Nanoparticulated Systems Based on Natural Polymers Loaded with Miconazole Nitrate and Lidocaine for the Treatment of Topical Candidiasis.

People with weakened immune systems are at risk of developing candidiasis which is a fungal infection caused by several species of Candida genus. In this work, polymeric nanoparticles containing miconazole nitrate and the anesthetic lidocaine clorhydrate were developed. Miconazole was chosen as a typical drug to treat buccopharyngeal candidiasis whereas lidocaine may be useful in the management of the pain burning, and pruritus caused by the infection. Nanoparticles were synthesized using chitosan and gelatin at different ratios ranging from 10:90 to 90:10. The nano-systems presented nanometric size (between 80 and 300 nm in water; with polydispersion index ranging from 0.120 to 0.596), and positive Z potential (between 20.11 and 37.12 mV). The determined encapsulation efficiency ranges from 65 to 99% or 34 to 91% for miconazole nitrate and lidocaine clorhydrate, respectively. X-ray diffraction and DSC analysis suggested that both drugs were in amorphous state in the nanoparticles. Finally, the systems fitted best the Korsmeyer-Peppas model showing that the release from the nanoparticles was through diffusion allowing a sustained release of both drugs and prolonged the activity of miconazole nitrate over time against Candida albicans for at least 24 h.

Composite Microparticles Based on Natural Mucoadhesive Polymers with Promising Structural Properties to Protect and Improve the Antifungal Activity of Miconazole Nitrate.

Oropharyngeal candidiasis is a recurrent oral infection caused by Candida species. Gel formulation containing miconazole nitrate is the most common approach for treating oral candidiasis. However, traditional oral topical antifungal therapies have many limitations, including short contact time with the oral mucosa and the necessity to administrate various doses per day. Thus, the aim of this work was to formulate composited microparticulated systems based on combinations of mucoadhesive cationic, anionic, and nonionic polymers that could protect and modify the drug release rate and therefore avoid a fast dilution of the drug by saliva. Microparticulated systems were prepared by the spray drying method employing chitosan, gelatin, and hydroxypropyl methylcellulose. The morphology of the systems was investigated by scanning electron microscopy; drug crystallinity was studied by X-ray, while interactions between polymers were analyzed by infrared spectroscopy. Drug release and halo zone test were employed to analyze the release and activity of the systems loaded with miconazole against Candida albicans cultures. The most appropriate microparticulated system was the one based on chitosan and gelatin which showed homogeneous morphology (mean size of 1.7 ± 0.5 µm), a protective effect of the drug, and better antifungal effect against Candida culture than miconazole nitrate and the other assayed systems. Taking into account these results, this approach should be seriously considered for further evaluation of its safety and in vivo efficacy to be considered as an alternative therapeutic system for the treatment of oral candidiasis.

Succinyl-ß-cyclodextrin: Influence of the substitution degree on albendazole inclusion complexes probed by NMR.

Succinyl-ß-CD derivatives were obtained by green synthesis with degrees of substitution (DS) 1.3 and 2.9. The spray-drying technique was used to obtain albendazole (ABZ):succinyl-ß-CD inclusion complexes. Phase solubility diagrams indicated that both succinyl-ß-CD derivatives formed 1:1 molar ratio ABZ complexes, but the complex with DS 2.9 has a lower formation constant. The presence of stable inclusion complexes in aqueous solution was confirmed by NMR. For both complexes the aromatic moiety is encapsulated into the host cavity. In the solid-state, 13C and 15N NMR spectral differences between ABZ and ABZ included in spray-dried systems showed that strong structural changes occurred in the systems. At least two different ABZ amorphous species were identified based on DS. ABZ species were stable over more than six months based on spectral data. Finally, the influence of DS in the number and type of the inclusion complexes was elucidated.

Effect of drug incorporation technique and polymer combination on the performance of biopolymeric antifungal buccal films.

