P, Van den Bergh A, Van Hemelryck S, Reichel A, Rotgeri A, Schäfer K, Müllertz A, Langguth P Tags: Eur J Pharm Biopharm Source Type: research

Measuring the Specific Surface Area (SSA) of Freeze-Dried Biologics using Inverse Gas Chromatography.
Abstract The specific surface area (SSA) of freeze-dried biologics (FD) is usually measured via a Brunauer-Emmett-Teller (BET) analysis of volumetric nitrogen/krypton adsorption isotherms. However, this technique has accuracy limitations for materials
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 21, 2019 Category: Drugs & Pharmacology Authors: Duralliu A, Matejtschuk P, Williams DR Tags: Eur J Pharm Biopharm Source Type: research

Surface Activity Profiling (SAP): A potential means of predicting intestinal membrane permeability.
n J Abstract Early characterization of new drug substances intended for oral application includes not only physicochemical properties and stability but also the ability of the substance to permeate through the intestinal mucosa. In this work, a rapid screening method, surface activity profiling (SAP), is proposed as an alternative to animal studies and screening in cell cultures. Measurements are made with a multichannel tensiometer and require only 50 microliters of stock solution for the complete permeability analysis. Correlation of SAP results with human absorption was demonstrated for marketed drugs and with ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 20, 2019 Category: Drugs & Pharmacology Authors: Rosenberger J, Schmid K, Schäfer KJ, Dressman J Tags: Eur J Pharm Biopharm Source Type: research

Self-assembled amphiphilic copolymers as dual delivery system for immunotherapy.
Abstract Subunit vaccines using recombinant antigens appear as the privileged vaccination technology for safety reasons but still require the development of carriers/adjuvants ensuring optimal immunogenicity and efficacy. Micelles from self-assembled amphiphilic copolymers have recently emerged as highly relevant and promising candidates owing to their ease of preparation, low size (entering in lymphatic capillaries for reaching lymph nodes), size/surface tunability and chemical versatility enabling introduction of stimuli (e.g. pH) responsive features and biofunctionalization with dedicated molecules. In particul...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 20, 2019 Category: Drugs & Pharmacology Authors: Trimaille T, Lacroix C, Verrier B Tags: Eur J Pharm Biopharm Source Type: research

Light sheet fluorescent microscopy versus confocal microscopy: in quest of a suitable tool to assess drug and nanomedicine penetration into multicellular tumor spheroids.
In this study, we used these hetero-type spheroids as a tool to assess the penetration of doxorubicin (used as a model drug) through the whole tumor mass either in a free form or loaded into polymer nanoparticles, and we investigated whether microscopy images, acquired by Confocal Laser Scanning Microscopy (CLSM) and Light Sheet Fluorescence Microscopy (LSFM), would be best to provide reliable information on this process. Results clearly demonstrated that CLSM was not suitable to accurately monitor the diffusion of small molecules such as the doxorubicin. Indeed, it only allowed to scan a layer of 100 µm depth and no...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 19, 2019 Category: Drugs & Pharmacology Authors: Lazzari G, Vinciguerra D, Balasso A, Nicolas V, Goudin N, Garfa-Traore M, Féher A, Dinnyés A, Nicolas J, Couvreur P, Mura S Tags: Eur J Pharm Biopharm Source Type: research

The sub-chronic impact of mPEG2k-PCLx polymeric nanocarriers on cytochrome P450 enzymes after intravenous administration in rats.
Abstract Recent studies indicated obvious impacts of nano-carriers on cytochrome P450 enzymes (CYP450s) in vitro, but the effects in vivo are still unknown. In the present research, mPEG2k-PCLx micelles with different length of hydrophobic block (2000∼10000 Da) were intravenously administrated into rats for 14 days to evaluate the sub-chronic influences in the metabolic function of hepatic CYP450s. Although CYP1A1/B2 was susceptible to mPEG2k-PCLx micelles compared with other CYP isoenzymes, induction was mainly observed and varied with micelle type, administration dose, and CYP isoform. Interestingly, mPEG2k-...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 18, 2019 Category: Drugs & Pharmacology Authors: Li Q, Sun M, Li G, Qiu L, Huang Z, Gong J, Huang J, Li G, Si L Tags: Eur J Pharm Biopharm Source Type: research

