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Barbara Cortese, Stefania D'Amone, Ilaria Elena Palamà
Chronic myeloid leukaemia (CML) is caused by the BCR-ABL oncogene, which encodes the constitutively active BCR-ABL tyrosine kinase. Targeted therapy with tyrosine-kinase inhibitors induces a partial cytogenetic response in most patients. Nanosystems can represent an opportunity for combinatorial therapy with the capacity to simultaneously release different therapeutic agents, checking the pharmacokinetic properties. In this work, we have developed a novel poly-(ε-caprolactone) (PCL) nanosystem for combinatorial therapy in CML, composed of a biodegradable pH sensitive core releasing Nilotinib (Nil) and an enzymatic sensitive outer shell releasing Imatinib Mesylate (IM), resulting in wool-like nanoparticles (NPs)...
April 18, 2018: Pharmaceutics
Nivesh K Mittal, Bivash Mandal, Pavan Balabathula, Saini Setua, Dileep R Janagam, Leonard Lothstein, Laura A Thoma, George C Wood
Doxorubicin cardiotoxicity has led to the development of superior chemotherapeutic agents such as AD 198. However, depletion of healthy neutrophils and thrombocytes from AD 198 therapy must be limited. This can be done by the development of a targeted drug delivery system that delivers AD 198 to the malignant cells. The current research highlights the development and in vitro analysis of targeted liposomes containing AD 198. The best lipids were identified and optimized for physicochemical effects on the liposomal system...
April 15, 2018: Pharmaceutics
Jens Wesholowski, Andreas Berghaus, Markus Thommes
In the framework of Quality-by-Design (QbD), the inline determination of process parameters or quality attributes of a product using sufficient process analytical technology (PAT) is a center piece for the establishment of continuous processes as a standard pharmaceutical technology. In this context, Twin-Screw-Extrusion (TSE) processes, such as Hot-Melt-Extrusion (HME), are one key aspect of current research. The main benefit of this process technology is the combination of different unit operations. Several of these sub-processes are linked to the Residence Time Distribution (RTD) of the material within the apparatus...
April 15, 2018: Pharmaceutics
Wejdan Al-Shakarchi, Ali Alsuraifi, Mohammed Abed, Marwan Abdullah, Alan Richardson, Anthony Curtis, Clare Hoskins
Hepatocellular carcinoma is an aggressive form of liver cancer that displays minimal symptoms until its late stages. Unfortunately, patient prognosis still remains poor with only 10% of patients surviving more than five years after diagnosis. Current chemotherapies alone are not offering efficient treatment, hence alternative therapeutic approaches are urgently required. In this work, we highlight the potential of combination of treatment of hepatocellular carcinoma with existing chemotherapies in combination with pro-apoptotic factor cytochrome C...
April 12, 2018: Pharmaceutics
Jaya Mishra, Thomas Rades, Korbinian Löbmann, Holger Grohganz
Ball-milling is usually used to prepare co-amorphous drug-amino acid (AA) mixtures. In this study, co-amorphous drug-AA mixtures were produced using spray-drying, a scalable industrially preferred preparation method. The influence of the solvent type and solvent composition was investigated. Mixtures of indomethacin (IND) and each of the three AAs arginine, histidine, and lysine were ball-milled and spray-dried at a 1:1 molar ratio, respectively. Spray-drying was performed at different solvent ratios in (a) ethanol and water mixtures and (b) acetone and water mixtures...
April 12, 2018: Pharmaceutics
Manuela Donalisio, Federica Leone, Andrea Civra, Rita Spagnolo, Ozgen Ozer, David Lembo, Roberta Cavalli
Acyclovir is not a good candidate for passive permeation since its polarity and solubility limit is partitioning into the stratum corneum. This work aims to develop a new topical formulation for the acyclovir delivery. New chitosan nanospheres (NS) were prepared by a modified nano-emulsion template method. Chitosan NS were characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), and an in vitro release study. The in vitro skin permeation experiment was carried out using Franz cells and was equipped with porcine skin...
April 10, 2018: Pharmaceutics
Ha S Nguyen, Ahmed J Awad, Saman Shabani, Ninh Doan
Glioblastoma is the most common, malignant primary tumor of the central nervous system. The average prognosis for life expectancy after diagnosis, with the triad of surgery, chemotherapy, and radiation therapy, is less than 1.5 years. Chemotherapy treatment is mostly limited to temozolomide. In this paper, the authors review an emerging, novel drug called acid ceramidase, which targets glioblastoma. Its role in cancer treatment in general, and more specifically, in the treatment of glioblastoma, are discussed...
April 9, 2018: Pharmaceutics
Evert Fuenmayor, Martin Forde, Andrew V Healy, Declan M Devine, John G Lyons, Christopher McConville, Ian Major
Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more) of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more) of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms...
April 2, 2018: Pharmaceutics
Roberto Iacone, Clelia Scanzano, Anna D'Isanto, Andrea Vitalone, Ignazio Frangipane, Mariana D'Angeli, Lidia Santarpia, Franco Contaldo
Metabolic acidosis and metabolic bone disease are frequent complications in patients on parenteral nutrition (PN). A common contributor to these complications could be a daily high renal acid load. This study aims to find a method for predicting the potential total acid load (PTAL) and the pH of the compounded parenteral nutrition mixtures. The pH and titratable acidity (TA) of fifty compounded mixtures were measured. The potential metabolic acid load (PMAL) was calculated by considering the amount of nutrients that are acid producers and consumers...
