0000000000277014
AUTHOR
Teresa María Garrigues
Metodología Aprendizaje-Servicio adaptada al confinamiento por COVID-19: Utilización en la prevención de adicciones
[EN] In the Faculty of Pharmacy, the activity "Specific Service Learning (SL)" is carried out. SL allows a team of the center's teaching staff to work voluntarily and in a coordinated manner in the training of people who study the five degrees taught at the center. The suspension of all face-to-face educational and training activities in March 2020 due to the COVID-19 pandemic completely altered the continuation of the tasks and actions related to the SL projects. The objective of this work is to describe the design and implementation of a SL project on addictions that had to be adapted to the digital field for a receiving group with certain characteristics. It will also be described how a …
Activity–Bioavailability balance in Oral Drug Development for a Selected Group of 6‐Fluoroquinolones
Abstract A nomogram is proposed to select the best candidate in drug development studies with quinolones and is intended to substitute other possible models. The nomogram is referred to as an activity–bioavailability balance (ABB) because it includes the following two criteria: ABB= 1 / gm MIC ( drug candidate ) 1 /gm MIC ( ciprofloxacin ) · F calc \( drug candidate \) F calc ( ciproflaxacin ) . The in vitro activity of a group of 4′ N ‐alkyl‐ciprofloxacin derivatives was determined together with that of ciprofloxacin, initially against some reference strains and subsequently against 159 clinical isolates of eight selected species. The inverse of the geometric mean of the lowest concentrati…
PAMPA—a drug absorption in vitro model
Parallel artificial membrane permeability assay (PAMPA) was used to measure the effective permeability, P(e), as a function of pH from 4 to 10, of 17 fluoroquinolones, including three congeneric series with systematically varied alkyl chain length at the 4'N-position of the piperazine residue. The permeability values spanned over three orders of magnitude. The intrinsic permeability, P(o), and the membrane permeability, P(m), were determined from the pH dependence of the effective permeability. The pK(a) values were determined potentiometrically. The PAMPA method employed stirring, adjusted such that the unstirred water layer (UWL) thickness matched the 30-100 microm range estimated to be i…
Compared effects of synthetic and natural bile acid surfactants on xenobiotic absorption I. Studies with polysorbate and taurocholate in rat colon
Some expected differences between synthetic and natural bile acid surfactants relative to their influences on xenobiotic absorption are briefly outlined on the basis of literature data. Then, experimental work is presented which shows that these differences exist and that they can be even more relevant than suspected. Absorption tests were developed in rat colon in situ with polysorbate (synthetic) and sodium taurocholate (natural) surfactants, using a homologous series of phenylalkylcarboxylic acids as test compounds. At the critical micelle concentration (CMC), the two previously reported actions of synthetic surfactants on xenobiotic absorption (i.e. the increase in absorbing membrane po…
Transintestinal secretion of ciprofloxacin, grepafloxacin and sparfloxacin: in vitro and in situ inhibition studies.
The influence of the secretion process on the absorption of ciprofloxacin, grepafloxacin and sparfloxacin has been evaluated by means of inhibition studies. Two well known P-glycoprotein inhibitors (cyclosporine, verapamil), a mixed inhibitor of P-glycoprotein and the organic cation transporter OCT1 (quinidine) and a well established MRP substrate (p-aminohipuric acid) have been selected in order to distinguish the possible carriers implicated. An in situ rat gut perfusion model and CACO-2 permeability studies are used. Both methods suggest the involvement of several types of efflux transporters for every fluoroquinolone. The relevance of the secretory pathway depends on the intrinsic perme…
Labetalol absorption kinetics: Rat small intestine and colon studies
Labetalol is a widely used drug for the management of hypertension, which is preferably administered by the oral route despite its low bioavailability. The objective of this study is to ascertain the mechanisms underlying its absorption as an approach to help in predicting the influence of dosage changes, possible drug-drug and drug-fruit juice interactions. Perfusion experiments have been performed in rats in two sites of absorption: the intestine and the colon. The nonlinearity of the process has been established by means of the assay of a wide range of concentrations (2-2000 microM). Fitting of the concentration versus time data allows the estimation of passive diffusion constant in the …
Innocampus Explora: Nuevas formas de comunicar ciencia
[EN] Innocampus Explora aims to show the students of the Burjassot-Paterna campus of the Universitat de València how the different scientific degrees are interrelated. To do this we propose activities in which students and teachers work together to cover the interdisciplinary nature of science, both in everyday and professional issues. Throughout this course the activities developed relate to new ways to communicate science. With the development of this project we contribute to a transversal quality education for all the participating students.
