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1.
Rev Med Liege ; 77(7-8): 443-447, 2022 Jul.
Artículo en Francés | MEDLINE | ID: mdl-35924500

RESUMEN

Cholelithiasis is rare in children and even more so in infants. We report the case of a 3-month-old patient with cholestatic jaundice secondary to an obstruction of the terminal portion of the bile duct. The treatment applied in this patient was a cholecystectomy with trans-cystic cholangiography and common bile duct clearance. The evolution was excellent. The current literature on biliary lithiasis in children and infants is poor in large cohort studies. The various treatments proposed, if necessary, include biliary lavage by percutaneous puncture, endoscopic retrograde cholangiopancreatography with sphincterotomy and laparoscopic or open cholecystectomy with intraoperative cholangiography. None of these procedures has shown superiority over the others. Therefore, no treatment algorithm is currently defined. Patients are treated on a case-by-case basis according to their symptoms, previous history and the level of expertise of each centre for these rare, difficult and specific procedures.


La pathologie lithiasique biliaire est rare chez l'enfant et encore plus chez le nourrisson. Nous exposons le cas d'une jeune patiente de 3 mois présentant un ictère cholestatique secondaire à un obstacle de la portion terminale du cholédoque. Le traitement appliqué chez cette patiente a été une cholécystectomie avec cholangiographie trans-cystique et désobstruction du cholédoque. L'évolution a été excellente. La littérature actuelle sur la pathologie lithiasique biliaire de l'enfant et du nourrisson est pauvre en études de grande cohorte. Les différents traitements proposés, si nécessaire, comportent le lavage biliaire par ponction percutanée, la cholangiopancréatographie rétrograde endoscopique avec sphinctérotomie et la cholécystectomie par voie laparoscopique ou ouverte avec cholangiographie peropératoire. Aucune de ces procédures n'a montré de supériorité par rapport aux autres. Aucun algorithme de traitement n'est donc actuellement défini. Les patients sont traités au cas par cas selon leurs symptômes, leurs antécédents et le niveau d'expertise de chaque centre pour ces procédures rares, difficiles et spécifiques.


Asunto(s)
Colecistectomía Laparoscópica , Colelitiasis , Laparoscopía , Niño , Colangiografía , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomía , Colecistectomía Laparoscópica/efectos adversos , Colecistectomía Laparoscópica/métodos , Colelitiasis/complicaciones , Colelitiasis/diagnóstico , Colelitiasis/cirugía , Humanos , Lactante
2.
Int J Cosmet Sci ; 39(4): 393-401, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28067963

RESUMEN

OBJECTIVE: The aim of this work was to use the contact angle measurement in order to predict the behaviour of ingredients and finished cosmetic products on skin to improve skin feel and product texture. METHOD: Different classes of cosmetic ingredients and formulations were evaluated. The contact angle measurements were carried out by the sessile drop method using an apparatus, designed and set up in laboratory. Glass, Teflon and human skin were the reference substrates. In a preliminary phase, TEWL parameter, sebum content and hydration of human skin were measured to set up method. RESULTS: Data demonstrated that glass substrate may be used as replacement of the skin:critical surface tension of skin and glass were about of 27 and 31 dyne cm-1 , respectively. Non-ionic surfactant with increasing HLB was evaluated: a correlation between contact angle measured and HLB was not observed because of different and complex molecular structure. In detail, ethylhexyl hydroxystearate (θglass = 17.1°) showed lower contact angle value with respect to Polysorbate 20 (θglass = 28.1°). Sodium laureth sulphate and stearalkonium chloride were also evaluated: anionic molecule showed more affinity for glass with respect to Teflon (θglass = 21.7° and θTeflon = 52.3°). Lipids and silicones showed different affinity for substrate according to hydrophilic groups and hydrocarbon chain: contact angles of silicones remained unchanged independently from substrate. Finished cosmetic products (O/W, W/O emulsions, cleansing oil, dry skin oil) showed different profiles according to surfactant and its affinity for continuous phase of the formulation. Comparing the values of the contact angle on skin of non-ionic surfactants, as ethylhexyl hydroxystearate and Polysorbate 20, they showed values lower (near to zero) than ones of sodium laureth sulphate and Stearalkonium Chloride (21.7° and 66.8°, respectively). Finally, finished cosmetic products tested on human skin showed different profile: corresponded contact angle values were less than 20°. The product tended to be quickly adsorbed on human skin. CONCLUSION: Systematic study carried out by evaluating the wettability of single cosmetic ingredients on different substrates allowed to find correlations between the use of certain ingredients and the final performance of a cosmetic product.


