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1.
Trials ; 23(1): 628, 2022 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-35922823

RESUMEN

BACKGROUND: Women with stress urinary incontinence (SUI) experience urine leakage with physical activity. Currently, the interventional treatments for SUI are surgical, or endoscopic bulking injection(s). However, these procedures are not always successful, and symptoms can persist or come back after treatment, categorised as recurrent SUI. There are longstanding symptoms and distress associated with a failed primary treatment, and currently, there is no consensus on how best to treat women with recurrent, or persistent, SUI. METHODS: A two-arm trial, set in at least 20 National Health Service (NHS) urology and urogynaecology referral units in the UK, randomising 250 adult women with recurrent or persistent SUI 1:1 to receive either an endoscopic intervention (endoscopic bulking injections) or a standard NHS surgical intervention, currently colposuspension, autologous fascial sling or artificial urinary sphincter. The aim of the trial is to determine whether surgical treatment is superior to endoscopic bulking injections in terms of symptom severity at 1 year after randomisation. This primary outcome will be measured using the patient-reported International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF). Secondary outcomes include assessment of longer-term clinical impact, improvement of symptoms, safety, operative assessments, sexual function, cost-effectiveness and an evaluation of patients' and clinicians' views and experiences of the interventions. DISCUSSION: There is a lack of high-quality, randomised, scientific evidence for which treatment is best for women presenting with recurrent SUI. The PURSUIT study will benefit healthcare professionals and patients and provide robust evidence to guide further treatment and improve symptoms and quality of life for women with this condition. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) registry ISRCTN12201059. Registered on 09 January 2020.


Asunto(s)
Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Esfínter Urinario Artificial , Adulto , Femenino , Humanos , Calidad de Vida , Medicina Estatal , Resultado del Tratamiento , Incontinencia Urinaria/diagnóstico , Incontinencia Urinaria/cirugía , Incontinencia Urinaria de Esfuerzo/diagnóstico , Incontinencia Urinaria de Esfuerzo/cirugía
2.
Biorheology ; 57(2-4): 77-85, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33459690

RESUMEN

BACKGROUND: Foam sclerotherapy is the process of using an aqueous foam to deliver surfactant to a varicose vein to damage vein wall endothelial cells, causing the vein to spasm, collapse and ultimately be re-absorbed into the body. Aqueous foams are complex fluids that can exhibit a significant yield stress and high effective viscosity which depend on their composition, particularly the bubble size and liquid fraction. OBJECTIVE: To characterise the properties of foams used for varicose vein sclerotherapy and determine their effectiveness in the displacement of blood during sclerotherapy. METHODS: Foams are modelled as yield stress fluids and their flow profiles in a model vein are predicted. Values of the yield stress are determined from experimental data for three different foams using the Sauter mean of the bubble size distribution. Along with the measured liquid fraction of the foams, this information is collected into a Bingham number which entirely characterises the process of sclerotherapy. RESULTS: Polydispersity in bubble size has a strong effect on the yield stress of a foam and the Sauter mean of the size distribution better captures the effects of a few large bubbles. Reducing the polydispersity increases the yield stress, and a higher yield stress results in a larger plug region moving along the vein, which is more effective in displacing blood. The width of the plug region is proportional to the Bingham number, which also has a quadratic dependence on the liquid fraction of the foam. Assuming typical values for the rate of injection of a foam, we predict that for a vein of diameter 5 mm, the most effective foams have low liquid fraction, a narrow size distribution, and a Bingham number B ≈ 4.5. CONCLUSIONS: The Sauter mean radius provides the most appropriate measure of the bubble size for sclerotherapy and the Bingham number then provides a simple measure of the efficacy of foam sclerotherapy in a vein of a given size, and explains the ability of different foams to remove varicose veins. Foams containing small bubbles, with a narrow size distribution, and a low liquid fraction are beneficial for sclerotherapy.


