Open AccessArticle
Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability
Pharmaceutics 2017, 9(3), 22; doi:10.3390/pharmaceutics9030022 (registering DOI) -
Abstract
Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving
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Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young’s Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m2. FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application. Full article
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Open AccessArticle
Surface-Modification of Carbonate Apatite Nanoparticles Enhances Delivery and Cytotoxicity of Gemcitabine and Anastrozole in Breast Cancer Cells
Pharmaceutics 2017, 9(2), 21; doi:10.3390/pharmaceutics9020021 -
Abstract
pH sensitive nanoparticles of carbonate apatite (CA) have been proven to be effective delivery vehicles for DNA, siRNAs and proteins. More recently, conventional anti-cancer drugs, such as doxorubicin, methotrexate and cyclophosphamide have been successfully incorporated into CA for intracellular delivery to breast cancer
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pH sensitive nanoparticles of carbonate apatite (CA) have been proven to be effective delivery vehicles for DNA, siRNAs and proteins. More recently, conventional anti-cancer drugs, such as doxorubicin, methotrexate and cyclophosphamide have been successfully incorporated into CA for intracellular delivery to breast cancer cells. However, physical and chemical properties of drug molecules appeared to affect their interactions with CA, with hydrophillic drug so far exhibiting better binding affinity and cellular uptakes compared to hydrophobic drugs. In this study, anastrozole, a non-steroidal aromatase inhibitor which is largely hydrophobic, and gemcitabine, a hydrophilic nucleoside inhibitor were used as solubility models of chemotherapy drug. Aggregation tendency of poorly soluble drugs resulting in larger particle-drug complex size might be the main factor hindering their delivery effectiveness. For the first time, surface modification of CA with poly(ethylene glycol) (PEG) has shown promising result to drastically reduce anastrozole- loaded CA particle size, from approximately 1000 to 500 nm based on zeta sizer analysis. Besides PEG, a cell specific ligand, in this case fibronectin, was attached to the particles in order to facilitate receptor mediated endocytosis based on fibronectin–integrin interaction. High-performance liquid chromatography (HPLC) was performed to measure uptake of the drugs by breast cancer cells, revealing that surface modification increased the drug uptake, especially for the hydrophobic drug, compared to the uncoated particles and the free drug. In vitro chemosensitivity assay and in vivo tumor regression study also showed that coated apatite/drug nanoparticle complexes presented higher cytotoxicity and tumor regression effects than uncoated apatite/drug nanoparticles and free drugs, indicating that surface modification successfully created optimum particles size with the consequence of more effective uptake along with favorable pharmacokinetics of the particles. Full article
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Open AccessArticle
An Evaluation of the Binding Strength of Okra Gum and the Drug Release Characteristics of Tablets Prepared from It
Pharmaceutics 2017, 9(2), 20; doi:10.3390/pharmaceutics9020020 -
Abstract
The aim of this study is to evaluate the adhesion ability of okra gum, which is gaining popularity as a tablet binder. For this purpose, gum was extracted from okra pods, and the binding strength of different concentrations (1%, 3%, and 5%) was
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The aim of this study is to evaluate the adhesion ability of okra gum, which is gaining popularity as a tablet binder. For this purpose, gum was extracted from okra pods, and the binding strength of different concentrations (1%, 3%, and 5%) was determined quantitatively. Additionally, naproxen sodium tablets were prepared by using okra gum as a binder and were evaluated for their properties including hardness, friability, disintegration time, and dissolution rate. The binding strength values were compared with that of pre-gelatinized starch, a commonly used tablet binder. The results from universal testing machine indicate that the binding strengths of all dispersions of okra increase as the concentration increases from 1% to 5% and ranges from 2.5 to 4.5 N, which are almost twice a high as those of pre-gelatinized starch. The tablets prepared with okra gum have shown good mechanical strength with hardness values of 7–8.5 kg/cm2 and a friability <1%, comparable to tablets prepared with starch. The disintegration time was longer (7.50 min with okra gum and 5.05 min with starch paste), and the drug release from these tablets was slower than the formulations with starch. The higher binding ability of okra gum probably linked with its chemical composition as it mainly contains galactose, rhamnose, and galacturonic acid. This study concludes that okra gum is a better binder than pre-gelatinized starch, it might be explored in future for introduction as a cost-effective binder in the pharmaceutical industry. Full article
