Biodegradable double cross-linked chitosan hydrogels for drug delivery: Impact of chemistry on rheological and pharmacological performance.

This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the chosen ionic and covalent cross-linker, respectively. The novel hydrogels completely disintegrated within 96 h by means of a hydrolysis process mediated by the enzyme trehalase. As far as the authors are aware, this is the first time that a trehalose derivative has been used as a covalent cross-linker in the formation of biodegradable hydrogels. The impact of CTS concentration and degree of cov-XrL on rheological parameters were examined by means of an experimental model design and marked differences were found between the materials. Hydrogels with maximum elastic properties were achieved at high CTS concentrations and high degrees of cov-XrL. DCNa-loaded formulations displayed well-controlled drug-release profiles strongly dependent on formulation composition (from 17% to 40% in 72 h). Surprisingly, higher degrees of covalent cross-linking led to a boost in drug release. The formulations presented herein provides a simple and straightforward pathway to design fully biodegradable, tailor-made controlled drug delivery systems with improved rheological properties.

Nanostructured Chitosan-Based Biomaterials for Sustained and Colon-Specific Resveratrol Release.

In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic effects on inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box⁻Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 °C and at RES/polymer ratio of 0.75:1 w/w. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79⁻81%), and the CTS-NPs composites (29⁻34%).

Loading studies of the anticancer drug camptothecin into dual stimuli-sensitive nanoparticles. Stability scrutiny.

In recent years, the preparation of valuable drug delivery systems (DDS) from self-assembled amphiphilic copolymers has attracted much attention since these nanomaterials provide new opportunities to solve problems such as the lack of solubility in water of lipophilic drugs, improve their bioavailability, prolong their circulation time and decrease the side effects associated with their administration. In the current study two types of biocompatible pH-responsive nanoparticles derived from poly(2-hydroxyethyl methacrylate) (pHEMA) have been used as drug nano-carriers, being one of them core cross-linked to circumvent their instability upon dilution in human fluids. The present paper deals with the optimization of the loading process of the labile, hydrophobic and highly active anticancer drug, Camptothecin (CPT) into the nanoparticles with regard to four independent variables: CPT/polymer ratio, sonication, temperature and loading time. Forty experiments were carried out and a Box-Behnken experimental design was used to evaluate the significance of the independent variables related to encapsulation efficiency and drug retention capacity. The enhanced drug loading and encapsulation efficiency values (58% and >92%, respectively) of CPT were achieved by the core cross-linked NPs in 2 h at 32 °C at CPT/polymer ratio 1.5:1 w/w and 14 min of sonication. The optimized CPT-loaded NPs were studied by dynamic light scattering and scanning electron microscopy, and an increase in size of the loaded-NP compared to the unloaded counterparts was found. Other twenty experiments were conducted to study the enability to retain CPT into the conjugates at different ionic strength values and times. The stability studies demonstrated that the core cross-linked nanocarriers displayed an excellent drug retention capacity (>90%) at 25 °C for 15 days in every ionic-strength environments whereas the non-cross-linked ones were more stable at physiological ionic strength. The optimized systems proved to be a major step forward to encapsulate and retain CPT in the NP nuclei, what makes them ideal devices to control the delivery of CPT upon the triggered acidic conditions of solid tumors.

Evaluation of heavy metals and arsenic speciation discharged by the industrial activity on the Tinto-Odiel estuary, SW Spain.

This study reports the annual amount of heavy metals discharged by industrial activity into the estuary of the Ría of Huelva (SW Spain). The findings showed that the discharged metals found in highest amounts were Fe (11 t y⁻¹), Zn (3.4 t y⁻¹) and Mo (0.88 t y⁻¹). There were other metals with high pollutant charge, such as Ti (232 kg y⁻¹), As (228 kg y⁻¹), Ni (195 kg y⁻¹), Pb (100 kg y⁻¹), Cr (39 kg y⁻¹) and Cd (33 kg y⁻¹). These results were compared with pollutants transported via the Tinto and Odiel rivers from abandoned mining activities in the Iberian Pyrite Belt (IPB), and it was deduced that the amounts spilled exclusively by industries were less than 1% in relation to the total discharge. Hence, the treatment of residues from the IPB should be the priority goal to improve water quality in the estuary.

Effect of the previous composting on volatiles production during biomass pyrolysis.