Asunto(s)
Escleroterapia , Várices , Células Endoteliales , Humanos , Polidocanol , Polietilenglicoles , Soluciones Esclerosantes/uso terapéutico , Várices/tratamiento farmacológico
3.
Obes Rev ; 17(3): 225-34, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26775902

RESUMEN

Guidelines suggest that very-low-energy diets (VLEDs) should be used to treat obesity only when rapid weight loss is clinically indicated because of concerns about rapid weight regain. Literature databases were searched from inception to November 2014. Randomized trials were included where the intervention included a VLED and the comparator was no intervention or an intervention that could be given in a general medical setting in adults that were overweight. Two reviewers characterized the population, intervention, control groups, outcomes and appraised quality. The primary outcome was weight change at 12 months from baseline. Compared with a behavioural programme alone, VLEDs combined with a behavioural programme achieved -3.9 kg [95% confidence interval (CI) -6.7 to -1.1] at 1 year. The difference at 24 months was -1.4 kg (95%CI -2.6 to -0.2) and at 38-60 months was -1.3 kg (95%CI -2.9 to 0.2). Nineteen per cent of the VLED group discontinued treatment prematurely compared with 20% of the comparator groups, relative risk 0.96 (0.56 to 1.66). One serious adverse event, hospitalization with cholecystitis, was reported in the VLED group and none in the comparator group. Very-low-energy diets with behavioural programmes achieve greater long-term weight loss than behavioural programmes alone, appear tolerable and lead to few adverse events suggesting they could be more widely used than current guidelines suggest.


Asunto(s)
Restricción Calórica , Obesidad/dietoterapia , Pérdida de Peso , Glucemia/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Bases de Datos Factuales , Dieta Reductora , Ayuno , Humanos , Insulina/sangre , Ensayos Clínicos Controlados Aleatorios como Asunto , Sensibilidad y Especificidad , Resultado del Tratamiento
4.
Trials ; 16: 567, 2015 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-26651344

RESUMEN

BACKGROUND: Lower urinary tract symptoms (LUTS) comprise storage symptoms, voiding symptoms and post-voiding symptoms. Prevalence and severity of LUTS increase with age and the progressive increase in the aged population group has emphasised the importance to our society of appropriate and effective management of male LUTS. Identification of causal mechanisms is needed to optimise treatment and uroflowmetry is the simplest non-invasive test of voiding function. Invasive urodynamics can evaluate storage function and voiding function; however, there is currently insufficient evidence to support urodynamics becoming part of routine practice in the clinical evaluation of male LUTS. DESIGN: A 2-arm trial, set in urology departments of at least 26 National Health Service (NHS) hospitals in the United Kingdom (UK), randomising men with bothersome LUTS for whom surgeons would consider offering surgery, between a care pathway based on urodynamic tests with invasive multichannel cystometry and a care pathway based on non-invasive routine tests. The aim of the trial is to determine whether a care pathway not including invasive urodynamics is no worse for men in terms of symptom outcome than one in which it is included, at 18 months after randomisation. This primary clinical outcome will be measured with the International Prostate Symptom Score (IPSS). We will also establish whether inclusion of invasive urodynamics reduces rates of bladder outlet surgery as a main secondary outcome. DISCUSSION: The general population has an increased life-expectancy and, as men get older, their prostates enlarge and potentially cause benign prostatic obstruction (BPO) which often requires surgery. Furthermore, voiding symptoms become increasingly prevalent, some of which may not be due to BPO. Therefore, as the population ages, more operations will be considered to relieve BPO, some of which may not actually be appropriate. Hence, there is sustained interest in the diagnostic pathway and this trial could improve the chances of an accurate diagnosis and reduce overall numbers of surgical interventions for BPO in the NHS. The morbidity, and therapy costs, of testing must be weighed against the cost saving of surgery reduction. TRIAL REGISTRATION: Controlled-trials.com - ISRCTN56164274 (confirmed registration: 8 April 2014).


Asunto(s)
Síntomas del Sistema Urinario Inferior/diagnóstico , Hiperplasia Prostática/diagnóstico , Obstrucción del Cuello de la Vejiga Urinaria/diagnóstico , Urodinámica , Protocolos Clínicos , Diagnóstico Diferencial , Humanos , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/fisiopatología , Síntomas del Sistema Urinario Inferior/cirugía , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Prostatectomía , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/fisiopatología , Hiperplasia Prostática/cirugía , Proyectos de Investigación , Encuestas y Cuestionarios , Factores de Tiempo , Reino Unido , Procedimientos Innecesarios , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Obstrucción del Cuello de la Vejiga Urinaria/fisiopatología , Obstrucción del Cuello de la Vejiga Urinaria/cirugía
5.
Biomater Sci ; 3(12): 1539-44, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26347909

RESUMEN

With the aid of stimulus-responsive hydrogel substrates composed of ABA triblock copolymer micelles, we monitored the morphological dynamics of myoblast (C2C12) cells in response to an abrupt change in the substrate elasticity by live cell imaging. The remodeling of actin cytoskeletons could be monitored by means of transient transfection with LifeAct-GFP. Dynamic changes in the orientational order of actin filaments were characterized by an order parameter, which enables one to generalize the mechanically induced actin cytoskeletons as a break of symmetry. The critical role that acto-myosin complexes play in the morphological transition was verified by the treatment of cells with myosin II inhibitor (blebbistatin) and the fluorescence localization of focal adhesion contacts. Such dynamically tunable hydrogels can be utilized as in vitro cellular micro-environments that can exert time-dependent stimuli to mechanically regulate target cells.