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Open AccessArticle
Stability Study of Sunscreens with Free and Encapsulated UV Filters Contained in Plastic Packaging
Pharmaceutics 2017, 9(2), 19; doi:10.3390/pharmaceutics9020019 -
Abstract
Sunscreens play a fundamental role in skin cancer prevention and in protection against photo-aging. UV filters are often photo-unstable, especially in relation to their vehicles and, being lipophilic substances, they are able to interact with plastic packaging. Finally, UV filter stability can be
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Sunscreens play a fundamental role in skin cancer prevention and in protection against photo-aging. UV filters are often photo-unstable, especially in relation to their vehicles and, being lipophilic substances, they are able to interact with plastic packaging. Finally, UV filter stability can be significantly affected by the routine use of the product at high temperatures. This work aims to study the stability of sunscreen formulations in polyethylene packaging. Butyl methoxydibenzoylmethane and octocrylene, both in a free form and as encapsulated filters were chosen as UV filters. Stability evaluations were performed both in the packaging and on the formulations. Moreover, a further two non-destructive techniques, near-infrared (NIR) spectroscopy and a multiple light scattering technique, were also used to evaluate the stability of the formulation. Results demonstrated clearly that all of the pack underwent significant changes in its elastic/plastic behavior and in external color after solar irradiation. From the evaluation of the extractable profile of untreated and treated packaging material an absorption of 2-phenoxyethanol and octocrylene were shown. In conclusion, the results highlighted clearly that a reduction of the UV filter in the formulation packed in high-density polyethylene/low-density polyethylene (HDPE/LDPE) material can occur over time, reducing the protective effect of the product when applied to the skin. Full article
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Open AccessArticle
Quality Attributes and In Vitro Bioequivalence of Different Brands of Amoxicillin Trihydrate Tablets
Pharmaceutics 2017, 9(2), 18; doi:10.3390/pharmaceutics9020018 -
Abstract
Bacterial resistance and antibiotic drug effectiveness can be related to administering generic products with a subtherapeutic dose or poor in vivo drug release. The aim of this study was to investigate whether locally marketed amoxicillin tablets have the required chemical and physical attributes,
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Bacterial resistance and antibiotic drug effectiveness can be related to administering generic products with a subtherapeutic dose or poor in vivo drug release. The aim of this study was to investigate whether locally marketed amoxicillin tablets have the required chemical and physical attributes, including in vitro bioequivalence performance. Five generic products (T1, T2, T3, T4, and T5) containing combination of amoxicillin trihydrate and potassium clavulanate as 1 g strength present in immediate release tablets were compared to the reference listed drug product Augmentin® (R) for weight variation, friability, resistance to crushing, and chemical content of amoxicillin. Difference (ƒ1) and similarity (ƒ2) factors were calculated to assess in vitro bioequivalence requirements. The tablets from different products have shown compliance with the pharmacopeial requirements of the performed tests. The measured resistance to crushing of tablets did not influence the dissolution time. Three generic products released more than 85% of amoxicillin by the first 15 min as did the reference product and were considered as bioequivalent products. T1 and T4 had ƒ1 values of 16.5% and 25.4% respectively and their ƒ2 values were 44.5 and 34.6 respectively, indicating failure to meet in vitro bioequivalence requirements. Tablet formulations can play an important role in achieving bioequivalence. Independent investigations such as this study serve as an important tool to reveal possible inferior or noncompliant products that may find their way to the market. Full article
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Open AccessArticle
Optimizing Prednisolone Loading into Distiller’s Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery
Pharmaceutics 2017, 9(2), 17; doi:10.3390/pharmaceutics9020017 -
Abstract
Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery
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Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT. Full article
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Open AccessArticle
Accessing Mefenamic Acid Form II through High-Pressure Recrystallisation
Pharmaceutics 2017, 9(2), 16; doi:10.3390/pharmaceutics9020016 -
Abstract
High-pressure crystallisation has been successfully used as an alternative technique to prepare Form II of a non-steroidal anti-inflammatory drug, mefenamic acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was grown at 0.3 GPa from an ethanolic solution by
