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Alejandro Sánchez

Publications and source records attributed to Alejandro Sánchez.

11 recordsLinked to original sources
PubMed2006

Twenty-four-hour ambulatory oximetry monitoring in COPD patients with moderate hypoxemia.

BACKGROUND: The relationship of diurnal desaturations (oximetry-measured blood oxygen saturation [S(pO(2))] < 90%) during activities of daily living and clinical aspects in patients with chronic obstructive pulmonary disease (COPD) and moderate hypoxemia has not been systematically evaluated. METHODS: We prospectively studied 88 patients with stable COPD (forced expiratory volume in the first second [FEV(1)] < 80% of predicted, ratio of FEV(1) to forced vital capacity < 70% of predicted, and P(aO(2)) 60-70 mm Hg) with 24 hours of ambulatory oximetry. Desaturators were defined as those who spent >/= 30% of the time with S(pO(2)) < 90%. Patients engaged in their usual activities of daily living. We correlated these desaturations with the following variables, measured immediately before the 24 hours of oximetry: body mass index, dyspnea (measured with the modified Medical Research Council dyspnea scale), gas exchange, pulmonary function, quality of life (measured with the Saint George's respiratory questionnaire), and comorbidity (measured with the Charlson index). RESULTS: Thirty-three (38%) of the patients were desaturators: 50% nocturnal and 22% diurnal. We also measured daytime arterial blood gas values from arterial blood samples and found that the desaturators had higher P(aCO(2)) (p = 0.001) and lower P(aO(2)) (p = 0.007) than the nondesaturators. There were no differences in the other variables. The correlation between nocturnal and diurnal time with S(pO(2)) < 90% was r(2) = 0.67, and the concordance was low (Cohen's kappa 0.43, p < 0.001). CONCLUSIONS: Patients with stable COPD and moderate hypoxemia have frequent and potentially important desaturations during activities of daily living and at night. In addition, there is a big difference in the profile and degree of nocturnal and diurnal desaturations. Twenty-four hours of oximetry provides valuable information for comprehensive evaluation of patients with COPD.

Activities of Daily Living↗
PubMed2005

Nanoparticles as carriers for nasal vaccine delivery.

At present, there is considerable excitement within the nanotechnology field with regard to the potential use of nanosystems as carriers for mucosal vaccine delivery. Indeed, many of the vaccines available, including protein antigens and DNA vaccines, are very unstable and need to be protected from degradation in the biologic environment. In addition, their efficacy is limited by their poor capacity to cross biologic barriers and reach the target sites. As a consequence, the design of appropriate antigen carriers that could help overcome these problems has become a significant challenge. The goal of the present article is to review the recent advances in the design of polymeric nanosystems intended to be used as carriers for nasal vaccine delivery. More specifically, the authors present nanocarriers that have been made of safe materials, such as biodegradable polyesters and polysaccharides. The information accumulated regarding the in vivo behavior of these nanocarriers indicates that they are able to facilitate the transport of the associated antigen across the nasal epithelium, thus leading to efficient antigen presentation to the immune system. Furthermore, the results suggest that not only the size and surface properties but also the polymer composition and the structural architecture of the nanosystems are critical for the optimization of these antigen carriers. In conclusion, future studies intended to provide increased knowledge regarding these properties and how they relate to the efficiency of the immune responses, will undoubtedly affect the design of new and more effective nasal vaccine delivery strategies.

Administration, Intranasal↗
PubMed2004

Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice.

High molecular weight (Mw) chitosan (CS) solutions have already been proposed as vehicles for nasal immunization. The aim of the present work was to investigate the potential utility of low Mw CS in the form of nanoparticles as new long-term nasal vaccine delivery vehicles. For this purpose, CS of low Mws (23 and 38 kDa) was obtained previously by a depolymerization process of the commercially available CS (70 kDa). Tetanus toxoid (TT), used as a model antigen, was entrapped within CS nanoparticles by an ionic cross-linking technique. TT-loaded nanoparticles were first characterized for their size, electrical charge, loading efficiency and in vitro release of antigenically active toxoid. The nanoparticles were then administered intranasally to conscious mice in order to study their feasibility as vaccine carriers. CS nanoparticles were also labeled with FITC-BSA and their interaction with the rat nasal mucosa examined by confocal laser scanning microcopy (CLSM). Irrespective of the CS Mw, the nanoparticles were in the 350 nm size range, and exhibited a positive electrical charge (+40 mV) and associated TT quite efficiently (loading efficiency: 50-60%). In vitro release studies showed an initial burst followed by an extended release of antigenically active toxoid. Following intranasal administration, TT-loaded nanoparticles elicited an increasing and long-lasting humoral immune response (IgG concentrations) as compared to the fluid vaccine. Similarly, the mucosal response (IgA levels) at 6 months post-administration of TT-loaded CS nanoparticles was significantly higher than that obtained for the fluid vaccine. The CLSM images indicated that CS nanoparticles can cross the nasal epithelia and, hence, transport the associated antigen. Interestingly, the ability of these nanoparticles to provide improved access to the associated antigen to the immune system was not significantly affected by the CS Mw. Indeed, high and long-lasting responses could be obtained using low Mw CS molecules. Furthermore, the response was not influenced by the CS dose (70-200 microg), achieving a significant response for a very low CS dose. In conclusion, nanoparticles made of low Mw CS are promising carriers for nasal vaccine delivery.