Asunto(s)
Cosméticos , Piel , Humectabilidad , Femenino , Humanos , Técnicas In Vitro , Masculino , Tensión Superficial
3.
J Pharm (Cairo) ; 2013: 386546, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-26555976

RESUMEN

Bladder pain is a characteristic disorder of interstitial cystitis. Diazepam is well known for its antispasmodic activity in the treatment of muscular hypertonus. The aim of this work was to develop and characterize vaginal pessaries as an intravaginal delivery system of diazepam for the treatment of interstitial cystitis. In particular, the performance of two types of formulations, with and without beta-glucan, was compared. In particular, the preparation of pessaries, according to the modified Pharmacopeia protocol, the setup of the analytical method to determine diazepam, pH evaluation, dissolution profile, and photostability assay were reported. Results showed that the modified protocol permitted obtaining optimal vaginal pessaries, without air bubbles, with good consistency and handling and with good pH profiles. In order to determine the diazepam amount, calibration curves with good correlation coefficients were obtained, by the spectrophotometric method, using placebo pessaries as matrix with the addition of diazepam standard solution. This method was demonstrated sensible and accurate to determine the amount of drug in batches. Dissolution profiles showed a complete diazepam release just after 15 minutes, even if beta-glucan pessaries released drug more gradually. Finally, a possible drug photodegradation after exacerbated UV-visible exposition was evaluated.

4.
J Microencapsul ; 27(3): 253-62, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20406095

RESUMEN

New formulation strategies have to be developed to limit the skin penetration of UV-filter. Nanoparticles (NP) are very suitable for that purpose. In this study, the skin distribution, at different times (1, 2 and 3 h), of octyl-methoxycinnamate (OMC) from loaded PLA-nanoparticles was compared to a classical formulation containing non-encapsulated OMC, using the Franz cell method. The results showed that the OMC penetration was clearly impeded by stratum corneum and that the major part of the OMC-NP was accumulated at the skin surface (> 80%). A significant lower OMC amount was quantified in viable skin with NP compared to the OMC emulgel. To accurately determine the real OMC amount in close contact with viable skin layers two solvents were used to extract OMC from the skin compartments. Acetone (ACET) allowed quantifying both OMC in NP and OMC released from the particles, while isopropylmyristate (IPM), a non-solvent of the NP polymer (PLA), allowed quantifying only OMC released from the particles. Using IPM as an extraction solvent, it appeared that the OMC released from NP, in contact with viable skin, was 3-fold lower than free OMC diffused from the emulgel. Lastly, a sustained release was observed when nanoparticles were used.


Asunto(s)
Cinamatos/administración & dosificación , Nanopartículas/química , Poliésteres/química , Absorción Cutánea , Piel/metabolismo , Protectores Solares/administración & dosificación , Animales , Cinamatos/farmacocinética , Nanopartículas/ultraestructura , Protectores Solares/farmacocinética , Porcinos
6.
AAPS PharmSciTech ; 9(2): 718-25, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18528761

RESUMEN

To evaluate the effects of different gamma irradiation doses on PEGd,lPLA and PEG-PLGA multiblock copolymers. The behaviour of the multiblock copolymers to irradiation was compared to that of PLA, PLGA polymers. PEGd,lPLA, PEG-PLGA, PLA and PLGA polymers were irradiated by using a (60)Co irradiation source at 5, 15, 25 and 50 kGy total dose. Characterization was performed on all samples before and after irradiation, by nuclear magnetic resonance (NMR), infrared absorption spectrophotometry (FTIR) and gel permeation chromatography (GPC). The effect of gamma irradiation on polymer stability was also evaluated. Results of NMR and FTIR suggest an increase in -OH and -COOH groups, attributed to scission reactions induced by irradiation treatment. Data of GPC analysis showed that the weight average molecular weight (Mw) of polymer samples decreased with increasing irradiation dose. The extent of Mw degradation expressed as percentage of Mw reduction was more prominent for polymers with high molecular weight as PEGd,lPLA and PLA. The dominant effect of gamma-irradiation on both polymer samples was chain scission. The multiblock copolymer PEGd,lPLA presented higher sensitivity to irradiation treatment with respect to PLA, likely due to the presence of PEG in the matrix. The effect of gamma irradiation continues over a much longer period of time after gamma irradiation has been performed. It is suggested that the material reacts with oxygen to form peroxyl free radicals, which may further undergo degradation reactions during storage after irradiation.


