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Eur J Pharm Biopharm 2019 Feb 16. Epub 2019 Feb 16.

School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. Electronic address:

Small interfering RNA (siRNA) has recently illustrated therapeutic potential for malignant disorders. However, the clinical application of siRNA-based therapeutics is significantly retarded by the paucity of successful delivery systems. Recently, multifunctional gold nanoparticles (AuNPs) as non-viral delivery carriers have shown promise for transporting chemotherapeutics, proteins/peptides, and genes. Read More

Eur J Pharm Biopharm 2019 Feb 16. Epub 2019 Feb 16.

School of Pharmacy, Jiangsu University, 301# Xuefu Road, Zhenjiang, Jiangsu, China. Electronic address:

Targeted delivery of bioactive compounds such as proteins to the colon has numerous advantages for the therapeutic treatment of inflammatory bowel disease. The present study sought to fabricate alginate/chitosan microcapsules containing IL-1Ra (Alg/Chi/IL-1Ra MC) via a single-step electrospraying method. Two important factors of efficacy were measured-the pH-responsiveness of the microcapsule and the in-vitro drug release profile. Read More

Eur J Pharm Biopharm 2019 Feb 16. Epub 2019 Feb 16.

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address:

The use of nanomaterials is increasing but the real risk associated with their use in humans has to be defined. In fact, nanomaterials tend to accumulate in organs over a long period of time and are slowly degraded or eliminated by the body. Exosomes are nanovesicles actively shuttle molecules, including chemical products and metals, through the body. Read More

Eur J Pharm Biopharm 2019 Feb 15. Epub 2019 Feb 15.

Department of Biochemistry, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address:

Elastin-like polypeptide (ELP) nanoparticles are a versatile platform for targeted drug delivery. As for any type of nanocarrier system an important challenge remains the ability of deep (tumor) tissue penetration. In this study, ELP particles with controlled surface density of the cell-penetrating peptide (CPP) octa-arginine (R8) were created by temperature-induced co-assembly. Read More

Eur J Pharm Biopharm 2019 Feb 15. Epub 2019 Feb 15.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address:

The tumor microenvironment is the cellular environment that is also described as the "soil" for supporting tumor growth, proliferation, invasion and metastasis, as well as protecting tumor cells from immunological recognition. Notably, tumor cells can grow much faster than other normal organs and invade surrounding tissues more easily, which results in abnormal expression of enzymes in the tumor microenvironment, including matrix metalloproteinases (MMPs), cathepsins, phospholipases, oxidoreductases, etc. In opposite, due to the high selectivity and catalytic activity, these enzymes can promote nanoparticles to recognize tumor tissues more accurately, which enhances therapeutic efficacy with lower systemic toxicity. Read More

Eur J Pharm Biopharm 2019 Feb 14. Epub 2019 Feb 14.

University of Pavia, Department of Drug Sciences, 27100 Pavia, Italy; Pharmaexceed srl, 27100 Pavia, Italy.

This paper aims at demonstrating silk fibroin nanoparticles (SFNs) promote anti-inflammatory properties of celecoxib (CXB) or curcumin (CUR), and could be exploited for osteoarthritis (OA) treatment. Nanoparticles were prepared by desolvation method and physico-chemically characterized (FT-IR, DSC, TGA, SEM, size distribution and drug release); empty and drug loaded nanoparticles were tested for their ROS-scavenging activity, hemolytic properties, cytotoxicity, and anti-inflammatory potency in an OA in vitro model. Results indicate that a controlled drug release has been achieved by varying the drug loading. Read More

Eur J Pharm Biopharm 2019 Feb 13. Epub 2019 Feb 13.

Division of Advanced Materials and Healthcare Technologies, School of Pharmacy, The University of Nottingham, NG7 2RD, UK. Electronic address:

Basal cell carcinoma (BCC) is the most common skin cancer in humans. Topical treatment with imiquimod provides a non-invasive, self-administered treatment with relatively low treatment cost. Despite displaying excellent efficacy, imiquimod is only licensed by the FDA for superficial BCC. Read More

Eur J Pharm Biopharm 2019 Feb 13. Epub 2019 Feb 13.

Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden; Swedish Drug Delivery Forum (SDDF), Uppsala University, Sweden. Electronic address:

In this review we will discuss how computational methods, and in particular classical molecular dynamics simulations, can be used to calculate solubility of pharmaceutically relevant molecules and systems. To the extent possible, we focus on the non-technical details of these calculations, and try to show also the added value of a more thorough and detailed understanding of the solubilization process obtained by using computational simulations. Although the main focus is on classical molecular dynamics simulations, we also provide the reader with some insights into other computational techniques, such as the COSMO-method, and also discuss Flory-Huggins theory and solubility parameters. Read More

Eur J Pharm Biopharm 2019 Feb 12. Epub 2019 Feb 12.

Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Sri-Ayutthaya Road, Rajathavee, Bangkok, Thailand; Center of Excellence in Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. Electronic address:

The purpose of this study was to evaluate the effect of charge on the in vitro drug performances of clarithromycin nanocrystals. To prepare different charges of nanocrystals, media milling was employed with the use of different stabilizing systems. The uncharged nanocrystals were prepared from poloxamer 407. Read More

Eur J Pharm Biopharm 2019 Feb 7. Epub 2019 Feb 7.

Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan,. Electronic address:

Aim: Intracerebroventricular (ICV) administration of ultrasound-responsive bubbles and cranial ultrasound irradiation is reported as a transfection system for the cerebroventricular region. This study aimed to characterize the transfection system with respect to transfection efficiency, spatial distribution of transgene expression, and safety.

Methods: Plasmid DNA was transfected to mouse brain by ICV injection of ultrasound-responsive nanobubbles, followed by ultrasound irradiation to brain. Read More

Eur J Pharm Biopharm 2019 Feb 5. Epub 2019 Feb 5.

Department of Pharmacy, University of Greifswald, 17489 Greifswald, Germany. Electronic address:

Accurate prediction of oral absorption of drugs relies on biorelevant methodology. Current methods are based on Western healthy adult populations. Malnourished children have many differences in their gastrointestinal anatomy and physiology compared to a healthy Western adult. Read More

Eur J Pharm Biopharm 2019 Mar 5;136:259-266. Epub 2019 Feb 5.

MyLife Technologies B.V., Leiden Bio Science Park, BioPartner 4, Unit 4358, Robert Boyleweg 4, 2333 CG Leiden, the Netherlands; Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, 2300 RA Leiden, the Netherlands. Electronic address:

Microneedle arrays (MNAs) are a promising mean to administer vaccines. Without the need of highly trained personnel, MNAs can be applied to deliver vaccines into the dermis, which is well equipped to initiate potent immune responses. While vaccination using dissolving microneedle arrays has been extensively investigated, the use of solid nanoporous MNAs (npMNAs) to deliver vaccines remained largely unexplored. Read More

Eur J Pharm Biopharm 2019 Mar 28;136:221-230. Epub 2019 Jan 28.

Department of Biopharmaceutics and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Felix-Hausdorff-Straße 3, 17489 Greifswald, Germany. Electronic address:

In preclinical research, Beagle dogs are an important model for formulation development and for evaluation of food effects on drug absorption. In this study, the gastrointestinal transit conditions in Beagle dogs were studied with a telemetric motility capsule at different intake conditions. In a cross-over study design, the SmartPill® was given to six Beagle dogs to measure transit times, pH values, pressures and temperatures in the different parts of the canine GI tract. Read More

Eur J Pharm Biopharm 2019 Mar 28;136:231-239. Epub 2019 Jan 28.

Institute of Physics, University of Silesia, ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland; Silesian Center for Education and Interdisciplinary Research, ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.

In this paper we determined the solubility limits of the amorphous flutamide within the two different polymeric matrixes - poly vinylpyrrolidone and poly vinylacetate. In order to achieve this goal, series of broadband dielectric spectroscopy measurements were performed. As a result we found that the maximal amount of the drug that can be successfully dissolved within the PVAc (maintaining the non-supersaturated conditions) is equal to 35 wt% of the amorphous solid dispersion system. Read More

Eur J Pharm Biopharm 2019 Mar 28;136:213-220. Epub 2019 Jan 28.

