ABSTRACT
In this paper, two medusa-like ACyDs, modified at the primary rim bearing four (ACyD4) and eight carbons (ACyD8) acyl chain length, and one bouquet-like CyD, modified at primary side with thiohexyl and at secondary one with oligoethylene moiety (SC6OH), were investigated for their ability to assemble in nanostructures or to form hybrid dipalmitoylphosphatidylcholine (DPPC)/ACyDs systems. The lipophilicity of these molecules and the different preparation methods used in this study (thin layer evaporation and nanoprecipitation method) significantly affect the aggregation behaviour in aqueous medium. Except for the shortest medusa-like ACyD4, the other ACyDs formed stable nanoaggregates for at least 45 days. The effect of ACyDs on the thermotropic behaviour of DPPC liposomes was also studied by differential scanning calorimetry analysis, thus elucidating their interaction with liposomes to afford hybrid liposome/ACyDs systems. The medusa-like ACyD4 cannot be used to realize nanosystems because it quickly aggregates or it induces a complete destabilization of the liposomes. At the highest concentration investigated (0.01 molar fraction), both ACyD8 and SC6OH interacted with DPPC liposomes, forming ACyD/DPPC or SC6OH/DPPC hybrid vesicular carriers.
Subject(s)
1,2-Dipalmitoylphosphatidylcholine/chemistry , Cyclodextrins/chemistry , Drug Carriers/chemistry , Lipid Bilayers/chemistry , Liposomes/chemistry , Nanostructures/chemistry , Calorimetry, Differential Scanning , Chemical Phenomena , Hydrophobic and Hydrophilic Interactions , Magnetic Resonance Spectroscopy , Molecular Structure , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Resumen: Objetivo: El propósito de este estudio fue describir las percepciones de docentes de enfermería de habla hispana en América Latina, sobre las competencias relacionadas a la salud global que deben mostrar los estudiantes de enfermería del pregrado. Métodos: Este estudio descriptivo fue basado en una muestra de docentes de escuelas de enfermería miembros de la Asociación Latinoamericana de Escuelas y Facultades de Enfermería (ALADEFE) y de la Asociación de Escuelas de la Zona Centro Sur de México, las cuales recibieron un correo electrónico con una liga para responder una encuesta electrónica por Survey Monkey©. La encuesta incluyó una lista de 30 competencias en salud global dividida en seis dimensiones. Los docentes indicaron en una escala Likert de 4 puntos la relevancia de cada competencia para la educación de enfermería en el nivel de pregrado (1 = Completamente en desacuerdo; 2 = En desacuerdo; 3 = De acuerdo; 4 = Completamente de acuerdo). Resultados: En total, 110 profesores de nueve países respondieron a la encuesta. El promedio de cada ítem fue entre 3.0 - 4.0, esto indica que los profesores estuvieron de acuerdo en que todas las competencias son relevantes para la formación de estudiantes de enfermería a nivel de pregrado. Conclusiones: Los resultados de este estudio sugirieron que estas competencias deben ser incluidas en los currículos de enfermería a nivel de pregrado, para formar a los estudiantes en su labor como enfermeras y enfermeros en un mundo globalizado y prepararlos para contribuir a la Cobertura y el Acceso Universal a la Salud (Salud Universal).
Abstract: Objective: To describe the perceptions of Spanish-speaking nursing teachers in Latin America on the global health competences which, undergraduate nursing students should demonstrate. Methods: This descriptive study was based on a sample of teachers of nursing schools belonging to the Latin American Association of Nursing Schools and Faculties, and the Association of Schools of the Center-South Zone in Mexico. These institutions received an invitation via e-mail to respond to a survey through the Survey Monkey© platform. The survey included a list of 30 Global Health competencies grouped in 6 dimensions. Teachers indicated through a 4-point Likert scale their perception on the relevance to undergraduate nursing education of each of these competencies (1 = total disagreement, 2 = disagreement, 3 = agreement, 4 = total agreement). Results: In total, 110 professors of 9 countries responded to the survey. The average score per item was 3.0 - 4.0 suggesting that the teachers agreed that all competencies are relevant to the formation of undergraduate nursing students. Conclusions: These results suggested that these competencies should be part of the objectives of undergraduate nursing curricula in order to prepare the students to contribute to the Coverage and Access to Universal Health agenda.