Numerous films with a dissolved or dispersed active principle within a polymeric matrix have been described in literature. However, the incorporation of solid crystals into the films may influence several relevant properties. Additionally, it has been reported that different polymeric matrices lead to films presenting a different performance. The aim of this work was to evaluate the effect of the combination of chitosan with carrageenan (κ-, λ-, and ι-) as matrices, and of the miconazole nitrate incorporation method, on the films behavior. Mechanical properties, drug release and antifungal activity were evaluated. The state of the drug in the films was analyzed by different techniques. Films showed a homogeneous surface and a thermal protective effect on the drug. The combination of chitosan and λ-carrageenan leads to films with the highest values of tensile and mucoadhesive strength. Films with solubilized drug displayed slightly higher elongation at break, tensile and mucoadhesive strength and faster drug release than those with suspended miconazole nitrate. However, no differences were found regarding the antifungal activity of the different formulations including time-to-kill curves.

Formulation and in-vitro efficacy of antifungal mucoadhesive polymeric matrices for the delivery of miconazole nitrate.

Oral candidiasis is the most common opportunistic infection affecting patients with the human immunodeficiency virus. Miconazole buccal tablets or miconazole gel are approved for the treatment of oropharyngeal candidiasis. However, buccal films present more flexibility and also offer protection for the wounded mucosa, reducing pain. Due to their small size and thickness, buccal films may improve patients' compliance, compared to tablets. Additionally, they may increase the relatively short residence time on the mucosa of oral gels, which are easily removed by saliva. Polymeric films loaded with miconazole nitrate were prepared by a casting/solvent evaporation methodology using chitosan, carbopol, gelatin, gum arabic, and alginate to form the polymeric matrices. The morphology of films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity by differential thermal analysis and X-ray diffraction. Films were characterized in terms of thickness, folding endurance, tensile properties, swelling, adhesiveness, and drug release. Finally, the antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. The more appropriate formulations were those based on chitosan-gelatin and chitosan-carbopol which showed good mechanical properties and adhesiveness, a relative low swelling index, improved drug release, and showed better in vitro activity against Candida cultures than miconazole nitrate raw material. Thus, it will be possible to produce a new pharmaceutical form based on polymeric films containing chitosan and miconazole nitrate, which could be loaded with low drug concentration producing the same therapeutic effect against Candida cultures.

Chondrocytes extract from patients with osteoarthritis induces chondrogenesis in infrapatellar fat pad-derived stem cells.

OBJECTIVE: Infrapatellar fat pad of patients with osteoarthritis (OA) contains multipotent and highly clonogenic adipose-derived stem cells that can be isolated by low invasive methods. Moreover, nuclear and cytoplasmic cellular extracts have been showed to be effective in induction of cell differentiation and reprogramming. The aim of this study was to induce chondrogenic differentiation of autologous mesenchymal stem cells (MSCs) obtained from infrapatellar fat pad (IFPSCs) of patients with OA using cellular extracts-based transdifferentiation method. DESIGN: IFPSCs and chondrocytes were isolated and characterized by flow cytometry. IFPSCs were permeabilized with Streptolysin O and then exposed to a cell extract obtained from chondrocytes. Then, IFPSCs were cultured for 2 weeks and chondrogenesis was evaluated by morphologic and ultrastructural observations, immunologic detection, gene expression analysis and growth on 3-D poly (dl-lactic-co-glycolic acid) (PLGA) scaffolds. RESULTS: After isolation, both chondrocytes and IFPSCs displayed similar expression of MSCs surface makers. Collagen II was highly expressed in chondrocytes and showed a basal expression in IFPSCs. Cells exposed to chondrocyte extracts acquired a characteristic morphological and ultrastructural chondrocyte phenotype that was confirmed by the increased proteoglycan formation and enhanced collagen II immunostaining. Moreover, chondrocyte extracts induced an increase in mRNA expression of chondrogenic genes such as Sox9, L-Sox5, Sox6 and Col2a1. Interestingly, chondrocytes, IFPSCs and transdifferentiated IFPSCs were able to grow, expand and produce extracellular matrix (ECM) on 3D PLGA scaffolds. CONCLUSIONS: We demonstrate for the first time that extracts obtained from chondrocytes of osteoarthritic knees promote chondrogenic differentiation of autologous IFPSCs. Moreover, combination of transdifferentiated IFPSCs with biodegradable PLGA 3D scaffolds can serve as an efficient system for the maintenance and maturation of cartilage tissue. These findings suggest its usefulness to repair articular surface in OA.