Polymeric microcontainers improve oral bioavailability of furosemide.
Microcontainers with an inner diameter of 223 μm are fabricated using the polymer SU-8, and evaluated in vitro, in situ and in vivo for their application as an advanced oral drug delivery system for the poorly water soluble drug furosemide. An amorphous sodium salt of furosemide (ASSF) is filled into the microcontainers followed by applying a lid using Eudragit L100. It is possible to control the drug release in vitro, and in vitro absorption studies show that the microcontainers are not a hindrance for absorption of ASSF. In situ perfusion studies in rats are performed with ASSF-filled microcontainers coated with Eudragit and compared to a furosemide solution. The absorption rate constant …
Caffeine analysis and extraction from a topical cream intended for UV-skin protection
Made available in DSpace on 2021-06-25T10:16:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 This study aimed to develop and validate a method for the analysis of caffeine in complex cosmetic samples, such as sunscreens. Besides, an extraction method of caffeine from coffee oil and from creams, which contains both lipophilic and hydrophilic components, has been developed. The method to analyze caffeine was developed using an isocratic pump, Waters 1515 and an automatic injector Perkin-Elmer Series 200 and an UV detector Perkin-Elmer. As stationary phase, Kromasil C-18 (150 × 4.6 mm ID with particle size of 5 µm) column was used and a mixture of water (pH 4.00)/acetonitrile (…
Cubic Microcontainers Improve In Situ Colonic Mucoadhesion and Absorption of Amoxicillin in Rats
An increased interest in colonic drug delivery has led to a higher focus on the design of delivery devices targeting this part of the gastrointestinal tract. Microcontainers have previously facilitated an increase in oral bioavailability of drugs. The surface texture and shape of microcontainers have proven to influence the mucoadhesion ex vivo. In the present work, these findings were further investigated using an in situ closed-loop perfusion technique in the rat colon, which allowed for simultaneous evaluation of mucoadhesion of the microcontainers as well as drug absorption. Cylindrical, triangular and cubic microcontainers, with the same exterior surface area, were evaluated based on i…
Innocampus Explora: Una aproximación multidisciplinar a la problemática ambiental
[ES] Presentamos las actividades del proyecto de innovación Innocampus Explora desarrollado en el campus de Burjassot-Paterna de la Universitat de València y cuyo objetivo principal es mostrar la interrelación existente entre los diferentes grados científicos y técnicos del campus. En la presente anualidad, el equipo de trabajo integrado por estudiantes y profesores de todos las facultades y escuelas del campus de Burjassot-Paterna, ha desarrollado actividades en torno a la problemática medioambiental. Una visión transversal e interdisciplinar de los problemas de los usos del plástico y de la energía nuclear que enlaza con varios de los Objetivos de Desarrollo Sostenible (ODS) dictados por …
Mathematical modelling of in situ and in vitro efflux of ciprofloxacin and grepafloxacin
Abstract The efflux process due to p-glycoprotein-like mechanisms of ciprofloxacin (CIP) and grepafloxacin (GRX) has been studied “in situ” in rats and “in vitro” in Caco-2 cells. The results were modelled by a curve fitting procedure which allowed the characterization of the passive (Pd) and carrier mediated parameters (Vm and Km) from the raw data without initial velocities estimation. CIP absorption in rat was characterized as a passive diffusion at the assayed concentrations. Although the involvement of an efflux transporter cannot be ruled out, its relevance in the transport of the fluoroquinolone is negligible. In GRX absorption, an efflux process is implicated and it is detected in b…
Emprendimiento Social en Ciencias de la Salud: Creación del Aula ApS-Salud en la Facultad de Farmacia de la Universitat de València.