Stability behaviour of antiretroviral drugs and their combinations. 10: LC-HRMS, LC-MSn, LC-NMR and NMR characterization of fosamprenavir degradation products and in silico determination of their ADMET properties.
Abstract The present study focused upon the forced degradation behaviour of fosamprenavir (FPV), an antiretroviral drug. A total of six degradation products (DPs) were separated on a non-polar stationary phase by high performance liquid chromatography (HPLC). For the characterization, comprehensive mass fragmentation pathway of the drug was initially established using high resolution mass spectrometry (HRMS) and multi-stage tandem mass spectrometry (MSn) data. Subsequently, LC-HRMS and LC-MSn studies were carried out on the forced degraded samples containing the DPs. Five DPs were isolated and subjected to extensi...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 18, 2019 Category: Drugs & Pharmacology Authors: Kumar Singh D, Sahu A, Abdullah Wani A, Bharatam PV, Narayana Kotimoole C, Balaji Batkulwar K, Yashwantrao Deshpande A, Giri S, Singh S Tags: Eur J Pharm Biopharm Source Type: research

Mathematical modeling of the heterogeneous distributions of nanomedicines in solid tumors.
The objective for this study is to develop a mathematical model to quantitatively analyze this phenomenon and the influencing factors to such perivascular distribution and seek for effective strategies to alleviate this. A spatial tumor distribution model was firstly constructed to mimic the geometrical structure of tumor vessels and the surrounding tumor cells. This tumor model was further integrated with a systemic pharmacokinetics model for nanoparticles. A variety of factors on the tumor spatial distributions of nanomedicines were considered in the model. With the model, we quantified the effect of these influencing fa...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 18, 2019 Category: Drugs & Pharmacology Authors: He H, Liu C, Liu Y, Liu X, Wu Y, Fan J, Zhao L, Cao Y Tags: Eur J Pharm Biopharm Source Type: research

Pitfalls in Analyzing Release from Chitosan/Tripolyphosphate Micro- and Nanoparticles.
Abstract Submicron particles prepared by complexing chitosan with tripolyphosphate (TPP) attract widespread interest as potential drug, gene and vaccine delivery vehicles, and many published studies examine their release properties. Despite these sustained efforts, however, literature on the release performance of chitosan/TPP micro- and nanoparticles is filled with conflicting results, with some reporting nearly instantaneous release, while others showing the release to be sustained for up to multiple days. To resolve these opposing findings, we recently postulated that the in vitro release profiles obtained from...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 18, 2019 Category: Drugs & Pharmacology Authors: Cai Y, Lapitsky Y Tags: Eur J Pharm Biopharm Source Type: research

Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles.
Abstract Despite many years of research and a few success stories with gene therapeutics, efficient and safe DNA delivery remains a major bottleneck for the clinical translation of gene-based therapies. Gene transfection with calcium phosphate (CaP) nanoparticles brings the advantages of low toxicity, high DNA entrapment efficiency and good endosomal escape properties. The macroscale aggregation of CaP nanoparticles can be easily prevented through surface coating with bisphosphonate conjugates. Bisphosphonates, such as alendronate, recently showed promising anticancer effects. However, their poor cellular permeabi...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 17, 2019 Category: Drugs & Pharmacology Authors: Bisso S, Mura S, Castagner B, Couvreur P, Leroux JC Tags: Eur J Pharm Biopharm Source Type: research

Rational manufacturing of functionalized, long-term stable perfluorocarbon-nanoemulsions for site-specific 19F magnetic resonance imaging.
CONCLUSION: The established PFC-NE platform offers a cost-efficient way to produce larger amounts of long-term storable imaging agents, which can be surface-modified on demand for application in targeted 19FMRI. PMID: 31220572 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 17, 2019 Category: Drugs & Pharmacology Authors: Krämer W, Grapentin C, Bouvain P, Temme S, Flögel U, Schubert R Tags: Eur J Pharm Biopharm Source Type: research

Saliva: an all-rounder of our body.
Abstract Saliva is a multifaceted bodily fluid that is often taken for granted but is indispensable for oral health and overall well-being in humans. Although mainly comprised of water (99.5%), proteins, ions and enzymes turn saliva into a viscoelastic solution that performs a variety of vital tasks. This review article gives a brief overview of the salivary gland system, as well as the composition, output and functions of saliva. It also addresses the current applications of saliva for diagnostic purposes, the clinical relevance of saliva in oral diseases as well as current treatment options. PMID: 31220573 ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 17, 2019 Category: Drugs & Pharmacology Authors: Roblegg E, Coughran A, Sirjani D Tags: Eur J Pharm Biopharm Source Type: research