[Ability of leukocyte reduction filters to remove fat particles from blood in experimental models simulating blood salvage in orthopedic surgery]. / Capacidad de los filtros leucorreductores para la eliminación de partículas de grasa en sangre. Modelo experimental de simulación de la sangre recuperada en cirugía ortopédica.

BACKGROUND: Salvaged autologous blood in orthopedic surgery may contain tissular debris such as fat particles (FP), possibly increasing the risk of fat embolism after bone surgery. Therefore, this study was initiated to ascertain the capacity of leukocyte filters to remove FP using in vitro models. METHODS: All experiments were performed in triplicate using donor blood bags within 15 days of their donation. Five different olive oil volumes were added to blood to obtain 5 oil concentrations (1% to 5%), and blood was subsequently filtered through a PureCell (Pall Biomedical, Portsmouth, UK) leukocyte-reduction filter. In another set of experiments, 5 different oil volumes (1, 2.5, 5, 7.5 or 10 mL) were injected into the line during filtration of oil-free blood. In addition, 3 preparations of blood supplemented with 5% oil were processed in the autotransfusion device OrthoPAT (Haemonetics Corp, Braintree, MA, USA), and the obtained red cell concentrate was subsequently filtered through PureCell. We collected samples for cell counting and analysis and FP detection with a Pentra 120 Retic (ABX, Montpellier, France) flow cytometer. RESULTS: Specific signals corresponding to FP were clearly detected in the white blood cell scattergrams yielded by the cytometer for oil supplemented blood. PureCell removed FP up to an oil concentration of 3% or up to an injected oil volume of less than 10 mL. Addition of a filtration step through a PureCell filter after blood washing by the OrthoPAT device completely removed FP. CONCLUSIONS: Leukocyte filters seem to be useful for removing FP from unprocessed blood with a low degree of fat contamination (less than 10 mL) and to complete FP removal from processed blood. Therefore, using a leukocyte filter in the patient's line should contribute to improving the safety of perioperative autologous blood salvage.

Evaluación de normas de buenas prácticas de fabricación de mezclas de nutrición parenteral extemporánea / Evaluation of good standars practices of fabrication parenteral nutrition extemporaneous mixtures

Las buenas prácticas de fabricación (BPF) sistematizan un conjunto de recomendaciones cuya aplicación es, sin lugar a dudas el camino más eficaz para asegurar la calidad de los productos farmacéuticos. Su finalidad es doble: por un lado, proveer a la industria farmacéutica de una referencia para la evaluación y aplicación de procedimientos de fabricación adecuados, y por el otro, faciliar las tareas de fiscalización y control de las autoridades sanitarias, así como la armonización de las respectivas normativas nacionales. Las normas nacionales de BPF ofrecen un marco regulatorio para asegurar que las mezclas de nutrición parenteral extemporáneas preparadas sean adecuadas para el fin propuesto, garantizando que cumplan con los requisitos de calidad, seguridad, pureza y eficacia preestablecidos, así como también presentar evidencia documentada completa del cumplimiento de las buenas practicas de fabricación...