Asunto(s)
Portadores de Fármacos , Rayos gamma , Lactatos/efectos de la radiación , Polietilenglicoles/efectos de la radiación , Poliglactina 910/efectos de la radiación , Esterilización/métodos , Cromatografía en Gel , Relación Dosis-Respuesta en la Radiación , Lactatos/química , Espectroscopía de Resonancia Magnética , Modelos Químicos , Estructura Molecular , Peso Molecular , Oxígeno/química , Peróxidos/química , Polietilenglicoles/química , Poliglactina 910/química , Espectroscopía Infrarroja por Transformada de Fourier , Factores de Tiempo
7.
Int J Pharm ; 358(1-2): 230-7, 2008 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-18455892

RESUMEN

The first aim of this work was to perform site-directed PEGylation of the enzyme prolidase at sulphydril groups by methoxy-polyethylene glycol-maleimide (Mal-PEG, Mw 5000 Da) in order to obtain a safe conjugation product more stable than the native enzyme. Prolidase is a cytosolic aminoacyl-l-proline hydrolase whose deficiency causes the onset of rare autosomal recessive disorder called prolidase deficiency (PD). The second purpose of this work was to investigate whether biodegradable chitosan nanoparticles loaded with PEGylated prolidase could be effective in releasing active enzyme inside fibroblasts as a possible therapeutic approach for PD. The SDS-PAGE analysis and the ESI-MS spectra confirmed the presence of the PEGylated prolidase: in particular the main conjugation product (m/z=about 65,000 Da) corresponded to the enzyme with two residues of Mal-PEG. In this study it was demonstrated the lack of toxicity (MTT assay) and the prolonged activity (40.6+/-2.6% after 48h of incubation at 37 degrees C) of the PEGylated enzyme. The PEGylated prolidase loaded chitosan nanoparticles had spherical shape, narrow size distribution (271.6+/-45.5 nm), a positive zeta-potential (15.93+/-0.26 mV) with a good preparation yield (54.6+/-3.6%) and protein encapsulation efficiency (44.8+/-4.6%). The ex vivo evaluation of prolidase activity on PD fibroblasts individuated a good level of prolidase activity replaced (about 72% after only 2 days of incubation) up to 10 days with improved morphological cell features.


Asunto(s)
Dipeptidasas/administración & dosificación , Dipeptidasas/uso terapéutico , Polietilenglicoles/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Dipeptidasas/química , Portadores de Fármacos , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Electroforesis en Gel de Poliacrilamida , Fibroblastos/efectos de los fármacos , Humanos , Maleimidas/química , Microscopía Electrónica de Transmisión , Nanopartículas , Espectrometría de Masa por Ionización de Electrospray , Compuestos de Sulfhidrilo/química
8.
Int J Cosmet Sci ; 30(3): 219-27, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18452438

RESUMEN

The use of sunscreens is the 'gold standard' for protecting the skin from ultraviolet light. Octyl methoxycinnamate (OMC) is one of the most widely used UVB filter but it can act as a sensitizer or photoallergen. When exposed to sunlight, OMC can change from the primary trans-form to cis-form and the isomerization, not reversible, conducts to a reduction of the UVB filtering efficiency because the trans-form has a higher extinction coefficient. Photostability is the most important characteristic of effective sunscreens and it can be influenced by formulation ingredients and by applying technological strategies. In this work, photostability experiments, performed on emulsion-gels containing different percentages of OMC free or loaded in poly(D,L-lactide) nanoparticles, were carried out. The presence of a polymeric envelop may act to protect the active ingredient. In this study, the influence of poly(D,L-lactide) matrices on the photochemical stability of the sunscreen agent was investigated. As highlighted in this study, free OMC in different formulations has different photoisomerization degree. Moreover, a dissimilar behaviour was observed by studying different sunscreen concentrations in the same cosmetic formulation. Photostability results show a significant reduction in photoisomerization degree for formulations containing sunscreen loaded in nanoparticles, highlighting that the encapsulation is a suitable strategy to improve OMC photostability. Moreover, sun protection factor (SPF) results show that the UVB filter protective power is also maintained after encapsulation.