Development of a sprayable hydrogel formulation for the skin application of therapeutic antibodies.
inter G Abstract A formulation of an antibody with antibacterial properties for topical use on Staphylococcal skin infections was developed and characterized. The best formulation was obtained with 1.5% (w/v) sodium carboxymethylcellulose containing 10mg/ml immunoglobulin. Spraying forces and rheological behavior were measured in order to characterize the hydrogel formulation. The percentage of antibody aggregates in gel as well as the antibody release, folding and target binding properties of the released antibody were analyzed to proof an acceptable shelf life and no significant changes in the activity of the an...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 14, 2019 Category: Drugs & Pharmacology Authors: Geh KJ, Stelzl A, Gröne A, Wagner L, Förster B, Winter G Tags: Eur J Pharm Biopharm Source Type: research

A Non-Covalent Antibody Complex for the Delivery of anti-cancer drugs.
Abstract Antibody drug conjugates (ADCs), which are obtained by coupling a potent cytotoxic agent to a monoclonal antibody (mAb), are traditionally bound in a random way to lysine or cysteine residues, with the final product's heterogeneity having an important impact on their activity, characterization, and manufacturing. A new antibody drug delivery system (ADS) based on a non-covalent linkage between a Fc-binding protein, in this case Protein A or Protein G, and a mAb was investigated in the effort to achieve greater homogeneity and to create a versatile and adaptable drug delivery system. Recombinant staphyloco...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 12, 2019 Category: Drugs & Pharmacology Authors: Maso K, Monia Montagner I, Grigoletto A, Schiavon O, Rosato A, Pasut G Tags: Eur J Pharm Biopharm Source Type: research

Evaluation of drug permeability calculation based on luminal disappearance and plasma appearance in the rat single-pass intestinal perfusion model.
rnäs H Abstract The rat single-pass intestinal perfusion (SPIP) model is commonly used to investigate gastrointestinal physiology and membrane drug transport. The SPIP model can be used with the intestinal segment inside or outside the abdomen. The rats can also be treated with parecoxib, a selective cycloxygenase-2 inhibitor that has been shown to affect some intestinal functions following abdominal surgery, such as motility, epithelial permeability, fluid flux and ion transport. However, the impact of extra-abdominal placement of the intestinal segment in combination with parecoxib on intestinal drug transp...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 12, 2019 Category: Drugs & Pharmacology Authors: Dahlgren D, Roos C, Peters K, Lundqvist A, Tannergren C, Sjögren E, Sjöblom M, Lennernäs H Tags: Eur J Pharm Biopharm Source Type: research

Lipidoid-Polymer Hybrid Nanoparticles Loaded with TNF siRNA Suppress Inflammation after Intra-articular Administration in a Murine Experimental Arthritis Model.
eng X Abstract Rheumatoid arthritis (RA) is a common autoimmune disease, which is characterized by painful chronic inflammation in the joints, and novel safe and efficacious treatments are urgently needed. RNA interference (RNAi) therapy based on small interfering RNA (siRNA) is a promising approach for silencing specific genes involved in inflammation. However, delivery of siRNA to the target site, i.e. the cytosol of immune cells, is a challenge. Here, we designed lipid-polymer hybrid nanoparticles (LPNs) composed of lipidoid and poly(DL-lactic-co-glycolic acid) loaded with a therapeutic cargo siRNA directed aga...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 11, 2019 Category: Drugs & Pharmacology Authors: Jansen MAA, Klausen LH, Thanki K, Lyngsø J, Skov Pedersen J, Franzyk H, Nielsen HM, van Eden W, Dong M, Broere F, Foged C, Zeng X Tags: Eur J Pharm Biopharm Source Type: research

Do interactions between Protein and Phospholipids influence the release behavior from lipid-based exenatide depot systems?
In conclusion, erosion of the VPG matrix and membrane permeability of the drug are the major parameters influencing the release of exenatide from VPGs of POPC-POPG, whereas drug binding to the membranes had a minor effect only. PMID: 31195130 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 10, 2019 Category: Drugs & Pharmacology Authors: Breitsamer M, Stulz A, Heerklotz HH, Winter G Tags: Eur J Pharm Biopharm Source Type: research