Asunto(s)
Citoesqueleto de Actina/química , Mioblastos/química , Miosina Tipo II/química , Citoesqueleto de Actina/metabolismo , Adhesión Celular , Línea Celular , Rastreo Celular , Elasticidad , Mioblastos/citología , Miosina Tipo II/metabolismo , Imagen Óptica , Transfección
6.
BMC Obes ; 2: 35, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26401345

RESUMEN

BACKGROUND: Regular weighing in pregnant women is not currently recommended in many countries but has been suggested to prevent excessive gestational weight gain. This study aimed to establish the feasibility and acceptability of incorporating regular weighing, setting maximum weight gain targets and feedback by community midwives. METHODS: Low risk pregnant women cared for by eight community midwives were randomised to usual care or usual care plus the intervention at 10-14 weeks of pregnancy. The intervention involved community midwives weighing and plotting weight on a weight gain chart, setting weight gain limit targets, giving brief feedback at each antenatal appointment and encouraging women to weigh themselves weekly between antenatal appointments. Women and midwives were interviewed about their views of the intervention. The focus of the study was on process evaluation. RESULTS: Community midwives referred 123 women and 115 were scheduled for their dating scan within the study period. Of these, 84/115 were approached at their dating scan and 76/84 (90.5 %) randomised. Data showed a modest difference favouring the intervention group in the percentage of women gaining excessive gestational weight (23.5 % versus 29.4 %). The intervention group consistently reported smaller increases in depression and anxiety scores throughout pregnancy compared with usual care. Most women commented the intervention was useful in encouraging them to think about their weight and believed it should be part of routine antenatal care. Community midwives felt the intervention could be implemented within routine care without adding substantially to consultation length, thus not perceived as adding substantially to their workload. CONCLUSIONS: The intervention was feasible and acceptable to pregnant women and community midwives and was readily implemented in routine care. TRIAL REGISTRATION: ISRCTN81605162.

7.
BMC Obes ; 3: 7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26885375

RESUMEN

BACKGROUND: Many pregnant women gain excess weight during pregnancy which increases the health risks to the mother and her baby. Interventions to prevent excess weight gain need to be given to the whole population to prevent excess weight gain. The aim of this study was to assess the effectiveness of a simple and brief intervention embedded withinroutine antenatal care to prevent excessive gestation weight gain. METHODS: Six hundred and ten pregnant women (between 10-14 weeks gestation), aged ≥18 years with a body mass index (BMI) ≥18.5 kg/m2, planned to receive community midwife led care or shared care at the time of recruitment are eligible to take part in the study. Women will be recruited from four maternity centres in England. Community midwives complete a short training module before delivering the intervention. In the intervention, midwives weigh women, set maximum weight limits for weight gain at each antenatal appointment and ask women to monitor their weight at home. Themaximum weight limit is adjusted by the midwife at each antenatal appointment if women have exceeded their maximum weight gain limit set at their previous appointment. The intervention will be compared with usual antenatal care. The primary outcome is the proportion of women per group who exceed the Institute of Medicine guidelines for gestational weight gain at 38 weeks of pregnancy according to their early pregnancy BMI category. DISCUSSION: The proposed trial will test a brief intervention comprising regular weighing, target setting and monitoring ofweight during pregnancy that can be delivered at scale as part of routine antenatal care. Using the professional expertise of community midwives, but without specialist training in weight management, the intervention will incur minimal additionalhealthcare costs, and if effective at reducing excess weight gain, is likely to be very cost effective. TRIAL REGISTRATION: Current controlled trials ISRCTN67427351. Date assigned 29/10/2014.