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High-pressure crystallisation has been successfully used as an alternative technique to prepare Form II of a non-steroidal anti-inflammatory drug, mefenamic acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was grown at 0.3 GPa from an ethanolic solution by using a diamond anvil cell. A comparison of the crystal structures shows that the efficient packing of molecules in Form II was enabled by the structural flexibility of MA molecules. Compression studies performed on a single crystal of Form I resulted in a 14% decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which was confirmed by the results of crystallisation at high pressure. Full article
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Open AccessArticle
Folate Decorated Nanomicelles Loaded with a Potent Curcumin Analogue for Targeting Retinoblastoma
Pharmaceutics 2017, 9(2), 15; doi:10.3390/pharmaceutics9020015 -
Abstract
The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability
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The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability of CDF. For this purpose, amphiphilic poly(styrene-co-maleic acid)-conjugated-folic acid (SMA-FA) was synthesized and utilized to improve the aqueous solubility of a highly hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery to folate overexpressing cancers. The SMA-FA conjugate was first synthesized and characterized by 1H NMR, FTIR and DSC. Furthermore, the chromatographic condition (HPLC) for estimating CDF was determined and validated. The formulation was optimized to achieve maximum entrapment of CDF. The particle size of the micelles was measured and confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Cytotoxicity studies were conducted on (Y-79 and WERI-RB) retinoblastoma cells. Results showed that the solubility of CDF could be increased with the newly-synthesized polymer, and the entrapment efficiency was >85%. The drug-loaded nanomicelles exhibited an appropriate size of <200 nm and a narrow size distribution. The formulation did not show any adverse cytotoxicity on a human retinal pigment epithelial cell (ARPE-19), indicating its safety. However, it showed significant cell killing activity in both Y-79 and WERI-RB retinoblastoma cell lines, indicating its potency in killing cancer cells. In conclusion, the folic acid-conjugated SMA loaded with CDF showed promising potential with high safety and pronounced anticancer activity on the tested retinoblastoma cell lines. The newly-formulated targeted nanomicelles thus could be a viable option as an alternative approach to current retinoblastoma therapies. Full article
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Open AccessReview
What Does It “Mean”? A Review of Interpreting and Calculating Different Types of Means and Standard Deviations
Pharmaceutics 2017, 9(2), 14; doi:10.3390/pharmaceutics9020014 -
Abstract
Typically, investigations are conducted with the goal of generating inferences about a population (humans or animal). Since it is not feasible to evaluate the entire population, the study is conducted using a randomly selected subset of that population. With the goal of using
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Typically, investigations are conducted with the goal of generating inferences about a population (humans or animal). Since it is not feasible to evaluate the entire population, the study is conducted using a randomly selected subset of that population. With the goal of using the results generated from that sample to provide inferences about the true population, it is important to consider the properties of the population distribution and how well they are represented by the sample (the subset of values). Consistent with that study objective, it is necessary to identify and use the most appropriate set of summary statistics to describe the study results. Inherent in that choice is the need to identify the specific question being asked and the assumptions associated with the data analysis. The estimate of a “mean” value is an example of a summary statistic that is sometimes reported without adequate consideration as to its implications or the underlying assumptions associated with the data being evaluated. When ignoring these critical considerations, the method of calculating the variance may be inconsistent with the type of mean being reported. Furthermore, there can be confusion about why a single set of values may be represented by summary statistics that differ across published reports. In an effort to remedy some of this confusion, this manuscript describes the basis for selecting among various ways of representing the mean of a sample, their corresponding methods of calculation, and the appropriate methods for estimating their standard deviations. Full article
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Open AccessReview
Liposomal Formulations in Clinical Use: An Updated Review
Pharmaceutics 2017, 9(2), 12; doi:10.3390/pharmaceutics9020012 -
Abstract
Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their