Simulated, biorelevant, clinically relevant or physiologically relevant dissolution media: The hidden role of bicarbonate buffer.
g R Abstract In-vitro dissolution testing of pharmaceutical formulations has been used as a quality control test for many years. At early drug product development, in vivo predictive dissolution testing can be used for guidance in the rational selection of candidate formulations that best fit the desired in vivo dissolution characteristics. At present, the most widely applied dissolution media are phosphate-based buffers and, in some cases, the result of dissolution tests performed in such media have demonstrated reasonable/acceptable IVIVCs. However, the presence of phosphates in human GI luminal fluids is insign...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 10, 2019 Category: Drugs & Pharmacology Authors: Amaral Silva D, Al-Gousous J, Davies NM, Bou Chacra N, Webster GK, Lipka E, Amidon G, Löbenberg R Tags: Eur J Pharm Biopharm Source Type: research

Topical semifluorinated alkane based azithromycin suspension for the management of ocular infections.
ID Abstract The management of ocular infections is challenging due to poor drug bioavailability and vehicle related adverse effects associated with current antibiotic eye drops. Semifluorinated alkanes (SFAs) are reportedly well-tolerated on the ocular surface and can enhance ocular drug bioavailability. Therefore, an SFA-based azithromycin suspension (SFA-AZM) was prepared and its antibacterial efficacy was compared that that of marketed azithromycin eye drops by monitoring the growth of bioluminescent Staphylococcus aureus in ex vivo ocular tissues. Corneal and conjunctival distribution of hydrophobic fluoresce...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 10, 2019 Category: Drugs & Pharmacology Authors: Agarwal P, Craig JP, Krösser S, Eickhoff K, Swift S, Rupenthal ID Tags: Eur J Pharm Biopharm Source Type: research

Protein-Functionalized Nanoparticles Derived from End-Functional Polymers and Polymer Prodrugs for Crossing the Blood-Brain Barrier.
Abstract Nanoparticles may provide a viable way for neuroprotective drugs to cross the blood-brain barrier (BBB), which limits the passage of most drugs from the peripheral circulation to the brain. Heterotelechelic polymer prodrugs comprising a neuroprotective model drug (adenosine) and a maleimide functionality were synthesized by the "drug-initiated" approach and subsequent nitroxide exchange reaction. Nanoparticles were obtained by nanoprecipitation and exhibited high colloidal stability with diameters in the 162-185 nm range and narrow size distributions. Nanoparticles were then covalently surface-c...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 6, 2019 Category: Drugs & Pharmacology Authors: Cox A, Vinciguerra D, Re F, Dal Magro R, Mura S, Masserini M, Couvreur P, Nicolas J Tags: Eur J Pharm Biopharm Source Type: research

Imine bond formation: A novel concept to incorporate peptide drugs in self-emulsifying drug delivery systems (SEDDS).
CONCLUSION: According to these findings, the concept of imine bond formation with cinnamaldehyde can be considered as a novel concept for increasing lipophilicity of the hydrophilic antibiotic peptide PMB. PMID: 31176724 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 6, 2019 Category: Drugs & Pharmacology Authors: Dizdarević A, Ari Efiana N, Nhu Quynh Phan T, Matuszczak B, Bernkop Schnürch A Tags: Eur J Pharm Biopharm Source Type: research

Tumor microenvironment determines drug efficacy in vitro - apoptotic and anti-inflammatory effects of 15-lipoxygenase metabolite, 13-HpOTrE.
In conclusion, 13-HpOTrE reduces viability of skin cancer cells in 2D cultures only but modulates inflammatory cytokine levels in the corresponding 3D tumor constructs, too. These studies highlight the need for screening of anticancer drugs employing 3D tumors and including tumor microenvironment in the screening process to increase the low success rate of clinical trials in oncology. PMID: 31176725 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 6, 2019 Category: Drugs & Pharmacology Authors: Wolff C, Zoschke C, Kumar Kalangi S, Reddanna P, Schäfer-Korting M Tags: Eur J Pharm Biopharm Source Type: research

Novel Non-linear Curve Fitting to Resolve Protein Unfolding Transitions in Intrinsic Fluorescence Differential Scanning Fluorimetry.
ing; Abstract In biotherapeutic protein research, an estimation of the studied protein's thermal stability is one of the important steps that determine developability as a function of solvent conditions. Differential Scanning Fluorimetry (DSF) can be applied to measure thermal stability. Label-free DSF measures amino acid fluorescence as a function of temperature, where conformational changes induce observable peak deformation, yielding apparent melting temperatures. The estimation of the stability parameters can be hindered in the case of multidomain, multimeric or aggregating proteins when multiple transitions p...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 5, 2019 Category: Drugs & Pharmacology Authors: Augustijn D, Mahapatra S, Streicher W, Svilenov H, Kulakova A, Pohl C, Rinnan Å Tags: Eur J Pharm Biopharm Source Type: research