[EN] Service-Learning (SL) aligned to Sustainable Development Goals (SDG) is an educational tool that is used in the Faculty of Pharmacy of the University of Valencia in an interdisciplinary way. The Study Plans of the five Degrees taught in this center do not explicitly cover subjects or content in entrepreneurship, business creation and / or development of projects that may originate business.However, there are certain contents that are oriented in a different way could be used to promote these abilities in students. SL-Health Classroom aims to cover this aspect and has been created with the aim of designing, planning and executing SL projects that serve as a driving idea for a subsequent…
Skin-PAMPA: a new method for fast prediction of skin penetration.
The goal of this study was to develop a quick, reliable, and cost-effective permeability model for predicting transdermal penetration of compounds. The Parallel Artificial Membrane Permeability Assay (PAMPA) was chosen for this purpose, as it already has been successfully used for estimating passive gastrointestinal absorption and blood-brain barrier permeability. To match the permeability of the rate-limiting barrier in human skin, synthetic certramides, which are analogs of the ceramides present in the stratum corneum, were selected for the skin-PAMPA model. The final skin-PAMPA membrane lipid mixture (certramide, free fatty acid, and cholesterol) was selected and optimized based on data …
Kinetic modelling of passive transport and active efflux of a fluoroquinolone across Caco-2 cells using a compartmental approach in NONMEM.
The purpose was to develop a general mathematical model for estimating passive permeability and efflux transport parameters from in vitro cell culture experiments. The procedure is applicable for linear and non-linear transport of drug with time,10 or10% of drug transport, negligible or relevant back flow, and would allow the adequate correction in the case of relevant mass balance problems. A compartmental kinetic approach was used and the transport barriers were described quantitatively in terms of apical and basolateral clearances. The method can be applied when sink conditions are not achieved and it allows the evaluation of the location of the transporter and its binding site. In this …
The Use of Rule-Based and QSPR Approaches in ADME Profiling: A Case Study on Caco-2 Permeability.
During the early ADME profiling the development of simple, interpretable and reliable in silico tools is very important. In this study, rule-based and QSPR approaches were investigated using a large Caco-2 permeability database. Three permeability classes were determined: high (H), moderate (M) and low (L). The main physicochemical properties related with permeability were ranked as follows: Polar Surface Area (PSA)>Lipophilicity (logP/logD)>Molecular Weight (MW)>number of Hydrogen Bond donors and acceptors>Ionization State>number of Rotatable Bonds>number of Rings. The best rule, based on the combination of PSA-MW-logD (3PRule), was able to identify the H, M and L classes with accuracy of …
Quantification of nortriptyline in plasma by HPLC and fluorescence detection
Abstract A simple, sensitive and specific high-performance liquid chromatography method has been developed for the determination of nortriptyline (NT) in plasma samples. The assay involved derivatization with 9H-fluoren-9-ylmethyl chloroformate (Fmoc-Cl) and isocratic reversed-phase (C 18 ) chromatography with fluorescence detection. The developed method required only 100 μl of plasma sample, deproteinized and derivatized in one step. Calibration curves were lineal over the concentration range of 5–5000 ng/ml. The derivatization reaction was performed at room temperature in 20 min and the obtained NT derivative was stable for at least 48 h at room temperature. The within-day and between-day…
QSAR Analysis of Hypoglycemic Agents Using the Topological Indices
The molecular topology model and discriminant analysis have been applied to the prediction of some pharmacological properties of hypoglycemic drugs using multiple regression equations with their statistical parameters. Regression analysis showed that the molecular topology model predicts these properties. The corresponding stability (cross-validation) studies performed on the selected prediction models confirmed the goodness of the fits. The method used for hypoglycemic activity selection was a linear discriminant analysis (LDA). We make use of the pharmacological distribution diagrams (PDDs) as a visualizing technique for the identification and selection of new hypoglycemic agents, and we …