8.
Pharm Res ; 29(9): 2543-54, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22638869

RESUMEN

PURPOSE: CriticalSorb™ is a novel absorption enhancer based on Solutol(®) HS15, one that has been found to enhance the nasal transport. It is in clinical trials for nasal delivery of human growth hormone. The hypothesis was that permeating enhancement effects of the Solutol(®)HS15 component would translate to the intestine. METHODS: Rat colonic mucosae were mounted in Ussing chambers and Papp values of [(14)C]-mannitol, [(14)C]-antipyrine, FITC-dextran 4000 (FD-4), and TEER values were calculated in the presence of CriticalSorb™. Tissues were fixed for H & E staining. Caco-2 monolayers were grown on Transwells™ for similar experiments. RESULTS: CriticalSorb™(0.01% v/v) significantly increased the Papp of [(14)C]-mannitol, FD-4 [(14)C]-antipyrine across ileal and colonic mucosae, accompanied by a decrease in TEER. In Caco-2 monolayers, it also increased the Papp of [(14)C]-mannitol FD-4 and [(14)C]-antipyrine over 120 min. In both monolayers and tissues, it acted as a moderately effective P-glycoprotein inhibitor. There was no evidence of cytotoxicity in Caco-2 at concentrations of 0.01% for up to 24 h and histology of tissues showed intact epithelia at 120 min. CONCLUSIONS: Solutol(®) HS15 is the key component in CriticalSorb™ that enables non-cytotoxic in vitro intestinal permeation and its mechanism of action is a combination of increased paracellular and transcellular flux.


Asunto(s)
Mucosa Intestinal/metabolismo , Animales , Células CACO-2 , Humanos , Masculino , Ratas , Ratas Wistar
9.
Clin Transl Oncol ; 13(10): 742-6, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21975337

RESUMEN

OBJECTIVE Previous research in a rat glioma model has shown that the local intratumoral application of polymerbased drug-eluting beads (DEBs) loaded with doxorubicin or irinotecan suppress tumour growth and prolong survival. For translation into a clinical setting, the present experiment investigates in the healthy cat brain the local and systemic toxicity of a multiple injection shot technique. METHODS Three injection shots were placed, each at a 1 cm distance in the frontal lobe. The DEBs were suspended in an aqueous alginate excipient solution, which becomes subject to a sol-gel transition when injected into the Ca(2+)- rich brain tissue environment. Systemic and local side effects were monitored over a period of two weeks. Injection sites were histologically investigated. RESULTS Gelling of the alginate results in the permanent immobilisation of the microspheres at the implantation site. A distinct local cytotoxic effect of doxorubicin was found with intracerebral and intraventricular haemorrhages, and signs of brain tissue necrosis. In cats injected with irinotecan DEBs, such local adverse side effects did not occur. No signs of systemic toxicity were found with both chemotherapeutics. DISCUSSION We conclude that the multiple injection shot technique with irinotecan DEBs meets feasibility criteria and safety requirements for a clinical application.


Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Camptotecina/análogos & derivados , Doxorrubicina/uso terapéutico , Glioma/tratamiento farmacológico , Microesferas , Animales , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Camptotecina/uso terapéutico , Gatos , Femenino , Glioma/patología , Bombas de Infusión Implantables , Inyecciones Intraventriculares , Irinotecán , Masculino , Necrosis , Seguridad , Resultado del Tratamiento
10.
Int J Pharm ; 413(1-2): 147-54, 2011 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-21554938

RESUMEN

Single shot vaccines of tetanus toxoid (TT) were manufactured using the NanoMix process - a low temperature solvent free encapsulation technology using supercritical fluids. The formulations were injected into mice, and compared to multiple injections of a commercially available alum adsorbed TT vaccine. After 5 months the antibody titres were found to be similar for both the alum adsorbed and microparticle formulations, demonstrating for the first time the potential of formulating antigens in PLA microparticles using the supercritical fluid (NanoMix) technique to produce single shot vaccines. The results are likely to be due to the maintenance of toxoid bioactivity and some degree of sustained release of the encapsulated antigens, resulting in repeated stimulation of antigen presenting cells eliminating the need for multiple immunisations. This demonstrates the potential of this supercritical fluid processing technique to reduce the need for booster doses in a vaccine regimen.