Administration, Intranasal↗
PubMed2004

Bacillus subtilis transcriptional regulators interaction.

Bacillus subtilis aprE gene codes for the extracellular protease subtilisin. Its expression is controlled by AbrB, DegU, Hpr, SinI, SinR and Spo0A transition state protein regulators. To determine in vivo the protein-protein interactions among these regulators, we used the LexA-based bacterial genetic two-hybrid system. Our results show homo-dimerization to all the analyzed proteins and hetero-dimerization between SinR-SinI and SinR-Hpr.

Bacillus subtilis↗
PubMed2004

Chitosan nanoparticles as new ocular drug delivery systems: in vitro stability, in vivo fate, and cellular toxicity.

PURPOSE: To assess the potential of chitosan (CS) nanoparticles for ocular drug delivery by investigating their interaction with the ocular mucosa in vivo and also their toxicity in conjunctival cell cultures. METHODS: Fluorescent (CS-fl) nanoparticles were prepared by ionotropic gelation. The stability of the particles in the presence of lysozyme was investigated by determining the size and their interaction with mucin, by measuring the viscosity of the mucin dispersion. The in vivo interaction of CS-fl nanoparticles with the rabbit cornea and conjunctiva was analyzed by spectrofluorimetry and confocal microscopy. Their potential toxicity was assessed in a human conjunctival cell line by determining cell survival and viability. RESULTS: CS-fl nanoparticles were stable upon incubation with lysozyme and did not affect the viscosity of a mucin dispersion. In vivo studies showed that the amounts of CS-fl in cornea and conjunctiva were significantly higher for CS-fl nanoparticles than for a control CS-fl solution, these amounts being fairly constant for up to 24 h. Confocal studies suggest that nanoparticles penetrate into the corneal and conjunctival epithelia. Cell survival at 24 h after incubation with CS nanoparticles was high and the viability of the recovered cells was near 100%. CONCLUSIONS: CS nanoparticles are promising vehicles for ocular drug delivery.

Animals↗
PubMed2003

Biodegradable micro- and nanoparticles as long-term delivery vehicles for interferon-alpha.

The development of new interferon-alpha (IFN-alpha) delivery strategies is a key issue in order to simplify its administration and improve its therapeutic effects, while reducing its dose-related side effects. One of the most attractive approaches towards this aim is the encapsulation of IFN-alpha into poly(lactic-glycolic acid) (PLGA) microspheres. Nevertheless, the stability of IFN-alpha released from these microspheres has been identified as one of the most important concerns in relation to the potential of this approach. Being conscious of this problem, we have used new strategies for the encapsulation of IFN-alpha into biodegradable micro- and nanoparticles. We chose poloxamer 188 as a stabilizing agent and encapsulated IFN-alpha within PLGA/poloxamer blend microspheres prepared by an oil-in-oil solvent extraction technique and also within PLGA micro- and nanospheres containing poloxamer, prepared by the water-in-oil-in-water solvent evaporation technique. The results showed that these techniques led to the efficient encapsulation of IFN-alpha and the modulation of their particle size, ranging from nanospheres (280 nm) to 40 microm-microspheres. These systems exhibit a similar pattern of release that is characterized by an initial burst (2-24% IFN-alpha released, as determined by ELISA) followed by small pulses of immunoenzymatically detected IFN-alpha for up to 1 month. The maintenance of the structural integrity and bioactivity of the protein was confirmed using a cytostasis bioassay. The results showed that the antiproliferative activity of the IFN-alpha varied depending on the formulation. More specifically, PLGA/poloxamer blend microspheres were able to provide significant amounts of active IFN-alpha for up to 96 days. This new IFN-alpha delivery system opens up possibilities to improve present IFN-alpha-based therapies.

Biodegradation, Environmental↗
PubMed2003

The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa.

The influence of the surface characteristics of colloidal drug carriers in their interaction with different biological surfaces is becoming increasingly evident. In order to investigate the importance of these characteristics in their interaction with the ocular mucosa, we developed three types of nanocapsules that differ in their surface properties: poly- epsilon -caprolactone (PECL) nanocapsules, chitosan (CS)-coated PECL nanocapsules and poly(ethylene glycol) (PEG)-coated PECL nanocapsules. Two different approaches were used to form these polymer coated nanocapsules: (i) the electrostatic anchorage of the coating onto the PECL nanocapsules-in the case of CS-and (ii) the use of the previously synthesized copolymer PECL-PEG for the formation of the nanocapsules. In both cases, the systems, prepared by the interfacial deposition technique, were loaded with a fluorescent dye (rhodamine) in order to quantify and visualize their interaction with the ocular surface ex vivo and in vivo. An important conclusion from the ex vivo studies is that the developed systems, and specially the CS-coated ones, enhanced the penetration of the encapsulated dye through the cornea. This effect was not simple due to the physical presence of the nanocapsules but to their ability to carry the encapsulated compound. The second conclusion from the confocal laser scanning microscopy (CLSM) studies is that the systems were able to enter the corneal epithelium by a transcellular pathway and that the penetration rate was dependent on the coating composition. The images suggest that the PEG coating accelerates the transport of the nanocapsules across the whole epithelium, whereas the CS coating favours the retention of the nanocapsules in the superficial layers of the epithelium. The specific behaviour of CS-coated systems was also corroborated in vivo. These results indicate that the surface composition of colloidal drug carriers affects their biodistribution in the eye. Therefore, this surface modification approach can be used as a targeting strategy in ocular drug delivery.