April 2, 2018: Pharmaceutics
Blessing Atim Aderibigbe, Buhle Buyana
Alginate is a biopolymer used in a variety of biomedical applications due to its favourable properties, such as biocompatibility and non-toxicity. It has been particularly attractive in wound healing applications to date. It can be tailored to materials with properties suitable for wound healing. Alginate has been used to prepare different forms of materials for wound dressings, such as hydrogels, films, wafers, foams, nanofibres, and in topical formulations. The wound dressings prepared from alginate are able to absorb excess wound fluid, maintain a physiologically moist environment, and minimize bacterial infections at the wound site...
April 2, 2018: Pharmaceutics
Anusha Balla, Kwan Hyung Cho, Yu Chul Kim, Han-Joo Maeng
A simple, sensitive, and reliable reversed-phase, Ultra-High-Pressure Liquid Chromatography (UHPLC) coupled with a Diode Array Detector (DAD) method for the simultaneous determination of Procainamide (PA) and its major metabolite, N -acetylprocainamide (NAPA), in rat plasma was developed and validated. A simple deproteinization method with methanol was applied to the rat plasma samples, which were analyzed using UHPLC equipped with DAD at 280 nm, and a Synergi™ 4 µm polar, reversed-phase column using 1% acetic acid (pH 5...
March 30, 2018: Pharmaceutics
Blessing Atim Aderibigbe
In situ-based gel drug delivery systems that can bypass the blood-brain barrier, deliver the therapeutics to the desired site, reduce peripheral toxicity and control drug release kinetics have been developed. Some of the therapeutics used to treat neurological diseases suffer from poor bioavailability. Preclinical reports from several researchers have proven that the delivery of drugs to the brain via the nose-to-brain route using in situ gels holds great promise. However, safety issues on the toxicity of the nasal mucosa, transportation of the drugs to specific brain regions and determination of the required dose are factors that must be considered when designing these gels...
March 30, 2018: Pharmaceutics
Alessandro Dalpiaz, Barbara Pavan
Although several viruses can easily infect the central nervous system (CNS), antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs). These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1), multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5), and breast cancer resistance protein (ABCG2 or BCRP)...
March 26, 2018: Pharmaceutics
Federica Rinaldi, Patrizia N Hanieh, Lik King Nicholas Chan, Livia Angeloni, Daniele Passeri, Marco Rossi, Julie Tzu-Wen Wang, Anna Imbriano, Maria Carafa, Carlotta Marianecci
The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were also studied by atomic force microscopy (AFM)...
March 22, 2018: Pharmaceutics
Yang Wei, Yu-Han Chang, Chung-Jui Liu, Ren-Jei Chung
The susceptibility of guided bone regeneration (GBR) material to infection by pathogens at wound sites during bone healing has often been overlooked. The objective of this study was the synthesis and characterization of a potential material for antibacterial GBR application. In the current study, the mechanical strength and biocompatibility of a composite restoration material-made of oxidized hyaluronic acid (HA)/type I collagen hydrogel integrated with tricalcium phosphate (β-TCP) using a natural crosslinking agent, oligomeric proanthocyanidins (OPCs)-were evaluated...
March 21, 2018: Pharmaceutics
Emily S Mohn, Hua J Kern, Edward Saltzman, Susan H Mitmesser, Diane L McKay
The long-term use of prescription and over-the-counter drugs can induce subclinical and clinically relevant micronutrient deficiencies, which may develop gradually over months or even years. Given the large number of medications currently available, the number of research studies examining potential drug-nutrient interactions is quite limited. A comprehensive, updated review of the potential drug-nutrient interactions with chronic use of the most often prescribed medications for commonly diagnosed conditions among the general U...
March 20, 2018: Pharmaceutics
Poovizhi Ponnammal, Parijat Kanaujia, Yin Yani, Wai Kiong Ng, Reginald B H Tan
In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w / w . Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form...
March 16, 2018: Pharmaceutics
Fabio Sonvico, Adryana Clementino, Francesca Buttini, Gaia Colombo, Silvia Pescina, Silvia Stanisçuaski Guterres, Adriana Raffin Pohlmann, Sara Nicoli
In the field of nasal drug delivery, nose-to-brain delivery is among the most fascinating applications, directly targeting the central nervous system, bypassing the blood brain barrier. Its benefits include dose lowering and direct brain distribution of potent drugs, ultimately reducing systemic side effects. Recently, nasal administration of insulin showed promising results in clinical trials for the treatment of Alzheimer's disease. Nanomedicines could further contribute to making nose-to-brain delivery a reality...
March 15, 2018: Pharmaceutics
Poonam Parashar, Meena Rathor, Monika Dwivedi, Shubhini A Saraf
Lung carcinoma is the most common cancer in men and second in women (preceded by breast cancer) worldwide. Around 1 in 10 of all cancers diagnosed in men, lung cancer contributed to a total fraction of 20% cancer deaths. Naringenin (NAR) is well known for its chemopreventive properties since ancient times but lacks an appropriate delivery carrier. The objective of present study was to expand the functionality of naringenin loaded poly caprolactone (PCL) nanoparticles in terms of release, chemoprevention and therapeutics...
March 12, 2018: Pharmaceutics
Sultana Mehbuba Hossain, Ezharul Hoque Chowdhury
Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. We aimed to chemically modify carbonate apatite (CA) with Krebs cycle intermediates, such as citrate and succinate in order to control the growth of the resultant particles to more efficiently carry and transport the anticancer drug into the cancer cells...
March 11, 2018: Pharmaceutics
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