Asunto(s)
Cinamatos/química , Nanopartículas/química , Poliésteres/química , Protectores Solares/química , Cinamatos/efectos de la radiación , Estabilidad de Medicamentos , Emulsiones/química , Isomerismo , Espectrofotometría Ultravioleta , Protectores Solares/efectos de la radiación , Rayos Ultravioleta
9.
J Microencapsul ; 25(5): 330-8, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18465305

RESUMEN

PURPOSE: To prepare and characterize polyethylenglycol-co-poly-D,L-lactide (PEG-D,L-PLA) multiblock copolymer microspheres containing ovalbumin. Microsphere batches made of Poly-D,L-lactide (PLA) homopolymers were prepared in order to evaluate how the presence of PEG segments into PEG-D,L-PLA copolymer could affect the behaviour of microspheres as carrier of protein drugs. METHODS: The PEG-D,L-PLA and PLA microspheres, loaded with the model protein ovalbumin, were prepared using double emulsion solvent evaporation method. The effect of PEG segments in the microparticles matrix, on the morphology, size distribution, encapsulation efficiency and release behaviour was studied. RESULTS: According to the results, PEG-D,L-PLA microspheres were more hydrophilic than PLA microparticles and with lower glass transition temperature. The surface of PEG-D,L-PLA microspheres was not as smooth as that of PLA microparticles, the mean diameter of PEG-D,L-PLA microparticles was bigger than that of PLA microspheres. Protein release from the microspheres was affected by the morphological structure of PEG-D,L-PLA microspheres and properties of PEG-D,L-PLA copolymer. This study suggests that PEG-D,L-PLA multiblock copolymer may be used as carrier in protein delivery systems for different purposes.


Asunto(s)
Lactatos/química , Microesferas , Ovalbúmina/química , Polietilenglicoles/química , Química Farmacéutica/métodos , Portadores de Fármacos , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Diseño de Fármacos , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Peso Molecular , Polímeros/química , Cloruro de Sodio/química , Temperatura
10.
Int J Cosmet Sci ; 30(2): 113-20, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18377620

RESUMEN

Oleuropein, a phenolic compound derived from olive leaves and oil, is known to possess several biological properties, many of which may be attributed to its antioxidant and free radical-scavenging activities. Nevertheless, up to now, the cosmetic activity of this molecule has not been extensively investigated. The aim of this work was to evaluate the cosmetic properties of oleuropein against UVB-induced erythema. To this end, an emulsion and an emulgel containing oleuropein were prepared, applied and evaluated on healthy volunteers who had undergone UVB irradiation to investigate its protective and/or lenitive activity. Protective effect was assayed by application of topical preparations before irradiation and lenitive effect was evaluated after erythema induction. Vitamin E was used as the reference compound. Our study was carried out by using noninvasive techniques to assess specific skin parameters: barrier function, skin colour and microcirculation. Results clearly showed that oleuropein formulations highlighted lenitive efficacy by reducing erythema, transepidermal water loss and blood flow of about 22%, 35% and 30% respectively. The study allowed us to point out the lenitive property of oleuropein, opening the way to further trials to deepen our specific knowledge about this natural molecule, which could be used in association with other active ingredients in cosmetics to repair UV damages.


Asunto(s)
Antioxidantes/administración & dosificación , Cosméticos/administración & dosificación , Eritema/prevención & control , Piranos/administración & dosificación , Administración Tópica , Adulto , Antioxidantes/química , Cromatografía Líquida de Alta Presión , Cosméticos/química , Emulsiones/administración & dosificación , Emulsiones/química , Eritema/etiología , Femenino , Humanos , Glucósidos Iridoides , Iridoides , Olea/química , Proyectos Piloto , Hojas de la Planta/química , Piranos/química , Piel/efectos de los fármacos , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos
11.
J Microencapsul ; 22(5): 459-70, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16361190