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Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clinical products, e.g., Doxil®, Ambisome®, DepoDur™, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam™ Technology, Stealth technology, etc., the formulation aspects of clinically used products and ongoing clinical trials on liposomes. Full article
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Open AccessArticle
Blend Hydrogel Microspheres of Carboxymethyl Chitosan and Gelatin for the Controlled Release of 5-Fluorouracil
Pharmaceutics 2017, 9(2), 13; doi:10.3390/pharmaceutics9020013 -
Abstract
Carboxymethyl chitosan (CMCS) was synthesized and blended with gelatin (GE) to prepare hydrogel microspheres by w/o emulsion cross-linking in the presence of glutaraldehyde (GA), which acted as a cross-linker. 5-Fluorouracil (5-FU) was encapsulated to investigate its controlled release (CR) characteristics in acidic (pH
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Carboxymethyl chitosan (CMCS) was synthesized and blended with gelatin (GE) to prepare hydrogel microspheres by w/o emulsion cross-linking in the presence of glutaraldehyde (GA), which acted as a cross-linker. 5-Fluorouracil (5-FU) was encapsulated to investigate its controlled release (CR) characteristics in acidic (pH 1.2) and alkaline (pH 7.4) buffer media. The microspheres which formed were spherical in nature, with smooth surfaces, as judged by the scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) confirmed the carboxymethylation of CS and the chemical stability of 5-FU in the formulations. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the physical state and molecular level dispersion of 5-FU. Equilibrium swelling of microspheres was performed in water, in order to understand the water uptake properties. The in vitro release of 5-FU was extended up to 12 h in pH 7.4 phosphate buffer, revealing an encapsulation efficiency of 72%. The effects of blend composition, the extent of cross-linking, and initial drug loading on the in vitro release properties, were investigated. When analyzed through empirical equations, the release data suggested a non-Fickian transport mechanism. Full article
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Open AccessArticle
A Robust Liquid Chromatographic Method for Confirmation of Drug Stability of Azithromycin in Bulk Samples, Tablets and Suspensions
Pharmaceutics 2017, 9(1), 11; doi:10.3390/pharmaceutics9010011 -
Abstract
A simple, isocratic and robust RP-HPLC method for the analysis of azithromycin was developed, validated and applied for the analysis of bulk samples, tablets and suspensions. The optimum chromatographic conditions for separation were established as a mobile phase comprised of acetonitrile-0.1 M KH
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A simple, isocratic and robust RP-HPLC method for the analysis of azithromycin was developed, validated and applied for the analysis of bulk samples, tablets and suspensions. The optimum chromatographic conditions for separation were established as a mobile phase comprised of acetonitrile-0.1 M KH2PO4 pH 6.5–0.1 M tetrabutyl ammonium hydroxide pH 6.5-water (25:15:1:59 v/v/v/v) delivered at a flow rate of 1.0 mL/min. The stationary phase consisted of reverse-phase XTerra® (250 mm × 4.6 mm i.d., 5 µm particle size) maintained at a temperature of 43 °C with a UV detection at 215 nm. The method was found to be linear in the range 50%–150% (r2 = 0.997). The limits of detection and quantification were found to be 0.02% (20 µg) and 0.078% (78 µg), respectively, with a 100.7% recovery of azithromycin. Degradation products of azithromycin in acidic and oxidative environments at 37 °C were resolved from the active pharmaceutical ingredient and thus the method is fit for the purpose of drug stability confirmation. Full article
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Open AccessReview
Polypharmacy in Zoological Medicine
Pharmaceutics 2017, 9(1), 10; doi:10.3390/pharmaceutics9010010 -
Abstract
Polypharmacy is a term that describes the inappropriate, concurrent use of multiple drugs in an individual patient. Zoological medicine practitioners must take approved agents (veterinary or human) and extrapolate their use to non-approved species often with little species-specific pharmacological evidence to support their
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Polypharmacy is a term that describes the inappropriate, concurrent use of multiple drugs in an individual patient. Zoological medicine practitioners must take approved agents (veterinary or human) and extrapolate their use to non-approved species often with little species-specific pharmacological evidence to support their decisions. When considering polypharmacy, even less information exists concerning multi-drug pharmacokinetics, pharmacodynamics, or potential drug-drug interactions in non-domestic species. Unfortunately, captive, zoological species are susceptible, just like their domestic counterparts, to chronic diseases and co-morbidities that may lead to the usage of multiple drugs. Polypharmacy is a recognized and important issue in human medicine, as well as an emerging issue for veterinarians; thus, this paper will discuss the novel, potential risks of polypharmacy in zoological medicine. Hopefully, this discussion will help bring the attention of veterinarians to this issue and serve as an interesting discussion topic for pharmacologists in general. Full article
