RESUMEN

BACKGROUND: Nanoparticles (NPs) incorporating drug formulations can be used to facilitate passage through biological barriers including the blood-brain barrier (BBB) and increase drug delivery and bioavailability. Hence, NP-based administration may enhance the efficiency of current antipsychotics. Encapsulation within NPs can resolve aqueous solubility problems that not only reduce permeability through the BBB but also affect targeting. The present study describes a new drug delivery system based on proteinoid NPs to explore the possibility of improving drug efficacy. Risperidone (RSP) is a commonly used atypical antipsychotic medication, and was therefore selected for encapsulation by proteinoid NPs. RESULTS: Proteinoid polymers with high molecular weight and low polydispersity were synthesized from L-amino acids and poly-L-lactic acid (PLLA) by thermal step-growth polymerization mechanism. RSP-loaded proteinoid NPs were then prepared using a self-assembly process in the presence of RSP, followed by PEGylation. The optimal PEGylated RSP-loaded NPs were characterized in terms of diameter and size distribution, drug loading, ζ-potential, cytotoxicity, biodistribution, and psychopharmacological effects. The findings indicate significantly higher antipsychotic activity of drug-loaded proteinoid NPs compared to free RSP. CONCLUSIONS: Proteinoid NPs enhance RSP delivery and may potentially increase drug efficiency by reducing dosage and side effects.

Asunto(s)

RESUMEN

This study presents a new process for hydrophilic formulation of liquid oils, by encapsulation and solidification of the oils within porous hollow silica microspheres of narrow size distribution. Jojoba [Simmondsia chinensis] oil was chosen as a model study due to its broad potential applications. Jojoba oil is produced from the seeds of the jojoba plant, which are rich in liquid wax. Today, jojoba oil is mainly used for applications such as pharmaceuticals and cosmetics. The oil is primarily used as a carrier oil that stabilizes sensitive active compounds, such as vitamins and other oils, which are susceptible to air oxidation or UV-light degradation. Silica (SiO2) particles are used in many different industrial products such as food and cosmetics due to their chemical inertness. Here, uniform porous hollow SiO2 microspheres, composed of sintered SiO2 nanoparticles, were made by coating polystyrene template microspheres of narrow size distribution with three layers of SiO2 nanoparticles, followed by removal of the polystyrene core by combustion at 500 °C. The synthesis stages were characterized by SEM, TEM, FTIR and TGA analyses. The measurements confirmed the increasing content of SiO2 after each coating cycle and the absence of polystyrene in the final hollow particles. Jojoba oil was successfully encapsulated within the hollow SiO2 microspheres by heating/cooling cycles, reaching an encapsulation yield of up to 10 times of the SiO2 dry shell weight. The oil encapsulation was confirmed by a floatability test and confocal microscopy. The hollow SiO2 and the oil-filled microspheres were found non-toxic to HaCaT cell line, a spontaneously transformed human epithelial cell line from adult skin. Furthermore, the oil-filled SiO2 microspheres were dispersed in a hydrogel and exhibited a homogeneous water-based formulation that appeared stable after six months storage. In light of these findings, we offer these jojoba oil-filled particles as a model for hydrophilic formulation of oils in general and in particular as suitable candidates for pharmaceutical and cosmetic applications.

Asunto(s)

RESUMEN

BACKGROUND: Most primary and metastatic bone tumors demonstrate increased osteoclast activity and bone resorption. Current treatment is based on a combination of surgery, radiotherapy and chemotherapy. Severe side effects are associated with chemotherapy due to use of high dosage and nonspecific uptake. Bisphosphonates have a strong affinity to Ca2+ ions and are widely used in the treatment of bone disorders. RESULTS: We have engineered a unique biodegradable bisphosphonate nanoparticle (NPs) bearing two functional surface groups: (1) primary amine groups for covalent attachment of a dye/drug (e.g. NIR dye Cy 7 or doxorubicin); (2) bisphosphonate groups for targeting and chelation to bone hydroxyapatite. In addition, these engineered NPs contain high polyethyleneglycol (PEG) concentration in order to increase their blood half life time. In vitro experiments on Saos-2 human osteosarcoma cell line, demonstrated that at a tenth of the concentration, doxorubicin-conjugated bisphosphonate NPs achieved a similar uptake to free doxorubicin. In vivo targeting experiments using the NIR fluorescence bisphosphonate NPs on both Soas-2 human osteosarcoma xenograft mouse model and orthotopic bone metastases mCherry-labeled 4T1 breast cancer mouse model confirmed specific targeting. In addition, therapeutic in vivo experiments using doxorubicin-conjugated bisphosphonate NPs demonstrated a 40% greater inhibition of tumor growth in Saos-2 human osteosarcoma xenograft mouse model when compared to free doxorubicin. CONCLUSIONS: In this research we have shown the potential use of doxorubicin-conjugated BP NPs for the targeting and treatment of primary and metastatic bone tumors. The targeted delivery of doxorubicin to the tumor significantly increased the efficacy of the anti-cancer drug, thus enabling the effective use of a lower concentration of doxorubicin. Furthermore, the targeting ability of the BP NPs in an orthotopic xenograft mouse model reinforced our findings that these BP NPs have the potential to be used for the treatment of primary and metastatic bone cancer.