Department of Chemical and Biological Engineering, Center for Pharmaceutical Biotechnology, University of Colorado, Boulder, CO 80309, United States. Electronic address:

No United States Food and Drug Administration-licensed vaccines protective against Ebola virus (EBOV) infections are currently available. EBOV vaccine candidates currently in development, as well as most currently licensed vaccines in general, require transport and storage under a continuous cold chain in order to prevent potential decreases in product efficacy. Cold chain requirements are particularly difficult to maintain in developing countries. Read More

Eur J Pharm Biopharm 2019 Mar 25;136:184-191. Epub 2019 Jan 25.

Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Electronic address:

Continuous drug administration with better adherence to treatment and less invasive procedures is important in treating retinal diseases such as age-related macular disease. In this study, we report a drug-refillable device consisting of a silicone reservoir and an injectable gelatin/chitosan gel (iGel). The silicone reservoir was fabricated with polydimethylsiloxane (PDMS) using a computer-aided design and manufacturing to have micropores at a releasing side for uniaxial release to the sclera. Read More

Eur J Pharm Biopharm 2019 Mar 25;136:164-173. Epub 2019 Jan 25.

Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, Oviedo, Spain; Centro Comunitario de Sangre y Tejidos de Asturias, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U714), Oviedo, Spain.

A new in vitro human corneal epithelial model (QobuR) obtained from normal limbal tissue has been developed to study ocular irritancy of different ophthalmic compounded drugs. Phenotypical characterization and trans-epithelial electrical resistance (TEER) of QobuR revealed essential similarities compared with a native human cornea, displaying functional markers and TEER values near 1500 Ωcm at day 7th of cellular differentiation. Using this model, ocular irritancy and barrier integrity alterations were evaluated using MTT reaction and variations in TEER. Read More

Eur J Pharm Biopharm 2019 Mar 24;136:250-258. Epub 2019 Jan 24.

Department of Pharmacy-Drug Science, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy. Electronic address:

This work aims at designing a drug delivery system for rifampicin (RIF) to be used for the therapy of infections from mycobacterium tuberculosis or other lung-colonizing bacteria. We are proposing, in particular, the delivery of RIF by micelles based on inulin functionalized with vitamin E (INVITE). We previously demonstrated that INVITE micelles are formed from the self-assembling sustained by the interaction, within the hydrophobic core, of aromatic groups belonging to vitamin E. Read More

Eur J Pharm Biopharm 2019 Mar 22;136:156-163. Epub 2019 Jan 22.

LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, R. Dr. Roberto Frias, 4200-465 Porto, Portugal. Electronic address:

Temozolomide (TMZ) is the first-line treatment for Glioblastoma Multiforme (GBM). After administration, TMZ is rapidly converted into its active metabolite (MTIC). However, its pharmacological activity is reduced due MTIC low bioavailability in the brain. Read More

Eur J Pharm Biopharm 2019 Mar 22;136:147-155. Epub 2019 Jan 22.

Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany. Electronic address:

Chitosan is object of pharmaceutical research as a candidate permeability enhancer. However, chitosan was recently shown to reduce the oral bioavailability of acyclovir in humans. The effect of chitosan on two processes determining the oral bioavailability of acyclovir, bioaccessibility and intestinal absorption, was now investigated. Read More

Eur J Pharm Biopharm 2019 Mar 21;136:203-212. Epub 2019 Jan 21.

Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany.

Purpose: Conventional chemotherapy is associated with therapy-limiting side effects, which might be alleviated by targeted chemotherapeutics such as immunoliposomes. The targeting ligands of immunoliposomes are commonly attached by unspecific chemical conjugation, bearing risk of structural heterogeneity and therewith related biological consequences. Chemoenzymatic methods may mitigate such risks through site-specific conjugation. Read More

Eur J Pharm Biopharm 2019 Mar 17;136:120-130. Epub 2019 Jan 17.

The Netherlands Cancer Institute, Division of Pharmacology, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address:

Lorlatinib, a novel generation oral anaplastic lymphoma kinase (ALK) and ROS1 inhibitor with high membrane and blood-brain barrier permeability, recently received accelerated approval for treatment of ALK-rearranged non-small-cell lung cancer (NSCLC), and its further clinical development is ongoing. We previously found that the efflux transporter P-glycoprotein (MDR1/ABCB1) restricts lorlatinib brain accumulation and that the drug-metabolizing enzyme cytochrome P450-3A (CYP3A) limits its oral availability. Using genetically modified mouse models, we investigated the impact of targeted pharmacological inhibitors on lorlatinib pharmacokinetics and bioavailability. Read More

Eur J Pharm Biopharm 2019 Mar 17;136:131-137. Epub 2019 Jan 17.