Asunto(s)
Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Toxoide Tetánico/administración & dosificación , Toxoide Tetánico/química , Adyuvantes Inmunológicos/administración & dosificación , Compuestos de Alumbre , Animales , Grupos Control , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Portadores de Fármacos , Femenino , Inmunización , Ácido Láctico/química , Ratones , Ratones Endogámicos BALB C , Tamaño de la Partícula , Placebos , Poliésteres , Polímeros/química , Tétanos/inmunología , Toxoide Tetánico/inmunología , Vacunas/administración & dosificación , Vacunas/química , Vacunas/inmunología
11.
J Drug Target ; 17(7): 512-23, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19534582

RESUMEN

Folic acid has been investigated as a targeting ligand for imaging and therapeutic agent for over a decade; however, studies on its use in targeting of nonviral gene or nucleic acids delivery systems are sparse. This study assesses potential application of a new folic acid conjugate with aminomethacrylate-phosphoryl-choline based copolymer (DMAEMA-MPC-FA) as a targeting gene delivery vector. The folate-conjugated polymers produce colloidally stable polyplexes with a particle size <200 nm and demonstrate the ability to protect DNA from enzymatic degradation to a certain extent. In cells that overexpress folate receptors (MCF-7 and KB cultures), the conjugated systems show a folate-specific association and achieved significantly enhanced transfection efficiency, compared to the nonconjugated control, with a dramatically reduced nonspecific cellular association. The transfection enhancement is achieved without a corresponding increase in cellular association, suggesting that an internal cellular trafficking of folate-conjugated system may be altered, resulting in an increased transfection efficacy. In summary, a new folate-conjugated aminomethacrylate-phosphorylcholine copolymer is capable of forming colloidal complexes with DNA, modulating their specific cell uptake and improving the level of cell transfection in folate expressing cells.


Asunto(s)
Proteínas Portadoras/metabolismo , ADN/administración & dosificación , Ácido Fólico/administración & dosificación , Técnicas de Transferencia de Gen , Receptores de Superficie Celular/metabolismo , Cationes , Línea Celular Tumoral , Coloides , Receptores de Folato Anclados a GPI , Ácido Fólico/química , Vectores Genéticos , Humanos , Células KB , Ligandos , Metacrilatos/química , Tamaño de la Partícula , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Polímeros/química , Transfección/métodos
12.
Med Device Technol ; 19(2): 42, 44-5, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18605292

RESUMEN

This two-part article considers the complexities of developing and commercialising combination products using examples from experience with drug-eluting stents and drug-eluting beads. Part I discusses the technical challenges of developing these products.


Asunto(s)
Sistemas de Liberación de Medicamentos , Equipos y Suministros , Materiales Biocompatibles , Stents Liberadores de Fármacos , Humanos
13.
J Phys Chem B ; 112(32): 9652-9, 2008 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-18637682

RESUMEN

We have characterized three diblock copolymers bearing zwitterionic phosphorylcholine and weak tertiary amine groups, namely, poly[((2-(methacryloyloxy)ethyl)phosphorylcholine)30- block-(2-(dimethylamino)ethyl methacrylate)60] (denoted as MPC30-DMA60, Mn=18,000), poly[((2-(methacryloyloxy)ethyl)phosphorylcholine)30- block-(2-(diethylamino)ethyl methacrylate)60) (denoted as MPC30-DEA60, Mn=20,000), and poly[((2-(methacryloyloxy)ethyl)phosphorylcholine)30- block-(2-(diisopropylamino)ethyl methacrylate)60) (denoted as MPC30-DPA60, Mn=21,000), by studying their surface tension and solution aggregation through a combined approach of surface tension measurement, dynamic light scattering, and small-angle neutron scattering. Our results show that larger tertiary amine substituents lead to an increasing tendency to form micellar aggregates, which is consistent with the increasing copolymer hydrophobicity. Thus, MPC30-DMA60 did not aggregate under the experimental conditions studied. The free chains exist in the form of thin cylinders, whose length decreases with copolymer concentration and solution temperature but increases with solution pH. The diameters of the MPC30-DMA60 cylinders remained almost constant at around 30 A under all the conditions studied. At the lower copolymer concentration of 0.5 wt %, the cylindrical lengths correspond to the persistence length of the copolymer backbone and are close to its full length, indicating a rather high rigidity. Further data analysis showed that, at the two higher concentrations of 2 and 4 wt %, the phosphorylcholine and amine blocks associate, inducing bending of the copolymer backbone. One backbone kink was required to satisfy all the constraints, including the dry volume of the copolymer. MPC30-DEA60 showed a similar trend of pH- and concentration-dependent conformational responses for the free copolymer, but in addition micellar aggregation occurred at pH 9. In contrast, MPC30-DPA60 exhibited significantly reduced solubility associated with strong aggregation, which is consistent with it being the most hydrophobic copolymer in the series.