Composting is a biological process of decomposition of organic materials in an aerobic environment, which modifies the chemical composition and the thermal behavior of biomass. During composting, fungi and bacteria promote the decomposition of hemicellulosic and cellulosic fractions, increasing the lignin proportion. Its product, compost, is usually used as an amendment to soil; however, its physicochemical characteristics turn it into an interesting feedstock in pyrolysis or gasification facilities. The changes that composting produces on biomass pyrolysis can be explained using an autocatalytic kinetic model (Prout-Tompkins). Thus, by means of a similar set of kinetic parameters for both the biomass and compost, it is possible to simulate the thermogravimetric analysis data (TG and DTG curves) of the materials as a sum of thermal degradations of its main pseudocomponents, hemicellulose, cellulose, lignin, and extractives. TG analysis coupled to mass spectrometry (MS) allows monitoring of the gas production during pyrolysis. Water and carbon oxide MS profiles can be simulated by an optimized linear combination of previously calculated DTG curves of pseudocomponents; however, in order to simulate the hydrogen MS signal, it is necessary to consider the char obtained in the course of the volatilization process. During pyrolysis, hydrogen production has two origins, volatilization of biomass pseudocomponents and charring. The last mechanism explains approximately 75% of the hydrogen obtained from compost. The pseudocomponent that produces more hydrogen by weight unit is lignin, showing a specific hydrogen production much higher than carbohydrates (3:1:8 for hemicellulose/cellulose/lignin). This fact, together with the greater lignin content in compost, explains the positive effect of composting on hydrogen production.

[Endoscopic treatment of ureterocele in children: is a long term effective technique?]. / Tratamiento endoscópico de los ureteroceles en edad pediátrica, efectivo a largo plazo?

INTRODUCTION: The endoscopic treatment of the ureterocele is a less invasive procedure. Currently, there are only a few published articles regarding the long-term outcomes of this treatment. MATERIAL AND METHODS: We have introduced this technique in our practice since 1995, and have been tracking 15 pediatric patients for long-term evaluation. RESULTS: The average operative age for endoscopic treatment is 19.40 months (1 week-8 years). In 53% of the cases, the diagnosis was made during prenatal screening. In 27% of the cases, the ureterocele was bilateral, and 47% of the patients have a double system. The indication for endoscopic treatment is 66% ureteric obstruction and 34% vesicoureteric reflux. We perform "uncapping" and incision in the two first cases and puncture in the subsequent procedure. The patients were followed for 4 years (7 months-7 years). During this time, two ureteroceles needed a second perforation, out of the seven that continued having reflux, two were treated with quimioprofilaxis and two were treated endoscopically for anti-reflux. Two patients continued to have reflux, and two were diagnosed with renal atrophy and hemiatrophy. DISCUSSION: The endoscopic treatment avoided an open surgical procedure in almost all cases. The need for anti-reflux puncture occurred in 33% of the cases.

Tratamiento endoscópico de los ureteroceles en edad pediátrica, ¿efectivo a largo plazo? / Endoscopic treatment of ureterocele in children: is a long term effective technique?

Introducción. El tratamiento endoscópico del ureterocele supone la forma menos invasiva de intervención. Pocos trabajos hablan de los resultados a largo plazo. Material y método. Desde que en 1995 se introdujo esta técnica en nuestro Servicio se ha aplicado a 15 pacientes, revisando su evolución a largo plazo. Resultados. La media de edad en el momento de la intervención es de 19,40 meses (1 semana-8 años). El diagnóstico fue prenatal en el 53% de los casos. El ureterocele es bilateral en el 27%. El 47% de los niños presentan un doble sistema. La indicación de intervención es la obstrucción ureteral en el 66% y el reflujo vesicoureteral en los demás casos. Se realiza apertura del techo e incisión en los dos primeros casos y perforación en los siguientes. El seguimiento se realiza durante 4 años de media (7 meses-7 años). En este tiempo, dos ureteroceles precisan una segunda perforación y siete presentan reflujo, tratados con quimioprofilaxis en dos y antirreflujo endoscópico en los otros. Dos mantienen reflujo y dos, atrofia y hemiatrofia renal. Discusión. El tratamiento endoscópico del ureterocele evitó la cirugía abierta en prácticamente todos los pacientes, precisando tratamiento antirreflujo en el 33% (AU)