Department of Molecular Pharmaceutics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. Electronic address:

Cocrystallization is an attractive and promising technology that can improve the physical properties of formulations of active pharmaceutical ingredients (APIs). We have developed a "nano-spot method" that can evaluate the crystalline form on the nanogram scale. In this study, the following studies were performed to obtain versatile and comprehensive improvements to the nano-spot method: modification of the sample solution, application of solvent vapor exposure to attempt the precipitation of various states of crystals, and adoption of low-frequency Raman spectroscopy. Read More

Eur J Pharm Biopharm 2019 Mar 22;136:138-146. Epub 2019 Jan 22.

Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey. Electronic address:

An ideal cancer therapy targets the tumor cells selectively without damaging healthy tissues. Even though the tumor-specific markers are limited, these molecules can be used for the delivery of anti-cancer drugs as an active targeting strategy. Since the lymphatic system plays a critical role in the dissemination of cancer cells, the drugs directed through lymphatics can feasibly reach to the sites of metastasis. Read More

Eur J Pharm Biopharm 2019 Mar 17;136:108-119. Epub 2019 Jan 17.

Department of Biotechnology, Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia; Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia. Electronic address:

The interest in probiotics has grown in recent years due to increased awareness of the importance of microbiota for human health. We present the development of monolithic poly(ethylene oxide) and composite poly(ethylene oxide)/lyoprotectant nanofibers loaded with the probiotic Lactobacillus plantarum ATCC 8014. High loading was achieved for L. Read More

Eur J Pharm Biopharm 2019 Mar 17;136:93-101. Epub 2019 Jan 17.

Heinrich Heine University Düsseldorf, Institute of Pharmaceutics and Biopharmaceutics, Universitätsstr. 1, 40225 Düsseldorf, Germany. Electronic address:

Continuously manufactured orodispersible films (ODFs) offer a promising approach for individualized therapy with an easy to administer solid dosage form. The aim of this study was to develop a long ODF containing warfarin sodium to enable safe and more flexible dosing. Formulation development was conducted systematically for the continuous film coating process. Read More

Eur J Pharm Biopharm 2019 Mar 17;136:102-107. Epub 2019 Jan 17.

The University of Queensland, School of Pharmacy, Pharmacy Australia Centre of Excellence, 20 Cornwall Street, Woolloongabba, Brisbane, QLD 4102, Australia. Electronic address:

The intravitreal route faces many challenges in rapidly and effectively reaching posterior eye pathology, with administered therapeutics experiencing non-specific distribution around and premature clearance from ocular tissues. Nanobubbles and ultrasound may improve outcomes of intravitreally administered drugs by influencing the directionality of drug-containing particle migration. In this study, we assessed the impact of trans-scleral or corneal ultrasound application on the distribution of intravitreally-injected nanobubbles. Read More

Eur J Pharm Biopharm 2019 Mar 16;136:192-202. Epub 2019 Jan 16.

Johannes Gutenberg-Universität, Staudingerweg 5, 55099 Mainz, Germany. Electronic address:

Characterization of dissolution of solid suspended drug particles in vivo is important for developing biopredictive in vitro tests. Therefore, methods to gain deeper insights into particle dissolution in vivo are needed. The soft Bioperm intubation method, a well established tool for investigation of permeability, absorption, metabolism, and drug interactions at predefined locations in the gastroinstinal tract, was modified. Read More

Eur J Pharm Biopharm 2019 Mar 17;136:84-92. Epub 2019 Jan 17.

Department of Scienze della Vita e dell'Ambiente, CNBS, University of Cagliari, Cagliari, Italy.

In the present work curcumin loaded hyalurosomes were proposed as innovative systems for the treatment of rheumatoid arthritis. Vesicles were prepared using a one-step and environmentally friendly method. Aiming at finding the most suitable formulation in terms of size, surface charge and stability on storage, an extensive pre-formulation study was performed using different type and amount of phospholipids. Read More

Eur J Pharm Biopharm 2019 Mar 14;136:174-183. Epub 2019 Jan 14.

Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Dpto. de Farmacia y Tecnología Farmacéutica y Parasitología, Vicente Andrés Estelles s/n, Burjassot, Valencia, Spain.

Hydrogels are widely studied as drug delivery system. In this work we propose the employment of tetrakis(hydroxymethyl)phosphonium chloride as crosslinking agent to obtain covalent hydrogels based on chitosan. These hydrogels are obtained by Mannich reaction between the amino groups of chitosan with the hydroxymethyl groups of the crosslinker molecule. Read More

Eur J Pharm Biopharm 2019 Jan 12. Epub 2019 Jan 12.

School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, Geneva, Switzerland. Electronic address:

mPEG-hexPLA micelles have shown their ability to improve delivery and cutaneous bioavailability of a wide range of poorly water soluble and lipophilic molecules. Although poorly water soluble, imiquimod (IMQ) is only moderately lipophilic and it was decided to investigate whether mPEG-hexPLA polymeric micelles could be used as a drug delivery system for this "less than ideal" candidate for encapsulation. Nanosized IMQ micelles (d = 27 nm) were formulated and characterized. Read More

Eur J Pharm Biopharm 2019 Mar 9;136:29-37. Epub 2019 Jan 9.

Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata 573-0101, Japan. Electronic address:

We are investigating an imaging agent for early detection of colorectal cancer. The agent, named the nanobeacon, is coumarin 6-encapsulated polystyrene nanospheres whose surfaces are covered with poly(N-vinylacetamide) and peanut agglutinin that reduces non-specific interactions with the normal mucosa and exhibits high affinity for terminal sugars of the Thomsen-Friedenreich antigen, which is expressed cancer-specifically on the mucosa, respectively. We expect that cancer can be diagnosed by detecting illumination of intracolonically administered nanobeacon on the mucosal surface. Read More

Eur J Pharm Biopharm 2019 Mar 8;136:18-28. Epub 2019 Jan 8.

Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA. Electronic address:

Multidrug resistance (MDR) significantly decreases the therapeutic efficiency of anti-cancer drugs. Its reversal could serve as a potential method to restore the chemotherapeutic efficiency. Downregulation of MDR-related proteins with a small interfering RNA (siRNA) is a promising way to reverse the MDR effect. Read More

Eur J Pharm Biopharm 2019 Mar 8;136:48-69. Epub 2019 Jan 8.

School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, New Zealand. Electronic address:

Transdermal drug delivery offers several attractive advantages over the traditional oral and parenteral routes. Particularly, in case of paediatric patients, it helps to overcome the issues specific to this population, such as difficulty in swallowing and palatability of oral medicines as well as fear and pain associated with needles. However, due to the formidable barrier characteristic of the stratum corneum, it fails in the effective systemic delivery of broad range of therapeutic molecules, especially macromolecules and genetic material. Read More

Eur J Pharm Biopharm 2019 Mar 7;136:240-249. Epub 2019 Jan 7.

Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark; Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016 Shenyang, China. Electronic address:

In this study, we investigated the feasibility of incorporating protein drugs into electrospun fibrous mats (EFMs) for wound healing using lysozyme as a model drug. Lysozyme nanoparticles (Lyso- NPs) were first obtained by electrospray. Lysozyme solutions were prepared with a binary solvent mixture of ethanol (EtOH)-water (HO) at varied volume ratios. Read More

Eur J Pharm Biopharm 2019 Mar 8;136:38-47. Epub 2019 Jan 8.

University of Copenhagen, Department of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address:

The aim of this study was to investigate new porous flexible substrates, i.e., solid foams that would serve as a carrier with a high ink absorption potential for inkjet printable pharmaceuticals. Read More

Eur J Pharm Biopharm 2019 Mar 7;136:9-17. Epub 2019 Jan 7.

Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address:

This paper proposes the development of imiquimod-loaded polymeric nanocapsules formulation for the treatment of cervical cancer. The mechanism of death involved in the reduction of the cell viability as well as the production of an inflammation marker (IL-6) after the treatment in cell line SiHa have been evaluated. The formulation has significantly decreased the viability of the cells in a time-dependent manner, after 24, 48 and 72 h. Read More

Eur J Pharm Biopharm 2019 Mar 4;136:1-8. Epub 2019 Jan 4.