Asunto(s)
Concentración de Iones de Hidrógeno , Fosforilcolina/química , Polímeros/química , Nanotecnología
15.
Langmuir ; 22(26): 10989-93, 2006 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-17154575

RESUMEN

A well-defined, double-hydrophilic diblock copolymer comprising poly[2-(methacryloyloxy)ethyl phosphorylcholine]-block-(glycerol monomethacrylate) (PMPC30-PGMA30, where the numbers represent the average degrees of polymerization for each block) was evaluated for the synthesis of colloidally stable ultrafine magnetite sols. Sterically stabilized paramagnetic sols were prepared in aqueous solution by chemical coprecipitation of ferric and ferrous salts in the presence of this block copolymer. The PMPC30-PGMA30-stabilized magnetite sol had a mean transmission electron microscopy (TEM) diameter of 9.4 +/- 1.7 nm and a mean hydrodynamic diameter of 34 nm. This sol exhibited improved colloidal stability with respect to long-term storage and pH variation compared with magnetite sols prepared in the presence of alternative water-soluble homopolymers and diblock copolymers. Fourier transform infrared (FT-IR) spectroscopy, thermogravimetry, electron spectroscopy imaging (ESI), and zeta potential studies indicate that the PMPC30-PGMA30 diblock copolymer was adsorbed onto the surface of the sol via the PGMA30 block, with the PMPC30 chains acting as the stabilizing block. Such sterically stabilized sols are expected to be improved contrast agents for magnetic resonance imaging (MRI) applications.


Asunto(s)
Materiales Biocompatibles Revestidos/síntesis química , Medios de Contraste/síntesis química , Óxido Ferrosoférrico/síntesis química , Metacrilatos/síntesis química , Nanopartículas/química , Fosforilcolina/análogos & derivados , Materiales Biocompatibles Revestidos/química , Medios de Contraste/química , Óxido Ferrosoférrico/química , Imagen por Resonancia Magnética/métodos , Metacrilatos/química , Microscopía Electrónica de Transmisión , Nanopartículas/ultraestructura , Fosforilcolina/síntesis química , Fosforilcolina/química , Ácidos Polimetacrílicos
16.
Langmuir ; 22(14): 6153-60, 2006 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-16800670

RESUMEN

The effect of varying both the solution pH and copolymer concentration on the structure of layers of poly[2-(methacryloyloxy)ethyl phosphorylcholine-block-2-(dimethylamino)ethyl methacrylate] copolymer (denoted as MPC(30)-DMA(60), M(n) = 18,000) adsorbed at the air/water interface is studied using surface tension and specular neutron reflection. The surface structure of the adsorbed diblock copolymer is represented by a dense layer of 10-15 A on the air side, accompanied by a loose layer of 20-30 A extending into the aqueous phase. Although the uniform layer model generally provided a reasonable description of the adsorbed copolymer chains, some deviations were observed. A more detailed analysis showed that the distribution of the copolymer across the interface required a minimum of three layers to take into account the structural inhomogeneities. Refinement of the structural distributions involved the combined fitting of partially deuterated copolymer in null reflecting water and D(2)O and the fully hydrogenated copolymer in D(2)O, leading to a substantial improvement in the reliability of the structural profiles obtained. The data analysis showed an increase in surface excess at higher copolymer concentrations and at more alkaline pH. However, the copolymer layer was fully immersed in water under all conditions studied. Because the surface excess showed a steady increase across the cmc over the high pH range, we speculate that copolymer adsorption above the cmc involves the formation of surface micellar aggregates under these conditions.


Asunto(s)
Materiales Biocompatibles/química , Membranas Artificiales , Metacrilatos , Neutrones , Transición de Fase , Fosforilcolina , Adsorción , Óxido de Deuterio/química , Concentración de Iones de Hidrógeno , Tensión Superficial
18.
Langmuir ; 21(8): 3591-8, 2005 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-15807606