Provisional Classification and in Silico Study of Biopharmaceutical System Based on Caco-2 Cell Permeability and Dose Number
Today, early characterization of drug properties by the Biopharmaceutics Classification System (BCS) has attracted significant attention in pharmaceutical discovery and development. In this direction, the present report provides a systematic study of the development of a BCS-based provisional classification (PBC) for a set of 322 oral drugs. This classification, based on the revised aqueous solubility and the apparent permeability across Caco-2 cell monolayers, displays a high correlation (overall 76%) with the provisional BCS classification published by World Health Organization (WHO). Current database contains 91 (28.3%) PBC class I drugs, 76 (23.6%) class II drugs, 97 (31.1%) class III d…
Cyanocobalamin Ultraflexible Lipid Vesicles: Characterization and In Vitro Evaluation of Drug-Skin Depth Profiles
Atopic dermatitis (AD) and psoriasis are the most common chronic inflammatory skin disorders, which importantly affect the quality of life of patients who suffer them. Among other causes, nitric oxide has been reported as part of the triggering factors in the pathogenesis of both conditions. Cyanocobalamin (vitamin B12) has shown efficacy as a nitric oxide scavenger and some clinical trials have given positive outcomes in its use for treating skin pathologies. Passive skin diffusion is possible only for drugs with low molecular weights and intermediate lipophilicity. Unfortunately, the molecular weight and hydrophilicity of vitamin B12 do not predict its effective diffusion through the skin…
Wistar rat skin as surrogate for human skin in nortriptyline hydrochloride patch studies
Six different matrices were prepared containing nortriptyline hydrochloride (NTH) with hydroxypropyl-methyl-cellulose as polymer. A mixture of transdermal enhancers was included as part of the vehicle. Diffusion studies were carried out through Wistar rat full thickness skin using Franz cells. They were compared with previously determined human heat separated epidermis in order to test if this animal can be used as model for in vivo assays. A linear correlation was obtained between NTH diffusion coefficients through both skin types (r2=0.996).
Validation of a biophysical drug absorption model by the PATQSAR system
Absorption rate constants (in situ rat gut technique) and in vitro antibacterial activities of twenty fluoroquinolones have been evaluated. A biophysical model that relates the absorption of the compounds with their lipophilicity was fitted. The model considers the absorption process from the intestinal lumen as the sum of two resistances in series: aqueous diffusional barrier and lipoidal membrane. Even if partitioning into the membrane and membrane diffusion are both enhanced for lipophilic compounds, the absorption rate constant is limited by the aqueous diffusion. To estimate the influence of structural modifications on each property and to establish the role of lipophilicity in control…
Effects of Ethanol on Intestinal Absorption of Drugs
The effect of chronic alcohol intake on the intestinal absorption of seven compounds belonging to a homologous series (ciprofloxacin derivatives) was evaluated using an in situ rat gut technique that measures the intrinsic absorption rates of the compounds both in control and chronic alcohol-fed rats. For chronic alcohol treatment, the animals were fed a liquid diet containing ethanol (36% of calories), whereas an isocaloric diet was given to the pair-fed control animals. The biophysical absorption model, relating the intestinal absorption rate constants and partition indexes of the tested compounds, was then established either for control or alcohol-fed animals. Differences were analyzed a…
Harmonization of QSAR Best Practices and Molecular Docking Provides an Efficient Virtual Screening Tool for Discovering New G-Quadruplex Ligands