Resumo: Objetivo: O propósito deste estudo foi descrever as percepções de docentes de enfermagem de fala hispana na América Latina, sobre as competências relacionadas à saúde global que devem mostrar os estudantes de enfermagem de graduação. Métodos: Este estudo descritivo foi baseado em uma amostra de docentes de escolas de enfermagem membros da Associação Latino-americana de Escolas e Faculdades de Enfermagem (ALADEFE) e da Associação de Escolas da Zona Centro Sul do México, as quais receberam um e-mail electrónico com um link para responder uma enquete electrónica por Survey Monkey©. A enquete incluiu uma lista de 30 competências em saúde global dividida em seis dimensões. Os docentes indicaram em uma escala Likert de 4 pontos a relevância de cada competência para a educação de enfermagem no nível de graduação (1 = Completamente em discordância; 2 = Em discordância; 3 = Em concordância; 4 = Completamente em concordância). Resultados: Em total, 110 professores de nove países responderam à enquete. A média de cada item foi entre 3.0-4.0, isto indica que os professores concordaram em que todas as competências são relevantes para a formação de estudantes de enfermagem a nível de graduação. Conclusões: Os resultados deste estudo sugeriram que estas competências devem ser incluídas nos currículos de enfermagem a nível de graduação, para formar aos estudantes em seu labor como enfermeiras e enfermeiros em um mundo globalizado e prepará-los para contribuir à Cobertura e o Acesso Universal à Saúde (Saúde Universal).
Subject(s)
Humans , Male , FemaleABSTRACT
ABSTRACT Seeds of Acacia farnesiana are commonly sold in the local markets of northeastern Brazil as a therapeutic agent. The present work aimed to evaluate the anti-inflammatory and analgesic activities of proteins obtained from A. farnesiana seeds. Five different protein fractions (albumin, globulin, prolamin, acidic and basic glutelins) were obtained and investigated for the protein pattern, the presence of hemagglutinating and proteolytic activities. The globulin fraction (GLB) was also evaluated for anti-inflammatory and analgesic activities. Globulins reduced the paw edema induced by carrageenan in a dose-dependent manner, which was accompanied by a reduction of myeloperoxidase activity (p < 0.05). Additionally, GLB reduced the neutrophil peritoneal migration induced by carrageenan. However, GLB was not able to inhibit the edema triggered by dextran. Pre-treatment with globulins reduced the abdominal constrictions induced by acetic acid as well as the paw licking time induced by formalin (69.1% at first phase). However, it did not produce a significant antinociceptive effect in the hot plate test (55-56 °C). Treating the GLB with heat (at 100 °C for 30 min) abolished its anti-edematogenic and hemagglutinating activities. Our results showed that seeds from A. farnesiana are a source of proteins with anti-inflammatory and analgesic properties.
RESUMO Sementes de Acacia farnesiana são comumente vendidas em feiras locais no nordeste do Brasil como agente terapêutico. O presente trabalho objetivou avaliar as atividades antiinflamatória e antinociceptiva de proteínas obtidas de sementes de A. farnesiana. Cinco frações protéicas distintas (albuminas, globulinas, prolaminas, glutelinas ácidas e básicas) foram obtidas e investigadas quanto o perfil de proteínas, presença de atividade hemaglutinante e proteolítica. A fração globulina (GLB) também foi avaliada quanto a presença de atividade antiinflamatória e analgésica. Globulinas reduziram o edema de pata induzido por carragenina de modo dependente da dose que foi acompanhada da redução da atividade da mieloperoxidase (p < 0,05). Em adição, GLB reduziu a migração de neutrófilos para cavidade peritoneal induzida por carragenina. Entretanto, GLB não foi capaz de inibir o edema induzido por dextrana. O pré-tratamento com globulinas reduziu as contorções abdominais induzidas por ácido acético, bem como o tempo de lambedura da pata induzida por formalina (69.1% na primeira fase). Por outro lado, GLB não produziu um efeito antinociceptivo significante no teste de placa quente (55-56 °C). O pré-tratamento de GLB com calor (100 °C por 30 min) aboliu sua atividade anti-edematogênica e hemaglutinante. Nossos resultados mostraram que sementes de A. farnesiana são fonte de proteínas com propriedades antiinflamatórias e analgésicas.