RESUMEN

Poly[2-(dimethylamino)ethyl methacrylate-b-2-methacryloyloxyethyl phosphorylcholine] (DMA-MPC) is currently under investigation as a new vector candidate for gene therapy. The DMA block has been previously demonstrated to condense DNA effectively. The MPC block contains a phosphorylcholine (PC) headgroup, which can be found naturally in the outside of the cell membrane. This PC-based polymer is extremely hydrophilic and acts as a biocompatible steric stabilizer. In this study, we assess in detail the morphologies of DNA complexes obtained using the diblock copolymer series DMA(x)MPC30 (where the mean degree of polymerization of the MPC block was fixed at 30 and the DMA block length was systematically varied) using transmission electron microscopy (TEM) and liquid atomic force microscopy (AFM). Both techniques indicate more compact complex morphologies (more efficient condensation) as the length of the cationic DMA block increases. However, the detailed morphologies of the DMA(x)MPC30-DNA complexes observed by TEM in vacuo and by AFM in aqueous medium are different. This phenomena is believed to be related to the highly hydrophilic nature of the MPC block. TEM studies revealed that the morphology of the complexes changes from loosely condensed structures to highly condensed rods, toroids, and oval-shaped particles as the DMA moiety increases. In contrast, morphological changes from plectonemic loops to flower-like and rectangular block-like structures, with an increase in highly condensed central regions, are observed by in situ AFM studies. The relative population of each structure is clearly dependent on the polymer molecular composition. Enzymatic degradation assays revealed that only the DMA homopolymer provided effective DNA protection against DNase I degradation, while other highly condensed copolymer complexes, as judged from TEM and gel electrophoresis, only partially protected the DNA. However, AFM images indicated that the same highly condensed complexes have less condensed regions, which we believe to be the initiation sites for enzymatic attack. This indicates that the open structures observed by AFM of the DNA complexation by the DMA(x)MPC30 copolymer series are closer to in vivo morphology when compared to TEM.


Asunto(s)
ADN/administración & dosificación , Técnicas de Transferencia de Gen , Metacrilatos/química , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Biopolímeros/química , Biopolímeros/farmacología , Cationes , Membrana Celular/metabolismo , ADN/química , ADN/metabolismo , Desoxirribonucleasa I/metabolismo , Electroforesis en Gel de Agar , Terapia Genética , Metacrilatos/farmacología , Microscopía de Fuerza Atómica , Microscopía Electrónica de Transmisión , Conformación de Ácido Nucleico , Fosforilcolina/química
19.
Biomacromolecules ; 6(2): 1085-96, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15762681

RESUMEN

Two synthetic routes to folic acid (FA)-functionalized diblock copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and either 2-(dimethylamino)ethyl methacrylate [DMA] or 2-(diisopropylamino)ethyl methacrylate [DPA] were explored. The most successful route involved atom transfer radical polymerization (ATRP) of MPC followed by the tertiary amine methacrylate using a 9-fluorenylmethyl chloroformate (Fmoc)-protected ATRP initiator. Deprotection of the Fmoc groups produced terminal primary amine groups, which were conjugated with FA to produce two series of novel FA-functionalized biocompatible block copolymers. Nonfunctionalized MPC-DMA diblock copolymers have been previously shown to be effective synthetic vectors for DNA condensation; thus, these FA-functionalized MPC-DMA diblock copolymers appear to be well suited to gene therapy applications based on cell targeting strategies. In contrast, the FA-MPC-DPA copolymers are currently being evaluated as pH-responsive micellar vehicles for the delivery of highly hydrophobic anticancer drugs.


Asunto(s)
Materiales Biocompatibles/síntesis química , Portadores de Fármacos/síntesis química , Ácido Fólico , Polímeros/síntesis química , Composición de Medicamentos , Terapia Genética , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Molecular , Polímeros/uso terapéutico
20.
J Microsc ; 217(Pt 3): 216-24, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15725125

RESUMEN

A technique is described that allows the staining and subsequent visualization of polymers that contain the phosphorylcholine (PC) group. These materials are useful as bulk materials or coatings for the fabrication of medical devices. The staining method employs rhodamine 6G, which can be simply and rapidly applied to the polymer coating and imaged using fluorescence microscopy. The specificity of the staining for the PC polymers makes this technique suitable for the evaluation of a wide range of substrates and provides qualitative information on coating uniformity, coverage and morphology. It can be used to examine the durability of, and defects in, the coating. Statistical analysis of the fluorescent intensity by measuring the pixel value during imaging can allow for the method to be used as a quality control tool.


Asunto(s)
Materiales Biocompatibles/química , Microscopía Fluorescente/métodos , Fosfolípidos/química , Fosforilcolina/química , Rodaminas/química , Polímeros/química , Coloración y Etiquetado
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