Telomeres and telomerase are key players in tumorogenesis. Among the various strategies proposed for telomerase inhibition or telomere uncapping, the stabilization of telomeric G-quadruplex (G4) structures is a very promising one. Additionally, G4 stabilizing ligands also act over tumors mediated by the alternative elongation of telomeres. Accordingly, the discovery of novel compounds able to act on telomeres and/or inhibit the telomerase enzyme by stabilizing DNA telomeric G4 structures as well as the development of approaches efficiently prioritizing such compounds constitute active areas of research in computational medicinal chemistry and anticancer drug discovery. In this direction, we…
Targeted delivery of Cyclosporine A by polymeric nanocarriers improves the therapy of inflammatory bowel disease in a relevant mouse model
The therapy of inflammatory bowel diseases is still rather inefficient, and about 80% of patients require surgery at some stage. Improving the treatments by more efficient medication is, therefore, an urgent medical need. The objective of this project was to demonstrate targeted delivery of Cyclosporine-A (CYA) to the inflamed areas of the intestinal mucosa after oral administration, enabling improved alleviation of the symptoms and, at the same time, reduced systemic drug absorption and associated adverse effects. As had already been demonstrated in previous studies, nano- to micrometer-sized drug particles will accumulate at inflamed mucosal areas, providing a platform for such purposes. …
Microneedle-Based Delivery: An Overview of Current Applications and Trends
Microneedle arrays (MNA) are considered as one of the most promising resources to achieve systemic effects by transdermal delivery of drugs. They are designed as a minimally invasive, painless system which can bypass the stratum corneum, overcoming the potential drawbacks of subcutaneous injections and other transdermal delivery systems such as chemical enhancers, nano and microparticles, or physical treatments. As a trendy field in pharmaceutical and biomedical research, its applications are constantly evolving, even though they are based on very well-established techniques. The number of molecules administered by MNA are also increasing, with insulin and vaccines administration being the …
In situ kinetic modelling of intestinal efflux in rats: functional characterization of segmental differences and correlation with in vitro results.
The objective was to devise and apply a novel modelling approach to combine segmental in situ rat perfusion data and in vitro cell culture data, in order to elucidate the contribution of efflux in drug absorption kinetics. The fluoroquinolone CNV97100 was used as a model P-gp substrate. In situ intestinal perfusion was performed in rat duodenum, jejunum, ileum and colon to measure the influence of P-gp expression on efflux. Inhibition studies of CNV97100 were performed in the presence of verapamil, quinidine, cyclosporin A and p-aminohippuric acid. Absorption/efflux parameters were modelled simultaneously, using data from both in situ studies as well as in vitro studies. The maximal efflux …
Guava: phytochemical composition of a potential source of antioxidants for cosmetic and/or dermatological applications
Made available in DSpace on 2018-11-28T14:21:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01. Added 1 bitstream(s) on 2019-10-09T18:26:25Z : No. of bitstreams: 1 S1984-82502017000200612.pdf: 803011 bytes, checksum: 199524e8d40cccb25490594ec61b3ed8 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) PADC-FCF-UNESP Fundação para o Desenvolvimento da UNESP (FUNDUNESP) Guava (Psidium guajava L.) is a native fruit of the American tropics with commercial applications for its taste, flavor and aroma. Numerous pharmacological uses have been described for it, such as the antiseptic effect of it…
Absorption-partition relationships for true homologous series of xenobiotics as a possible approach to study mechanisms of surfactants in absorption. IV. Phenylacetic acid derivatives and anionic surfactants
Abstract This paper — the latest in this series of reports — deals with the effects of the anionic surfactant sodium lauryl sulfate on the colonic absorption of acidic xenobiotics (phenylalkylcarboxylic acids), as compared with those exerted by the nonionic polysorbate 80. The effects of these surfactants are qualitatively identical but quantitatively different. Thus, the increase in polarity of the colonic absorbant membrane is greater with lauryl sulfate, whereas micellar solubilization is much higher with polysorbate. As for the rest (i.e. the elimination of the stagnant aqueous diffusion layer as a limiting step for absorption), the two surfactants behave in a similar way. The biopharma…