Open AccessReview
Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target
Pharmaceutics 2017, 9(1), 9; doi:10.3390/pharmaceutics9010009 -
Abstract
Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney,
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Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal ischemia/reperfusion (I/R) injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future. Full article
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Open AccessArticle
Lobular Distribution and Variability in Hepatic ATP Binding Cassette Protein B1 (ABCB1, P-gp): Ontogenetic Differences and Potential for Toxicity
Pharmaceutics 2017, 9(1), 8; doi:10.3390/pharmaceutics9010008 -
Abstract
The ATP Binding Cassette B1 (ABCB1) transporter has critical roles in endo- and xenobiotic efficacy and toxicity. To understand population variability in hepatic transport we determined ABCB1 mRNA and protein levels in total liver lysates sampled from 8 pre-defined sites (n =
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The ATP Binding Cassette B1 (ABCB1) transporter has critical roles in endo- and xenobiotic efficacy and toxicity. To understand population variability in hepatic transport we determined ABCB1 mRNA and protein levels in total liver lysates sampled from 8 pre-defined sites (n = 24, 18–69 years), and in S9 from randomly acquired samples (n = 87, 7 days–87 years). ABCB1 levels did not differ significantly throughout individual livers and showed 4.4-fold protein variation between subjects. Neither mRNA nor protein levels varied with sex, ethnicity, obesity or triglycerides in lysates or S9 (that showed the same relationships), but protein levels were lower in pediatric S9 (p < 0.0001), with 76% of adult ABCB1 present at birth and predicted to mature in 5 years. Pediatric total liver lysates were not available. In summary, opportunistic collection for studying human hepatic ABCB1 is acceptable. Additionally, ABCB1 may be lower in children, indicating differential potential for toxicity and response to therapy in this special population. Full article
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Open AccessArticle
Investigation of Drug–Polymer Compatibility Using Chemometric-Assisted UV-Spectrophotometry
Pharmaceutics 2017, 9(1), 7; doi:10.3390/pharmaceutics9010007 -
Abstract
A simple chemometric-assisted UV-spectrophotometric method was used to study the compatibility of clindamycin hydrochloride (HC1) with two commonly used natural controlled-release polymers, alginate (Ag) and chitosan (Ch). Standard mixtures containing 1:1, 1:2, and 1:0.5 w/w drug–polymer ratios were prepared and UV
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A simple chemometric-assisted UV-spectrophotometric method was used to study the compatibility of clindamycin hydrochloride (HC1) with two commonly used natural controlled-release polymers, alginate (Ag) and chitosan (Ch). Standard mixtures containing 1:1, 1:2, and 1:0.5 w/w drug–polymer ratios were prepared and UV scanned. A calibration model was developed with partial least square (PLS) regression analysis for each polymer separately. Then, test mixtures containing 1:1 w/w drug–polymer ratios with different sets of drug concentrations were prepared. These were UV scanned initially and after three and seven days of storage at 25 °C. Using the calibration model, the drug recovery percent was estimated and a decrease in concentration of 10% or more from initial concentration was considered to indicate instability. PLS models with PC3 (for Ag) and PC2 (for Ch) showed a good correlation between actual and found values with root mean square error of cross validation (RMSECV) of 0.00284 and 0.01228, and calibration coefficient (R2) values of 0.996 and 0.942, respectively. The average drug recovery percent after three and seven days was 98.1 ± 2.9 and 95.4 ± 4.0 (for Ag), and 97.3 ± 2.1 and 91.4 ± 3.8 (for Ch), which suggests more drug compatibility with an Ag than a Ch polymer. Conventional techniques including DSC, XRD, FTIR, and in vitro minimum inhibitory concentration (MIC) for (1:1) drug–polymer mixtures were also performed to confirm clindamycin compatibility with Ag and Ch polymers. Full article
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Open AccessEditorial
Acknowledgement to Reviewers of Pharmaceutics in 2016
Pharmaceutics 2017, 9(1), 6; doi:10.3390/pharmaceutics9010006 -
Open AccessFeature PaperReview
Veterinary Compounding: Regulation, Challenges, and Resources
Pharmaceutics 2017, 9(1), 5; doi:10.3390/pharmaceutics9010005 -
Abstract
The spectrum of therapeutic need in veterinary medicine is large, and the availability of approved drug products for all veterinary species and indications is relatively small. For this reason, extemporaneous preparation, or compounding, of drugs is commonly employed to provide veterinary medical therapies.