Subject(s)
Acacia/classification , Analgesics/classification , Anti-Inflammatory Agents/classification , Nociception/classification , Lectins/analysisABSTRACT
BACKGROUND: Angola is one of the largest African countries with continuing levels of insecurity, considerable weakness in terms of respect for human rights, destroyed infrastructure and low transparency and social accountability levels. The health system displays gaps and nursing represents the main contingent among human resources in health. AIM: This research aims to understand the healthcare context in Angola from the perspective of Brazilian nurses who were involved in helping their Angolan colleagues. This general view of health services is followed by a description of nursing workforce particularities at a tertiary health service in the province of Luanda. METHODS: Data were extracted from the database of the Global Network of World Health Organization Collaborating Centres for Nursing and Midwifery Development, constructed based on technical visits to Angola in 2009. Information related to health service characteristics was used, focusing on nursing human resource activities at two tertiary, one secondary and one primary health institutions located in the province of Luanda. The study data were analysed through descriptive statistics. FINDINGS: Among the problems the nursing workforce faces, the lack of human, material and financial resources stands out, as well as insufficient professional qualification, excessive work journeys, low remunerations, non-valuation of professionals, leading to unsatisfactory work environments and discouraged human resources. CONCLUSIONS: Nursing in Angola is conquering its professional space. Therefore, regulatory policies are fundamental, defining the rights and obligations of all categories involved, with a view to determining nurses' function in the health team, including respect for and acknowledgement of their role in the community.
Subject(s)
Attitude of Health Personnel , Health Policy , International Cooperation , Nurses/supply & distribution , Angola , Brazil , Demography , Female , Health Services Needs and Demand , Humans , Interviews as Topic , MaleABSTRACT
Chitosan (CH) was used as a biocompatible and bioadhesive polymer material to prepare solid dispersions as well as hydrogels loaded with dexamethasone sodium phosphate (DSP), a steroidal anti-inflammatory agent clinically used for treatment of different mouth diseases. Binary solid dispersions at various drug-to-polymer weight ratios were prepared by freeze-drying; their direct compression gave tablets which were characterized for the swelling behaviour and drug release in vitro. Similarly, DSP-loaded hydrogels composed of CH and glycerine were prepared and characterized. CH and DSP showed a good physical compatibility. A slow and prolonged release of the drug was observed in vitro from both kinds of systems. The swelling properties of the polymer seemed to be the main parameter affecting the drug release profile from both tablets and hydrogels at the pH value of mouth. In vivo buccal application of both the systems allowed to obtain a prolonged release of DSP, as compared with a glycerine solution of the drug. From the in vitro swelling studies and in vivo test, the 2:1 CH-DSP solid dispersion in particular can be designated for further investigation.
Subject(s)
Chitosan/chemistry , Dexamethasone/analogs & derivatives , Drug Delivery Systems , Mouth Mucosa , Calorimetry, Differential Scanning , Dexamethasone/administration & dosage , Humans , HydrogelsABSTRACT
Four different oral lorazepam tablets (Tavor tablets as reference preparation and three generic tablet formulations, A, B and C) were investigated after administration to 12 rabbits to evaluate their bioequivalence. A single 2 mg/kg dose was administered orally as powder and lorazepam plasma concentrations were determined by a validated HPLC method. Maximum plasma concentrations (Cmax), of 207 ng/ml (reference), 198 ng/ml (A), 166 ng/ml (B) and 169 ng/ml (C) were achieved. Lorazepam appeared in the plasma at 0.66 h (Tmax) for all formulations, probably because the disintegration step was bypassed due to the pulverization of the administered doses. Areas under the plasma concentration-time curves (AUC(0-t) and AUC(0-infinity)) were determined. The obtained AUC(0-t) values were 556.57 ng h/ml (reference), 554.70 ng h/ml (A), 493.08 ng h/ml (B), and 487.88 ng h/ml (C). ANOVA results (P > or = 0.05) and 90% confidence intervals for the mean ratio (T/R) of AUC(0-t), AUC(0-infinity), and Cmax were within the EMEA acceptance range. Pharmacokinetic and statistical results of this study show that the four tested drug products (Tavor, A, B, C) are to be considered bioequivalent and interchangeable in medical practice.
Subject(s)
Hypnotics and Sedatives/administration & dosage , Lorazepam/administration & dosage , Animals , Area Under Curve , Chemistry, Pharmaceutical , Female , Rabbits , Solubility , Tablets , Therapeutic EquivalencyABSTRACT
The preparation and technological characterization of nanosphere formulations (NS) containing the anticancer drug paclitaxel (PTX) are reported. Poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) nanospheres (NS) were prepared by a solvent displacement method. They showed a mean particle size in the range 150-300 nm, with a high homogeneity (polydispersity index < 0.3). For long term stability, NS require additional procedures, such as freeze-drying. In this study, the effect on NS particle size and surface charge of different lyoprotectants (mono- and disaccharides, polyalcohols, and hydroxypropyl-beta-cyclodextrin) at various concentrations was tested by means of light scattering size analysis. The formulations freeze-dried with the addition of 10% glucose (w/v) showed interesting characteristics after freeze-drying. They were chosen for specific studies on drug encapsulation efficiency, in vitro drug release and biological activity on the human anaplastic thyroid carcinoma cell line 8305C. The PLGA NS, in particular, showed a cell growth inhibitory activity comparable to the free drug.