RESUMEN

The objective of this study was to prepare a microparticulate drug delivery system being based on a new thiomer, namely a chitosan 2-iminothiolane conjugate (chitosan-TBA conjugate). Due to thiol groups being immobilized on chitosan, chitosan-TBA conjugate exhibits improved mucoadhesive and permeation enhancing properties. Because of these features microparticulate drug delivery systems based on chitosan-TBA conjugate might be a promising tool for the non-invasive administration of hydrophilic macromolecular drugs. Chitosan-TBA conjugate microspheres were prepared by the emulsification/solvent evaporation method. Fluorescein-isothiocyanate labelled dextran (FITC-dextran) was chosen as a model hydrophilic drug. Microspheres have been characterized by morphological analysis, thiol group content, swelling behaviour, polymer degradation drug load determination, dissolution test and mucoadhesion studies. Results reported in this work demonstrated the possibility to obtain stable microspheres without cross-linking agents. Thiolated chitosan microspheres seem to be more stable in aqueous media with respect to unmodified chitosan. The degradability by lysozyme appears quite similar for both polymers, showing that chemical modification does not influence the biodegradable properties of chitosan. Microspheres were able to control the drug release for at least 1 h, exhibiting comparatively strong mucoadhesive properties. The chitosan-TBA conjugate microparticles remain on the mucosa in a 2.5-fold higher concentration with respect to unmodified chitosan microparticles. These data suggest that chitosan-TBA conjugate microspheres have the potential to be used as a mucoadhesive drug delivery system.


Asunto(s)
Microesferas , Adhesividad , Animales , Materiales Biocompatibles , Biodegradación Ambiental , Quitosano/análogos & derivados , Preparaciones de Acción Retardada , Dextranos , Composición de Medicamentos/métodos , Estabilidad de Medicamentos , Fluoresceína-5-Isotiocianato , Colorantes Fluorescentes , Mucosa Intestinal/fisiología , Microscopía Electrónica de Rastreo/métodos , Membrana Mucosa/fisiología , Muramidasa , Compuestos de Sulfhidrilo , Propiedades de Superficie , Porcinos
12.
J Pharm Pharmacol ; 56(5): 597-603, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15142336

RESUMEN

Prolidase deficiency (PD) is a rare autosomal recessive disorder caused by inadequate levels of the cytosolic exopeptidase prolidase (E.C. 3.4.13.9), for which there is not, as yet, a resolutive cure. We have investigated whether biodegradable microspheres loaded with prolidase could release active enzyme inside cells, to consider this system as a possible therapeutic approach for prolidase deficiency. Poly(lactide-co-glycolide) microspheres were prepared, modifying the classical double emulsion solvent evaporation method to mitigate the burst effect of the enzyme from the microspheres. Ex-vivo experiments were performed, by incubating microencapsulated prolidase with cultured fibroblasts from PD patients and from controls, to determine the amount of active enzyme delivered to the cells. The microparticulate drug delivery system described carried small amounts of active prolidase inside fibroblasts, ensuring a response to the intracellular accumulation of X-Pro dipeptides, the mechanism that is supposed to be responsible for the development of clinical manifestations of this disorder in man. A positive result of the presence of active enzyme inside cells was an improvement in fibroblast shape.


Asunto(s)
Dipeptidasas/administración & dosificación , Dipeptidasas/metabolismo , Fibroblastos/efectos de los fármacos , Poliglactina 910/química , Biodegradación Ambiental , Células Cultivadas , Dipeptidasas/deficiencia , Portadores de Fármacos/química , Activación Enzimática/efectos de los fármacos , Fibroblastos/enzimología , Humanos , Microesferas , Piel/citología , Factores de Tiempo
13.
Int J Pharm ; 256(1-2): 153-60, 2003 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-12695021

RESUMEN

The aim of this work was to prepare and to evaluate "in vitro"/"in vivo" microspheres based on poly(D,L-lactide-co-glycolide) copolymers containing ipriflavone, for the local treatment of oral bone loss. The first objective was the preparation and "in vitro" characterization of ipriflavone loaded microspheres, by emulsion/solvent evaporation method. Process parameters such as drug:polymer weight ratio, and molecular weight of copolymers, were also investigated. The second objective was to elaborate a suitable animal model of mandibular osteoporosis, to evaluate the efficacy of these microparticulate drug delivery systems. "In vivo" experiments were carried out on female rats, in which oral osteopenia was induced by gonadectomy and molar avulsion. Morphometric analysis of mandibular segment were carried out to quantify the development of oral osteopenia and the efficacy of drug loaded microspheres. Results showed that ipriflavone loaded PLGA microspheres can be successfully obtained with good "in vitro" characteristics, utilizing the emulsification/solvent evaporation method. "In vivo" experiments revealed that local administration of microspheres produced only mild inflammation on the injection site. Morphometric analyses showed, at the level of the third molar, a slight increase in spongy and total bone mass on rat jaw treated with microspheres with respect to control. Control animals exhibited a scarce degree of osteopenia demonstrating that this animal model is not suitable for this purpose.