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The spectrum of therapeutic need in veterinary medicine is large, and the availability of approved drug products for all veterinary species and indications is relatively small. For this reason, extemporaneous preparation, or compounding, of drugs is commonly employed to provide veterinary medical therapies. The scope of veterinary compounding is broad and focused primarily on meeting the therapeutic needs of companion animals and not food-producing animals in order to avoid human exposure to drug residues. As beneficial as compounded medical therapies may be to animal patients, these therapies are not without risks, and serious adverse events may occur from poor quality compounds or excipients that are uniquely toxic when administered to a given species. Other challenges in extemporaneous compounding for animals include significant regulatory variation across the global veterinary community, a relative lack of validated compounding formulas for use in animals, and poor adherence by compounders to established compounding standards. The information presented in this article is intended to provide an overview of the current landscape of compounding for animals; a discussion on associated benefits, risks, and challenges; and resources to aid compounders in preparing animal compounds of the highest possible quality. Full article
Open AccessArticle
Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier
Pharmaceutics 2017, 9(1), 4; doi:10.3390/pharmaceutics9010004 -
Abstract
For the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. The SS-bonded nanocapsules
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For the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. The SS-bonded nanocapsules exhibited a very slow release of DOX under an extracellular environment because the cationic PLL membrane acted as an electrostatic barrier against the protonated DOX molecules. However, increasing the glutathione concentration to the intracellular level facilitated the immediate release of DOX through the collapse of nanocapsules by the spontaneous cleavage of SS bonds. SS-bonded nanocapsules also escaped from the endosome by the buffering effect of PAMAM dendrons, and DOX delivery into the cytoplasm was achieved. Furthermore, DOX molecules delivered by SS-bonded nanocapsules exhibited an effective in vitro anticancer effect to HeLa cells. Full article
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Open AccessArticle
Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells
Pharmaceutics 2017, 9(1), 3; doi:10.3390/pharmaceutics9010003 -
Abstract
Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in
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Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP) activity, presumed to reflect expression of various hepatic MRPs, including MRP2. By contrast, they failed to display functional activities of the uptake transporters sodium taurocholate co-transporting polypeptide (NTCP), organic anion-transporting polypeptides (OATPs) and organic cation transporter 1 (OCT1), and of the canalicular transporters P-glycoprotein and breast cancer resistance protein (BCRP). Concomitantly, mRNA expressions of various sinusoidal and canalicular hepatic drug transporters were not detected (NTCP, OATP1B1, organic anion transporter 2 (OAT2), OCT1 and bile salt export pump) or were found to be lower (OATP1B3, OATP2B1, multidrug and toxin extrusion protein 1, BCRP and MRP3) in hepatoma HuH-7 cells than those found in human hepatocytes, whereas other transporters such as OAT7, MRP4 and MRP5 were up-regulated. HuH-7 cells additionally exhibited farnesoid X receptor (FXR)- and nuclear factor erythroid 2-related factor 2 (Nrf2)-related up-regulation of some transporters. Such data indicate that HuH-7 cells, although expressing rather poorly some main hepatic drug transporters, may be useful for investigating interactions of drugs with MRPs, notably MRP2, and for studying FXR- or Nrf2-mediated gene regulation. Full article
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