Subject(s)
Cryoprotective Agents/chemistry , Delayed-Action Preparations/chemistry , Freeze Drying/methods , Nanotubes/chemistry , Paclitaxel/administration & dosage , Paclitaxel/pharmacokinetics , Thyroid Neoplasms/metabolism , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Cell Line, Tumor , Chemistry, Pharmaceutical/methods , Crystallization/methods , Diffusion , Humans , Materials Testing , Metabolic Clearance Rate , Nanotubes/ultrastructure , Paclitaxel/chemistry , Particle SizeABSTRACT
This study investigates the potentiality of nanosphere colloidal suspensions as sustained release systems for intravenous administration of docetaxel (DTX). Nanospheres were prepared by solvent displacement method using polylactic acids (PLA) at different molecular weight and polylactic-co-glycolic (PLGA) as biodegradable matrices. The systems were characterized by light scattering analysis for their mean size, size distribution and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The average diameters of the nanoparticles ranged from 100 to 200 nm. Negative zeta potential values were observed for all systems, particularly the nanospheres produced with the lowest molecular weight PLA showed a zeta potential value of -28mV. Differential scanning calorimetry analysis (DSC) suggested that DTX was molecularly dispersed in the polymeric matrices. A biphasic release of DTX was observed for all colloidal suspensions, after a burst effect in which about 50% (w/w) of the loaded drug was released a sustained release profile for about 10 days was observed. To evaluate the influence of the polymeric carrier on the interaction of DTX with biological membranes, we performed an in vitro study using lipid vesicles made of dipalmitoylphosphatidylcholine (DPPC) as a biomembrane model. DSC was used as a simple and not invasive technique of analysis. DTX produced a depression of DPPC pretransition peak, no variation of the main phase transition temperature and a significative increase of DeltaH value, showing a superficial penetration of the drug into DPPC bilayer. Kinetic experiments demonstrated that the release process of DTX form nanospheres is affected by the molecular weight of the employed polymers.
Subject(s)
Delayed-Action Preparations/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Polymers/chemistry , Taxoids/chemistry , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacokinetics , Calorimetry, Differential Scanning/methods , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/pharmacokinetics , Diffusion , Docetaxel , Drug Compounding , Injections, Intravenous , Lipid Bilayers/metabolism , Liposomes/chemistry , Microscopy, Electron, Scanning/methods , Molecular Weight , Nanoparticles/ultrastructure , Nanotechnology/methods , Polylactic Acid-Polyglycolic Acid Copolymer , Static Electricity , Surface Properties , Taxoids/administration & dosage , Taxoids/pharmacokinetics , Time FactorsABSTRACT
We evaluated the ability of two modified cyclodextrins, hydroxypropyl-beta-cyclodextrin (HP-beta-Cyd) and 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-Cyd), to influence the percutaneous absorption through isolated human stratum corneum and epidermis (SCE) of celecoxib (CCB). Previous studies demonstrated that DM-beta-Cyd includes the drug, producing a significant increase of water solubility (0.5 mg/ml at 25 degrees C) and dissolution rate of CCB. In this work chemical-physical characterization studies were performed to evaluate the ability of HP-beta-Cyd to include CCB. We showed that only an external interaction could exist between CCB and HP-beta-Cyd that positively influences the water solubility of the drug (0.12 mg/ml at 25 degrees C for CCB-HP-beta-CyD system and 4.12 x 10(-3) mg/ml at 25 degrees C for free CCB). In vitro percutaneous experiments were performed using samples in solution and in suspension containing different Cyd concentrations. Both HP-beta-Cyd and DM-beta-Cyd enhanced drug flux through SCE by means of an increase of dissolution rate of the drug as well as a direct action on the stratum corneum (SC). Histological analysis of treated SCE showed a protective effect of the two Cyds towards an invasive action shown by CCB on SC.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Pyrazoles/pharmacokinetics , Skin Absorption/drug effects , Sulfonamides/pharmacokinetics , beta-Cyclodextrins/pharmacology , 2-Hydroxypropyl-beta-cyclodextrin , Adult , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Calorimetry, Differential Scanning , Celecoxib , Chromatography, High Pressure Liquid , Circular Dichroism , Female , Humans , In Vitro Techniques , Magnetic Resonance Spectroscopy , Permeability , Pyrazoles/chemistry , Skin/drug effects , Skin/metabolism , Solubility , Sulfonamides/chemistry , beta-Cyclodextrins/chemistryABSTRACT