Asunto(s)

RESUMEN

Bisphosphonate (BP) compounds are widely used in the treatment of bone disorders. This group of drugs with a high affinity to Ca(+2) ions is rapidly attracted to bone mineral, especially in areas of high resorption. We have engineered unique biodegradable BP nanoparticles (NPs) by dispersion co-polymerization of the monomers methacrylate-PEG-BP) and (3-Aminopropyl)mathacrylamide) with the crosslinker monomer tetra ethylene glycol diacrylate. These NPs possess a dual functionality: (1) covalent attachment of a dye (e.g. near IR dye) or a drug to the nanoparticles through the primary amine groups on the surface of the NPs; (2) chelation to the bone mineral hydroxyapatite through the BP on the surface of the NPs. This study describes the uptake of the unique near IR fluorescent Cy 7-conjugated BP NPs in bone of a young mouse model. Blood half-life studies revealed a relatively long half-life (approximately 5 h) due to a high concentration of PEG in the BP NPs as well as a relatively long whole body clearance (approximately 2 weeks). Body distribution studies showed a specific uptake of the BP NPs in bone. These unique engineered BP NPs are planned to be utilized in future work for diagnostic and drug delivery systems that are targeted to bone disorders.

Asunto(s)

RESUMEN

Using in situ high-resolution synchrotron x-ray scattering, the Curie temperature TC has been determined for ultrathin c-axis epitaxial PbTiO3 films on conducting substrates (SrRuO3 on SrTiO3), with surfaces exposed to a controlled vapor environment. The suppression of TC was relatively small, even for the thinnest film (1.2 nm). We observe that 180 degrees stripe domains do not form, indicating that the depolarizing field is compensated by free charge at both interfaces. This is confirmed by ab initio calculations that find polar ground states in the presence of ionic adsorbates.

RESUMEN

The human ZIC gene family is comprised of five members encoding zinc-finger transcription factors, which are the vertebrate homologs of the Drosophila odd-paired gene. Mutations in ZIC genes in humans have recently been implicated in a wide variety of congenital malformations, including Dandy-Walker malformation, holoprosencephaly, neural tube defects, and heterotaxy. Mutant analysis of these genes in mice has underscored the conserved developmental roles of these genes. Further, this analysis has begun to elucidate the molecular and developmental mechanisms underlying these important birth defects.

Asunto(s)

RESUMEN

We report the case of a patient who was found to have an aorto-right ventricular fistula 17 years after receiving a Björk-Shiley prosthetic aortic valve. A pseudoaneurysm had formed at the aortotomy suture line, and it had extended into the interventricular septum and had eventually opened into the right ventricle. Using transesophageal echocardiography, we identified the defect in the ascending aorta, and a left-to-right shunt. Aortography was used to confirm these findings. The pseudoaneurysm was successfully resected and the ascending aorta was replaced with a Dacron graft. To the best of our knowledge, no similar late complication of aortic valve replacement has been reported in the medical literature.

Asunto(s)

RESUMEN

The pathogenic agent, adenovirus (Ad), has taken on a new role as a vector for gene transfer in both laboratory and clinical settings. To help understand the intracellular pathways and fate of Ad gene transfer vectors, we covalently conjugated fluorophores to E1-, E3- Ad vectors and used quantitative fluorescence microscopy to assess essential steps of Ad vector gene transfer to the A549 human epithelial lung cell line including binding, internalization, escape from endosomes, translocation to the nucleus, dissociation of capsids and gene expression. The data demonstrate that Ad internalizes with a t1/2 2.5 min, breaks out of endosomes early, likely prior to endosome-endosome fusion, exhibits sustained, intracellular velocities averaging 0.58 microm/sec, and translocates to the nucleus with >80% of internalized fluorophore demonstrating nuclear localization within 60 min of infection. Interestingly, 24 hr after infection, half of the initially internalized fluorescence was detected but lacked nuclear localization, suggesting that the capsid is released from the nucleus and is likely degraded. Fluorescent labeling of virions provides a novel quantitative, morphological strategy to characterize the interaction of gene transfer vectors with the intracellular environment.

Asunto(s)

RESUMEN

Spontaneous echocardiographic contrast (SEC) is an occasional finding observed in the atria in patients undergoing transesophageal echocardiographic studies, but has rarely been described in the descending thoracic aorta in the absence of an aortic dissection. The pathophysiology of SEC in the cardiac and vascular structures appears to be related to an interaction between red blood cells and plasma proteins in the setting of a low flow state. In this report we present three cases of SEC in the descending thoracic aorta, with one of the cases of SEC resolving with repair of his underlying cardiac disorder.

Asunto(s)

RESUMEN

A case of hemochromatosis--a disease in which iron is deposited in parenchymatous organs in the form of hemosiderin leading to fibrosis and functional impairment of these organs--is reported. The classical triad of symptoms seen in hemochromatosis (cirrhosis of the liver, diabetes mellitus, and skin pigmentation) are often supplemented by cardiomyopathy. In this case, postmortem examination revealed pigmentary cirrhosis of the liver and pancreas and hemosiderin deposits in the myocardium and other organs. The leading cause of death was concluded to be hemochromatosis of the heart.

Asunto(s)

RESUMEN

Sensitivity to 10 antibiotics of 1074 strains of opportunistic enterobacteria isolated from 117 children at the age of 2 years was studied (57 healthy children and 60 children with salmonellosis). The structure of the conjugative drug resistance of the opportunistic enterobacteria, the frequency of their isolation and the spectrum correlating with multiple resistance of the strains to 4-10 antibiotics were shown. The frequency of the conjugative determinants of the antibiotics resistance in the opportunistic bacteria isolated from the patients with salmonellosis was higher. The structure of the conjugative drug resistance of the opportunistic enterobacteria in the dynamics of the salmonellosis process was close to the transmissive R-plasmid resistance of S. typhimurium.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)