Asunto(s)
Isoflavonas/uso terapéutico , Ácido Láctico/química , Osteoporosis/tratamiento farmacológico , Ácido Poliglicólico/química , Polímeros/química , Animales , Remodelación Ósea/efectos de los fármacos , Remodelación Ósea/fisiología , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Composición de Medicamentos , Femenino , Inyecciones , Isoflavonas/química , Maxilares/efectos de los fármacos , Microesferas , Peso Molecular , Osteoporosis/fisiopatología , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ratas , Ratas Sprague-Dawley , Solubilidad
14.
Int J Pharm ; 252(1-2): 1-9, 2003 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-12550776

RESUMEN

The aim of the present work was to design a film dosage form for sustained delivery of ipriflavone into the periodontal pocket. For this purpose, monolayer composite systems made of ipriflavone loaded poly(D,L-lactide-co-glycolide) (PLGA) micromatrices in a chitosan film form, were obtained by emulsification/casting/evaporation technique. Multilayer films, made of three layers of polymers (chitosan/PLGA/chitosan), were also prepared and compared to monolayer films for their "in vitro" characteristics. Morphology and physico-chemical properties of the different systems were evaluated. The influence of pH, ionic strength and enzymatic activity on film degradation, was also investigated. Significant differences in swelling, degradation and drug release were highlighted, depending on film structure and composition. In vitro experiments demonstrated that the composite micromatricial films represent a suitable dosage form to prolong ipriflavone release for 20 days.


Asunto(s)
Quitina/análogos & derivados , Quitina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Isoflavonas/administración & dosificación , Ácido Láctico/administración & dosificación , Bolsa Periodontal/tratamiento farmacológico , Ácido Poliglicólico/administración & dosificación , Polímeros/administración & dosificación , Quitina/farmacocinética , Quitosano , Isoflavonas/farmacocinética , Ácido Láctico/farmacocinética , Lípidos/administración & dosificación , Lípidos/farmacocinética , Bolsa Periodontal/metabolismo , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/farmacocinética , Solubilidad
15.
J Microencapsul ; 19(5): 591-602, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12433302

RESUMEN

This work was aimed at studying enzyme prolidase stability and its interactions with the reagents and the process conditions involved in preparation, by an emulsification process, of prolidase loaded poly(lactide-co-glycolide) (PLGA) microparticulate systems. Enzyme stability was tested with respect to contact with methylene chloride, ethyl acetate, PLGA polymers, and several agents used as emulsifiers such as polyvinyl alcohol (PVA), polyvinyl pyrolidone (PVP), carboxymethyl cellulose (CMC) and sodium oleate (NaOl). Enzyme stability to temperature and mechanical stirring was also evaluated. Prolidase-loaded PLGA microspheres were prepared and evaluated in terms of protein activity. The results obtained showed that the prolidase-loaded PLGA microspheres can be prepared only upon enzyme stabilization by addition of both BSA and MnCl(2) into its TRIS solution. Methylene chloride was the suitable organic solvent to be used in the double emulsion process, together with PVA as dispersing agent in the outer aqueous phase. Low temperatures during the emulsification step and very short process times are recommended, in order to maintain enzyme activity at its maximum. In these conditions spherical microspheres were obtained, releasing active prolidase for up to 15 days.