Biphenylylacetic acid (BPAA) was linked to the free hydroxyl group of 2,6-di-O-methyl-beta-Cyclodextrin (DM-beta-CyD) through an ester linkage to obtain the site specific release of the drug to the colon. The conjugate at 1:1 mole ratio was separated from the reaction mixture by semipreparative reverse-phase HPLC and characterized by 1H-NMR, 13C-NMR, IR spectroscopy, mass spectrometry and elemental analysis. Chemico-physical characteristics, such as water solubility and dissolution rate, were evaluated comparatively to the BPAA-DM-beta-CyD inclusion complex. Hydrolysis rates were investigated in media simulating gastro-intestinal fluids and at pH 7.4 in the presence of porcine liver esterase. A rapid release of the drug was observed at acid pH value. In all cases a first order kinetic was observed, characterized by t1/2 value of 1.19, 19 and 4 h for chemical hydrolysis at pH 1.1, at pH 7.4 and enzymatic hydrolysis, respectively. In vitro permeation studies through caco-2 cells confirmed the ability of DM-beta-CyD to increase the absorption of included BPAA. A slow permeation was observed for the drug conjugate to DM-beta-CyD due to the slow release of BPAA.
Subject(s)
Cyclodextrins/chemical synthesis , Cyclodextrins/pharmacokinetics , Phenylacetates/chemical synthesis , Phenylacetates/pharmacokinetics , beta-Cyclodextrins , Caco-2 Cells , Drug Evaluation, Preclinical/methods , Humans , SolubilityABSTRACT
The effects of different concentrations of beta-cyclodextrin (beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CyD) on percutaneous absorption of papaverine hydrochloride (PAP) were investigated. Abdominal rat skin mounted in Franz cells was used for in vitro experiments. To evaluate CyD interaction with a bilayer structure model, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and DPPC-Chol (8:2 mole ratio) vesicles were used. CyD vesicle interaction was evaluated by differential scanning calorimetry. Permeation through rat skin and calorimetric experiments demonstrated that at low concentrations DM-beta-CyD shows higher enhancer activity as a possible result of a perturbing action on the skin by a complexation of its lipid components, but at higher concentrations HP-beta-CyD is the most effective. By considering that HP-beta-CyD presents a very moderate destabilizing action on the skin, we conclude that a 10% aqueous solution of this macrocycle appears to be the most suitable transdermal absorption enhancer for PAP.
Subject(s)
Cyclodextrins/pharmacokinetics , Models, Biological , Skin Absorption/physiology , Abdomen , Administration, Cutaneous , Animals , Circular Dichroism , Cyclodextrins/administration & dosage , Cyclodextrins/chemistry , Dialysis , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , In Vitro Techniques , Male , Membranes, Artificial , Papaverine/administration & dosage , Papaverine/chemistry , Papaverine/pharmacokinetics , Permeability/drug effects , Rats , Vasodilator Agents/administration & dosage , Vasodilator Agents/chemistry , Vasodilator Agents/pharmacokineticsABSTRACT
Poly-D,L-lactide (PDLLA) and polylactide-co-glycolide (PLGA) microspheres containing thymopentin have been prepared by a water-in-oil-in-water-emulsion/solvent evaporation technique. The goal is to stabilize the active compound thymopentin, and to prolong its therapeutic activity, by embedding the drug in a polymeric matrix. The microspheres obtained have been characterized for their morphology and drug content. In-vitro dissolution tests have been performed on the microspheres. Results show that the type of polymer employed (PDLLA or PLGA) does not seem to affect microsphere morphology, while in-vitro dissolution profiles are greatly influenced by the composition of polymer matrix. Ex-vivo evaluation of PLGA microspheres performed on mouse thymocites shows that biological activity of Thymopentin is maintained after loading into PLGA microspheres.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Lactic Acid , Polyglycolic Acid , Thymopentin/administration & dosage , Calorimetry, Differential Scanning , Capsules , Drug Compounding , Emulsions , Lymphocyte Activation/drug effects , Polyesters , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers , Solubility , T-Lymphocytes/drug effectsABSTRACT