Animals↗
PubMed2003

The potential of chitosan in ocular drug delivery.

This paper presents an overview of the potential of chitosan-based systems for improving the retention and biodistribution of drugs applied topically onto the eye. Besides its low toxicity and good ocular tolerance, chitosan exhibits favourable biological behaviour, such as bioadhesion- and permeability-enhancing properties, and also interesting physico-chemical characteristics, which make it a unique material for the design of ocular drug delivery vehicles. The review summarizes the techniques for the production of chitosan gels, chitosan-coated colloidal systems and chitosan nanoparticles, and describes their mechanism of action upon contact with the ocular mucosa. The results reported until now have provided evidence of the potential of chitosan gels for enhancing and prolonging the retention of drugs on the eye surface. On the other hand, chitosan-based colloidal systems were found to work as transmucosal drug carriers, either facilitating the transport of drugs to the inner eye (chitosan-coated colloidal systems containing indometacin) or their accumulation into the corneal/conjunctival epithelia (chitosan nanoparticles containing ciclosporin). Finally, the tolerance, toxicity and biodegradation of the carriers under evaluation were reviewed.

Administration, Topical↗
PubMed2002

Efficacy and safety of microspheres of cyclosporin A, a new systemic formulation, to prevent corneal graft rejection in rats.

PURPOSE: To evaluate the efficacy and safety of a new systemic formulation of cyclosporin A (CsA)-loaded microspheres in a rat model of penetrating keratoplasty rejection. METHODS: Female Lewis rats received orthotopic corneal allografts from inbred female Fisher donors. The rats were divided into three groups: 1, untreated controls; 2, daily subcutaneous injection of 10 mg/kg of the commercially intravenous CsA formulation starting after surgery (time 0) and for 15 days; and 3, one subcutaneous injection of 150 mg/kg of CsA microspheres. The grafts were evaluated clinically for 30 days and the rejection index, mean survival time, and rejection rate were calculated. Serum levels of CsA were measured at 5, 10, 15, 20, and 30 days in groups 2 and 3. Eyes, liver, and kidneys were histologically evaluated at the end of the experiment. RESULTS: Graft rejection was significantly reduced in group 3 at day 30 (P < 0.05) and serum levels of CsA were constant (range, 73.28 +/- 43.93 to 183.33 +/- 83.69 ng/ml). High levels (>3000 ng/ml) were obtained in group 2 as long as CsA was injected. Both formulations delayed rejection onset, but only the microspheres decreased the rate of corneal graft rejection (100% in group 2 and 70% in group 3 at day 30). Histologic examination showed no hepatic lesions with either formulation, but both resulted in deposition of a hemoglobin-like material in the kidneys. CONCLUSIONS: Although subcutaneous CsA-loaded microspheres delay rejection onset and decrease the rate of corneal graft rejection in an orthotopic keratoplasty rejection model in rats, administration of the microspheres did not prevent acute renal toxicity.

Animals↗
PubMedDate not supplied

PLGA:poloxamer and PLGA:poloxamine blend nanoparticles: new carriers for gene delivery.

The main objective of the present work was the development of new nanoparticulate carrier systems for the delivery of plasmid DNA. These new carriers consist of a blend matrix formed by a poly(lactic-co-glycolic acid) (PLGA) copolymer and polyoxyethylene derivatives. More specifically, we have prepared nanostructures with different PLGA:poloxamer and PLGA:poloxamine compositions by an optimized emulsification-solvent diffusion technique and studied the potential of these carriers for the encapsulation and controlled release of plasmid DNA. Depending on the particle composition, the encapsulation efficiency of the model plasmid pEGFP-C1 varied between 30% and 45%. All formulations provided continuous and controlled release of the plasmid with minimal burst effect. In addition, the release rate and duration was dependent on the composition of the particle matrix. Moreover, gel electrophoresis and cell culture (MCF-7 cell line) assays allowed us to confirm that the biologically active form of the plasmid was preserved during the particle preparation process and also during its release. Cell culture experiments also indicated that the new nanoparticles do not exhibit toxic effects on these cells at concentrations up to 5 mg/mL. Altogether, these results indicate that these composite nanostructures present a promising approach for the delivery of plasmid DNA.

Cell Line, Tumor↗