Asunto(s)
Dipeptidasas/administración & dosificación , Dipeptidasas/química , Ácido Láctico/química , Ácido Poliglicólico/química , Polímeros/química , Animales , Cápsulas/química , Dipeptidasas/metabolismo , Composición de Medicamentos , Emulsiones , Estabilidad de Enzimas , Técnicas In Vitro , Microscopía Electrónica de Rastreo , Microesferas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Resistencia al Corte , Solventes , Porcinos
16.
Int J Pharm ; 246(1-2): 37-45, 2002 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-12270607

RESUMEN

The aim of this study was to investigate the influence of nanoparticle-based systems on the light-induced decomposition of the sunscreen agent, trans-2-ethylhexyl-p-methoxycinnamate (trans-EHMC). Ethylcellulose (EC) and poly-D,L-lactide-co-glycolide (PLGA) were used as biocompatible polymers for the preparation of the particulate systems. The "salting out" method was used for nanoparticle preparation and several variables were evaluated in order to optimize product characteristics. The photodegradation of the sunscreen agent in emulsion vehicles was reduced by encapsulation into the PLGA nanoparticles (the extent of degradation was 35.3% for the sunscreen-loaded nanoparticles compared to 52.3% for free trans-EHMC) whereas the EC nanoparticle system had no significant effect. Therefore, PLGA nanoparticles loaded with trans-EHMC improve the photostability of the sunscreen agent.


Asunto(s)
Celulosa/análogos & derivados , Cinamatos/efectos de la radiación , Protectores Solares/efectos de la radiación , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Cinamatos/química , Portadores de Fármacos , Estabilidad de Medicamentos , Cromatografía de Gases y Espectrometría de Masas , Ácido Láctico , Espectroscopía de Resonancia Magnética , Nanotecnología , Tamaño de la Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros , Estereoisomerismo , Protectores Solares/química , Rayos Ultravioleta
17.
J Control Release ; 77(3): 287-95, 2001 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-11733096

RESUMEN

Prolidase is a naturally occurring enzyme involved in the final stage of protein catabolism. Deficient enzyme activity causes prolidase deficiency (PD), a rare autosomal recessive inherited disorder whose main manifestations are chronic, intractable ulcerations of the skin, particularly of lower limbs. Although several attempts have been made towards the treatment of this pathology, a cure for this disease has yet to be found. The purpose of this work is to evaluate the possibility of enzyme replacement therapy through prolidase microencapsulation in biodegradable microspheres. The poly(D,L-lactide-co-glycolide) (PLGA) prolidase loaded microparticulate systems have been prepared utilizing the w-o-w double emulsion solvent evaporation method. They have been characterized "in vitro" by morphological analysis, total protein content and an in vitro dissolution test of active protein. "Ex vivo" evaluation of prolidase activity from the microspheres has been performed on cellular extracts of cultured skin fibroblasts from healthy subjects (controls) and from patients affected by PD. The results reported in this work on prolidase from pig kidney (available on the market) demonstrate the positive role of microencapsulation as a process of enzymatic activity stabilization inside PLGA microspheres achieving both in vitro and ex vivo active enzyme release. This formulation can be proposed as a parenteral depot drug delivery system.


Asunto(s)
Evaluación de Medicamentos/métodos , Enzimas Inmovilizadas/farmacocinética , Adulto , Animales , Biodegradación Ambiental , Células Cultivadas , Dipeptidasas/administración & dosificación , Dipeptidasas/farmacocinética , Activación Enzimática/fisiología , Enzimas Inmovilizadas/administración & dosificación , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Humanos , Masculino , Microesferas , Persona de Mediana Edad , Piel/efectos de los fármacos , Piel/enzimología , Porcinos
18.
AAPS PharmSciTech ; 2(3): E10, 2001 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-14727869

RESUMEN

This paper describes the formulation of a biodegradable microparticulate drug delivery system containing clodronate, a bisphosphonate intended for the treatment of bone diseases. Microspheres were prepared with several poly(D,L-lactide-co-glycolide) (PLGA) copolymers of various molecular weights and molar compositions and 1 poly(D,L-lactide) (PDLLA) homopolymer by a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation procedure. Critical process parameters and formulation variables (ie, addition of stabilizing agents) were evaluated for their effect on drug encapsulation efficiency and clodronate release rate from microparticles. Well-formed clodronate-loaded microspheres were obtained for all polymers by selecting suitable process parameters (inner water/oil volume ratio 1:16, temperature-raising rate in the solvent evaporation step 1 degree C/min, 2% wt/vol NaCl in the external aqueous phase). Good yields were obtained in all batches of clodronate microspheres (above 60%); drug encapsulation efficiencies ranged between 49% and 75% depending on the polymer used. Clodronate release from all copolymer microspheres was completed in about 48 hours, while those from PDLLA microspheres required about 20 days. The change of microsphere composition by adding a surfactant such as Span 20 or a viscosing agent such as carboxymethylcellulose extended the long-term release up to 3 months. Clodronate was successfully entrapped in PLGA and PDLLA microspheres, and drug release could be modulated from 48 hours up to 3 months by suitable selection of polymer, composition, additives, and manufacturing conditions.