Gastric tolerability, absorption and pharmacological activity of the non-steroidal anti-inflammatory drug 4-biphenylacetic acid (BPAA), as an inclusion complex with beta-cyclodextrin (beta-CyD) or chemically modified beta-CyDs: 2,6-di-O-methyl-beta-CyD (DM-beta-CyD), 2,3,6-tri-O-methyl-beta-CyD (TM-beta-CyD) and 2-hydroxypropyl-beta-CyD (HP-beta-CyD), were investigated in the rat after oral administration. BPAA absorption, determined from area under the plasma concentration-time curve (AUC), was increased by complexation with all beta-CyDs in the following order: DM-beta-CyD > TM-beta-CyD > HP-beta-CyD > beta-CyD. The carrageenan paw oedema test demonstrated a significant increase in anti-inflammatory activity of BPAA and the ED50 values, compared with BPAA alone, were reduced to about a third for the BPAA-DM-beta-CyD complex and halved for the others. BPAA complexed with DM-beta-CyD, HP-beta-CyD or beta-CyD showed better gastric tolerability compared with uncomplexed drug, whereas the BPAA-TM-beta-CyD complex produced marked gastric lesions similar in extent to BPAA alone. TM-beta-CyD (500 mg kg-1) and DM-beta-CyD (1000 mg kg-1) caused gastric erosions 21 h after oral administration. The pharmacokinetic profiles of BPAA-beta-CyD complexes have shown that DM-beta-CyD is the most effective in enhancing the bioavailability of BPAA.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Cyclodextrins/chemistry , Drug Delivery Systems/standards , Phenylacetates/pharmacokinetics , beta-Cyclodextrins , Absorption , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Biological Availability , Chromatography, High Pressure Liquid , Cyclodextrins/metabolism , Delayed-Action Preparations , Linear Models , Male , Phenylacetates/administration & dosage , Phenylacetates/adverse effects , Rats , Rats, Sprague-Dawley , Stomach Ulcer/chemically induced , Structure-Activity RelationshipABSTRACT
In this paper we report the investigation of the potential of liposomes as drug carrier for citicoline (1; CDP-choline). The aim of our work is to improve the pharmacokinetic and pharmacodynamic parameters of the drug to facilitate the overcoming of the blood-brain barrier. The thermotropic behaviour of hydrated dispersions of various phospholipids and their mixtures containing 1 have been investigated by differential scanning calorimetry (DSC) to have a clear view of the interaction between the drug and the liposome phospholipids. By the values of transition peak temperature (Tm) and transition enthalpy (delta H) we note a strong interaction between 1 and the polar heads of L-alpha-dipalmitoylphosphatidic acid (DPPA) and L-alpha-dipalmitoylphosphatidylserine (DPPS), whereas there is not any considerable interaction between the drug and L-alpha-dipalmitoylphosphatidylcholine (DPPC) or L-alpha-dimyristoylphosphatidylcholine (DMPC); in any case no interaction occurs between 1 and the hydrophobic part of the phospholipid. So we conclude that all the drug is fitted into the aqueous spaces. The results of the encapsulation efficiency experiments demonstrate how the encapsulation capacity increase with using charged phospholipids, reaching the top with DPPA. Moreover, it was noted that the presence of Cholesterol (Chol) enhances the encapsulation capacity (EC) and drug content (DC) values of DPPC, a neutral phospholipid. The size of the liposomes was determined by light scattering (LS).
Subject(s)
Cytidine Diphosphate Choline/administration & dosage , Drug Carriers , Liposomes , Calorimetry, Differential Scanning , Capsules , Chemistry, Pharmaceutical , Cytidine Diphosphate Choline/chemistry , Drug Compounding , Particle Size , Spectrophotometry, UltravioletABSTRACT
4-Biphenylacetic acid, a potent non-steroidal anti-inflammatory agent forms a solid inclusion complex with beta-cyclodextrin in a 1:1 molar ratio, which exhibits better solubility and dissolution characteristics than the uncomplexed drug. Following oral administration of the complex to rats, quicker and higher drug plasma concentrations can be achieved than with the drug alone. Parallel studies, using the carrageenan paw oedema test, demonstrate a greater anti-inflammatory activity of the complex (ED50 of 2.9 mg kg-1 for the complex and of 6.2 mg kg-1 for the free drug). The complex displayed a better gastric tolerability in the rat than drug alone.