Introduction. The endoscopic treatment of the ureterocele is a less invasive procedure. Currently, there are only a few published articles regarding the long-term outcomes of this treatment. Material and methods. We have introduced this technique in our practice since 1995, and have been tracking 15 pediatric patients for longterm evaluation. Results. The average operative age for endoscopic treatment is 19.40 months (1 week-8 years). In 53% of the cases, the diagnosis was made during prenatal screening. In 27% of the cases, the ureterocele was bilateral, and 47% of the patients have a double system. The indication for endoscopic treatment is 66% ureteric obstruction and 34% vesicoureteric reflux. We perform «uncapping» and incision in the two first cases and puncture in the subsequent procedure. The patients were followed for 4 years (7 months-7 years). During this time, two ureteroceles needed a second perforation, out of the seven that continued having reflux, two were treated with quimioprofilaxis and two were treated endoscopically for anti-reflux. Two patients continued to have reflux, and two were diagnosed with renal atrophy and hemiatrophy. Discussion. The endoscopic treatment avoided an open surgical procedure in almost all cases. The need for anti-reflux puncture occurred in 33% of the cases (AU)

[Cystic angiomatosis]. / Angiomatosis quística.

A case of cystic angiomatosis is presented in a patient whose clinical sign were the presence of an inguinoescrotal mass due to a retroperitoneal lymphangioma, visceral splenic lesions and diffuse skeletal lesions. This rare entity is discussed and a brief review of the literature is made.

Angiomatosis quística / Cystic angiomatosis

Se presenta un caso de angiomatosis quística en un paciente que debutó con una tumoración inguinoescrotal debida a una malformación linfangiomatosa retroperitoneal y que presentó así mismo lesiones viscerales esplénicas y lesiones esqueléticas difusas. Se discute esta rara entidad haciendo una revisión de la bibliografía (AU)

[Our experience with aspiration of ectopic ureteroceles]. / Nuestra experiencia con la aspiracion de los ureteroceles ectopicos.

Since 1986 we have performed suction of the ectopic ureteroceles in seven cases. In four of these cases the obstruction caused by the ureteroceles affected the upper hemi-kidney. In the remaining three cases both hemi-kidneys of the same side were affected. One child suffered failure of both hemi-kidneys. All the ureteroceles corresponded to the upper hemi-kidney and were associated with ipsilateral duplicity. In four of the cases the treatment applied was the heminephrectomy of the upper hemi-kidney and the suction of the ureterocele. In one case, we did a nephrectomy and suction of the ureterocele. In the remaining two cases the suction of the ureterocele was done, as well as the ureteropyelostomy, since it was necessary to use the upper hemi-kidney in the renal TC99m dimercaptosuccinic acid scan-DMSA. In five of the children there was a collapse of the ureterocele giving good results in both kidneys. In two of the children there was no collapse, which provoked the need for removal of the ureterocele. In one of these two cases, the renal dilatation persisted later. In the last case it was necessary to perform nephrectomy due to the absence of recuperation of the renal function. Three of the children had associated reflux which disappeared in one of them, after the suction of the ureterocele. Vesical surgery might be avoided by means of the ureterocele's suction technique in 60 per 100 of the cases. However, it is essential to pursue the child's progress once every six months, in order to detect possible failures of ureterocele collapse.

[Bladder calculus formed on chromic suture]. / Cálculo vesical formado sobre sutura crómica.

This is a description of a clinical case of a two-and-a-half year old male child who developed a urinary bladder stone seeded on chromic catgut used to suture of the bladder wall which was damaged in the course of the surgical repair of an inguinal hernia.

[The use of technetium 99m with diethyleneamino pentaacetic acid (Tc 99-DTPA) in the pathology of the pyeloureteral junction]. / Aplicación del tecnecio 99m con ácido dietilenoaminopentacético (Tc 99-DTPA) en la patología de la unión pieloureteral.

By using diuretic renograms with technetium 99m-diethylenetriaminepentaacetic acid (Tc 99-DTPA) as a non-invasive procedure to evaluate paediatric patients with pelvicaliceal dilatation, we are able to make a clear differentiation between dilated, obstructed and non obstructed renal units. This procedure has given us a new insight into the management of these patients, permitting us to decide which patients would benefit from a surgical treatment and which patients would be reserved for clinical observation and follow up.