Corrigendum to "In vitro combinatorial anticancer effects of 5-fluorouracil and curcumin loaded N,O-carboxymethyl chitosan nanoparticles toward colon cancer and in vivo pharmacokinetic studies" [Eur. J. Pharmaceut. Biopharmaceut. 88 (2014) 238-251].
Corrigendum to "In vitro combinatorial anticancer effects of 5-fluorouracil and curcumin loaded N,O-carboxymethyl chitosan nanoparticles toward colon cancer and in vivo pharmacokinetic studies" [Eur. J. Pharmaceut. Biopharmaceut. 88 (2014) 238-251]. Eur J Pharm Biopharm. 2019 Jun;139:44-46 Authors: Anitha A, Sreeranganathan M, Chennazhi KP, Lakshmanan VK, Jayakumar R PMID: 31054763 [PubMed - in process] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 7, 2019 Category: Drugs & Pharmacology Authors: Anitha A, Sreeranganathan M, Chennazhi KP, Lakshmanan VK, Jayakumar R Tags: Eur J Pharm Biopharm Source Type: research

Nanoshells Prepared by Atomic Layer Deposition - Long Acting Depots of Indomethacin.
In conclusion, this is the first long-term in vivo evaluation of nanoshell depot formulations. The stable plasma concentrations for more than 12 weeks demonstrate that nanoshells can enable long-term depot injections with high drug load. PMID: 31055064 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 2, 2019 Category: Drugs & Pharmacology Authors: Hellrup J, Rooth M, Mårtensson E, Sigfridsson K, Johansson A Tags: Eur J Pharm Biopharm Source Type: research

Evaluation of collagen/hydroxyapatite electrospun layers loaded with vancomycin, gentamicin and their combination: Comparison of release kinetics, antimicrobial activity and cytocompatibility.
In conclusion, COL/HA layers with 15 wt% of HA impregnated with vancomycin or with a combination of vancomycin and gentamicin offer a promising treatment approach and the potential to prevent infection during the joint replacement procedures. PMID: 31055065 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 2, 2019 Category: Drugs & Pharmacology Authors: Suchý T, Šupová M, Sauerová P, Hubálek Kalbáčová M, Klapková E, Pokorný M, Horný L, Závora J, Ballay R, Denk F, Sojka M, Vištejnová L Tags: Eur J Pharm Biopharm Source Type: research

Comparison of two different PEGylation strategies for the liposomal adjuvant CAF09: Towards induction of CTL responses upon subcutaneous vaccine administration.
In conclusion, PEGylation of CAF09 may be a useful strategy for the design of an adjuvant, which induces CTL responses after s.c. and i.m. administration. In the present studies, CAF09 grafted with 10 mol% DSPE-PEG2000 is the most promising of the tested adjuvants, but additional studies are required to further elucidate the potential of the strategy. PMID: 31055066 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 2, 2019 Category: Drugs & Pharmacology Authors: Tandrup Schmidt S, Line Olsen C, Franzyk H, Wørzner K, Smith Korsholm K, Rades T, Andersen P, Foged C, Christensen D Tags: Eur J Pharm Biopharm Source Type: research

Preface.
PMID: 31005249 [PubMed - in process] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 22, 2019 Category: Drugs & Pharmacology Authors: Agrahari V, J Rathbone M Tags: Eur J Pharm Biopharm Source Type: research

Effect of Implantation Site on Outcome of Tissue-Engineered Vascular Grafts.
CONCLUSION: Our PCL grafts in the carotid position were well endothelialised with early cellular infiltration, higher compliance, lower IH and calcification compared to the similar grafts implanted in the aortic position. However, there was a higher occlusion rate compared to our abdominal aorta series. Anatomical position, compliance mismatch, flow conditions may answer the difference in patency seen. PMID: 31004790 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 17, 2019 Category: Drugs & Pharmacology Authors: Sologashvili T, Saat SA, Tille JC, De Valence S, Mugnai D, Pierre Giliberto J, Dillon J, Yakub A, Dimon Z, Gurny R, Walpoth BH, Moeller M Tags: Eur J Pharm Biopharm Source Type: research