Asunto(s)
Ácido Clodrónico/administración & dosificación , Biodegradación Ambiental , Preparaciones de Acción Retardada , Portadores de Fármacos , Ácido Láctico , Microesferas , Tamaño de la Partícula , Poliésteres , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros , Solventes/química
19.
Drug Deliv ; 7(2): 97-103, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10892410

RESUMEN

Boronophenylalanine (BPA)-loaded conventional and stabilized liposomes were prepared by the reversed phase evaporation method to treat liver metastases by boron neutron capture therapy. Conventional vesicles were composed of phosphatidylcholine and cholesterol, molar ratio 1:1. To obtain stealth liposomes, GM1 or PEG were included in the lipidic bilayer at a concentration of 6.67 or 5 mol%, respectively. Large unilamellar vesicles were formulated encapsulating BPA in the liposome aqueous compartment as a complex with fructose; BPA free base also was embedded into the lipidic bilayer. In vivo experiments were carried out after intravenous injection of liposome suspensions in BD-IX strain rats in which liver metastases had been induced. Alpha particle spectroscopy associated with histological analysis was performed to visualize boron spatial distribution in liver. Simultaneously, tissue boron concentrations were determined using inductively coupled plasma-mass spectroscopy. Results showed that PEG-modified liposomes accumulated boron in therapeutic concentrations (> 30 micrograms boron/g tissue) in metastatic tissue. The PEG-liposomes could be further explored in enhancing boron delivery to tumor cells.


Asunto(s)
Compuestos de Boro/administración & dosificación , Terapia por Captura de Neutrón de Boro , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundario , Fenilalanina/análogos & derivados , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Animales , Autorradiografía , Liposomas , Fenilalanina/administración & dosificación , Polietilenglicoles/administración & dosificación , Ratas
20.
Int J Pharm ; 196(1): 51-61, 2000 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-10675707

RESUMEN

Glycolic acid is used in many cosmetic products as exfoliant and moisturizer. Unfortunately, the greater glycolic acid cosmetic benefits the greater is the potential for skin irritation as far as burning. The aim of this work was to investigate the feasibility of topical controlled delivery systems loading glycolic acid in order to optimize the acid cosmetic properties lowering its side effects. For this purpose different types of microparticulate systems have been evaluated: liposomes, liposomes modified by chitosan addition and chitosan microspheres. Liposomes, composed of phosphatidylcholine and cholesterol (1:1 molar ratio) and with different glycolic acid/lipid molar ratio, were prepared by reverse phase evaporation method. Two types of interaction between liposomes and chitosan were investigated: chitosan addition into lipidic bilayer during liposome preparation and coating of already formed liposomes with chitosan. Glycolic acid loaded chitosan microspheres were prepared by the dry-in-oil emulsion method. The microparticulate systems were morphologically characterized by electron microscopy and particle size analysis. In vitro dissolution tests were performed to evaluate the feasibility of microparticulate systems in modulating glycolic acid release. The results obtained show that liposomes are always suitable to modulate glycolic acid release and that the best condition to achieve this control is obtained by the liposomal systems in which glycolic acid/lipid molar ratio is 5:1. Further significant release control is obtained by addition of chitosan into the liposomes, while chitosan microspheres are not able to control glycolic acid release even after crosslinking.


Asunto(s)
Quitina/análogos & derivados , Materiales Biocompatibles Revestidos/administración & dosificación , Materiales Biocompatibles Revestidos/química , Glicolatos/administración & dosificación , Glicolatos/química , Administración Tópica , Quitina/administración & dosificación , Quitina/química , Quitosano , Colesterol/administración & dosificación , Colesterol/química , Colorimetría , Cosméticos/química , Preparaciones de Acción Retardada , Composición de Medicamentos , Liposomas , Microscopía Electrónica , Microesferas , Tamaño de la Partícula , Fosfatidilcolinas/administración & dosificación , Fosfatidilcolinas/química
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