Liverpool John Moores University, School of Pharmacy and Biomolecular Sciences, Liverpool L3 3AF, UK. Electronic address:

RNA interference (RNAi) based therapeutics are considered an endogenous mechanism for modulating gene expression. In addition, microRNAs (miRNAs) may be tractable targets for the treatment of Chronic Obstructive Pulmonary Disease (COPD). In this study miR146a was adsorbed onto poly (glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, nanoparticles (NPs) to reduce target gene IRAK1 expression. Read More

Eur J Pharm Biopharm 2019 Feb 24;135:72-82. Epub 2018 Dec 24.

Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany. Electronic address:

Non-viral vectors are a safe, efficient and non-toxic alternative to viral vectors for gene therapy against many diseases ranging from genetic disorders to cancers. Polyamidoamine (PAMAM), a positively charged dendrimer has a tendency to complex with nucleic acids (to form dendriplexes) like plasmid DNA (pDNA) and small interfering RNA (siRNA) and can shield them from enzymatic degradation, thereby facilitating endocytosis and endosomal release. In this study, we developed an advanced variant of the dendriplexes by encapsulating them within liposomes to enhance their gene delivery efficiency. Read More

Eur J Pharm Biopharm 2019 Feb 21;135:83-93. Epub 2018 Dec 21.

Department of Pharmaceutics, University of Florida, USA.

Fibroblast growth factor peptide (FGF-P) is a polypeptide analog of FGF-2 that could be a potential mitigation and treatment agent for radiation syndromes. Prior to conducting preclinical pharmacokinetics, we developed and validated the LC-MS/MS bioanalytical method for determination of FGF-P in rat plasma for the first time. FGF-P was extracted from rat plasma using the protein precipitation technique followed liquid-liquid extraction using dichloromethane as a solvent. Read More

Eur J Pharm Biopharm 2019 Feb 22;135:49-60. Epub 2018 Dec 22.

Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.

Continuous powder feeding is a critical step in continuous manufacturing of solid dosage forms, as this unit operation should ensure the mass flow consistency at the desired powder feed rate to guarantee the process throughput and final product consistency. In this study, twin-screw feeding of a pharmaceutical formulation (i.e. Read More

Eur J Pharm Biopharm 2019 Feb 21;135:94-103. Epub 2018 Dec 21.

School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, UK. Electronic address:

Hypertension and dyslipidaemia are modifiable risk factors associated with cardiovascular diseases (CVDs) and often require a complex therapeutic regimen. The administration of several medicines is commonly associated with poor levels of adherence among patients, to which World Health Organisation (WHO) proposed a fixed-dose combination unit (polypill) as a strategy to improve adherence. In this work, we demonstrate the fabrication of patient-specific polypills for the treatment of CVDs by fused deposition modelling (FDM) 3D printing and introduce a novel solution to meet critical quality attributes. Read More

Eur J Pharm Biopharm 2019 Mar 20;136:70-83. Epub 2018 Dec 20.

Drug Delivery and Disposition, KU Leuven, Herestraat 49, Gasthuisberg, O&N2, Box 921, 3000 Leuven, Belgium. Electronic address:

The availability of in vitro tools that are constructed on the basis of a detailed knowledge of key aspects of gastrointestinal (GI) physiology and their impact on formulation performance and subsequent drug release behaviour is fundamental to the success and efficiency of oral drug product development. Over the last six years, the development and optimization of improved, biorelevant in vitro tools has been a cornerstone of the IMI OrBiTo (Oral Biopharmaceutics Tools) project. By bringing together key industry and academic partners, and by linking tool development and optimization to human studies to understand behaviour at the formulation/GI tract interface, the collaboration has enabled innovation, optimization and implementation of the requisite biorelevant in vitro tools. Read More

Eur J Pharm Biopharm 2019 Feb 18;135:44-48. Epub 2018 Dec 18.

Department of Micro- and Nanotechnology, Technical University of Denmark, Oersteds Plads 345C, 2800 Kgs. Lyngby, Denmark.

Vaccines provide great benefit for global health, but are insufficiently distributed in developing countries due to high costs of manufacturing and limited storage stability. Spray drying formulations of peptide-based vaccines offer a promising strategy to reduce production costs and improve unrefrigerated storage stability. This design of experiments investigated how adjusting spray drying parameters (inlet temperature, atomization pressure, feed rate and aspiration rate) affects residual moisture and reconstitution properties of the powder product, and morphology and size of the rehydrated particles. Read More

Eur J Pharm Biopharm 2019 Feb 12;135:61-71. Epub 2018 Dec 12.

Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Thrombomodulin (TM) is a type-I transmembrane glycoprotein expressed on the surfaces of endothelial cells and epidermal keratinocytes. It is known to regulate blood coagulation, inflammation, and cell-cell adhesion. A recombinant TM, which contains an epidermal growth factor-like domain and serine/threonine-riches domain, has been demonstrated to stimulate cell proliferation and migration of keratinocytes and wound healing. Read More

Eur J Pharm Biopharm 2019 Feb 11;135:25-35. Epub 2018 Dec 11.

CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, and Department of Chemical Physics, iCHEM, University of Science and Technology of China, Jinzai Road 96, Hefei 230026, Anhui, China. Electronic address:

Efficient delivery of hydrophobic photosensitizer (PS) into tumor cells is a key step for photodynamic therapy (PDT). Redox-responsive polymeric nanoparticles of amphiphilic macro-photosensitizer has designed and prepared as a prodrug-like pro-photosensitizer (pro-PS) for PDT. PEG works as the hydrophilic block and the near infrared (NIR) brominated BODIPY derivative (BDP) works as the hydrophobic PS, and they were linked via the disulfide bond as PEG-SS-BDP, which could be broken for drug release owing to the high GSH concentration inside tumor cells. Read More

Eur J Pharm Biopharm 2019 Feb 10;135:36-43. Epub 2018 Dec 10.

University of Antwerp, Department of Pharmaceutical, Biomedical and Veterinary Sciences, Laboratory of Pharmaceutical Technology and Biopharmacy, Universiteitsplein 1, B-2610 Wilrijk, Belgium. Electronic address:

Tablets are increasingly explored as dosage form for oral probiotics, especially for applications such as pharyngitis and dental health. In such tablets, the dry form increases the stability and the shelf life of the product. In addition, the probiotic cells are entrapped in the tablet matrix, which protects them against the environmental factors in the human body. Read More

Eur J Pharm Biopharm 2019 Jan 4;134:185-189. Epub 2018 Dec 4.

Department of Pharmacy-Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, 81377 Munich, Germany. Electronic address:

In this communication, the effect of mannitol and trehalose crystallization on the unfolding of IgG, a monoclonal antibody, in the frozen state with repeat freeze/thaw under different pH conditions was explored. Formulations were annealed at -20 °C for 20 h five times (interrupted by freeze/thaw). This was done to induce excipient crystallization. Read More

Eur J Pharm Biopharm 2019 Feb 5;135:13-24. Epub 2018 Dec 5.

University of Greifswald, Department of Pharmacy, Institute of Biopharmaceutics and Pharmaceutical Technology, Center of Drug Absorption and Transport (C_DAT), Felix-Hausdorff-Straße 3, 17489 Greifswald, Germany. Electronic address:

The efficacy of narrow therapeutic index (NTI) drugs is closely related to their plasma concentration-time profile. Particularly for these compounds interindividual variability of gastrointestinal (GI) parameters relevant to in vivo drug release may result in fluctuations of the plasma concentration. The present study focused on assessing the influence of individual GI pH- and transit profiles on drug release of enteric valproate tablet formulations by means of individualized in vitro dissolution experiments. Read More

Eur J Pharm Biopharm 2019 Feb 5;135:1-12. Epub 2018 Dec 5.

KU Leuven - University of Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, Leuven B-3000, Belgium. Electronic address:

In spite of the large research efforts in the past two decades, it is still difficult, if possible at all, to predict what manufacturing technology will lead to the best amorphous solid dispersions (ASDs) in terms of drug to polymer ratio ("drug loading") and physical stability. In general, ASDs can be prepared by solvent based methods, heat based methods and mechanochemical activation. In the current study, one manufacturing technique per category was selected: spray drying, hot melt extrusion and cryo-milling, respectively. Read More