Evaluación de normas de buenas prácticas de fabricación de mezclas de nutrición parenteral extemporánea / Evaluation of good standars practices of fabrication parenteral nutrition extemporaneous mixtures

Las buenas prácticas de fabricación (BPF) sistematizan un conjunto de recomendaciones cuya aplicación es, sin lugar a dudas el camino más eficaz para asegurar la calidad de los productos farmacéuticos. Su finalidad es doble: por un lado, proveer a la industria farmacéutica de una referencia para la evaluación y aplicación de procedimientos de fabricación adecuados, y por el otro, faciliar las tareas de fiscalización y control de las autoridades sanitarias, así como la armonización de las respectivas normativas nacionales. Las normas nacionales de BPF ofrecen un marco regulatorio para asegurar que las mezclas de nutrición parenteral extemporáneas preparadas sean adecuadas para el fin propuesto, garantizando que cumplan con los requisitos de calidad, seguridad, pureza y eficacia preestablecidos, así como también presentar evidencia documentada completa del cumplimiento de las buenas practicas de fabricación...(AU)

Calcium alginate microspheres of Bacillus subtilis.

Microspheres of Bacillus subtilis were prepared using sodium alginate. Some typical properties of microencapsulated systems, such as microorganism content, particle size, and germination time, were studied. Calcium alginate microspheres were obtained by the emulsification method, dripping into a solution of calcium salt. The conditions of the preparation steps were very soft to produce calcium alginate microspheres containing cells with no apparent changes in general biological properties. The hydrogel matrix provides protection without preventing communication with the surrounding medium.

Deformidade angular do rádio e da ulna tratada pela distraçäo osteogênica percutânea dinâmica: relato de Caso / Angular deformation of radius and ulna treated by dynamic percutaneus osteogenesis distraction: case report

O exame de um cäo de quatro meses de idade, macho, sem raça definida, com peso de 5,7kg mostrou que ele se apoiava com os cotovelos e apresentava desvio acentuado bilateral do rádio e da ulna. Ao exame radiográfico, observou-se fratura proximal bilateral do rádio. Após avaliaçöes clínica e radiológica foi indicada a osteotomia corretiva e distraçäo osteogênica do membro anterior esquerdo. O procedimento cirúrgico constou de osteotomia na diáfise proximal do rádio e ulna e emprego de fixadores externos compostos por quatro pinos de Kirschner e duas barras metálicas rosqueadas, configurando um fixador tipo II, bilateral uniplanar dinâmico. Antes da fixaçäo dos pinos com acrílico, os fragmentos ósseos fraturados foram separados em aproximadamente 0,5cm. Após 10 dias, iniciou-se a distraçäo de 1,0mm/dia durante 30 dias. A consolidaçäo da fratura foi observada radiograficamente aos 67 dias após a intervençäo, quando o aparelho foi removido. Procedimento semelhante foi realizado no membro anterior direito, quando o animal se encontrava com 16 meses de idade. Foi necessária a retirada de uma cunha óssea de aproximadamente 1,0cm para a correçäo angular. Atualmente, o cäo mostra apoio normal do membro anterior esquerdo e discreto desvio valgus do direito devido à quebra do implante

Microesferas de alginato con Bacillus subtilis / Alginate microspheres of Bacillus subtilis

La microencapsulación de organismos ha sido considerada como una alternativa de inmovilización de células, a fin de que éstas puedan ejercer sus funciones en forma gradual. El objetivo del presente estudio fue elaborar microesferas de Bacillus subtilis ya sea en forma esporulada como vegetativa.Microesferas de Bacillus subtilis son preparadas utilizando alginato de sodio. Algunas propiedades típicas del sistema microencapsulado, tales como contenido de microorganismos, tamaño de partícula y tiempo de germinación han sido estudiados. Las microesferas se prepararon mediante el método de coaservación-separación de fases, utilizando una etapa intermedia de emulsión múltiple. Las condiciones de preparación han sido lo suficientemente benignas para no producir cambios en las propiedades biológicas generales del sistema, pero con la protección que le otorga la matriz del hidrogel, la cual evita la directa comunicación con el medio externo.La viabilidad demostrada por las microesferas con las formas esporuladas fue significativamente superior a las de las formas vegetativas (AU)

[Production and characterization of an atenolol-reticulated povodone tablet]. / Obtención y caracterización de un complejo de atenolol con povidona reticulada.

The production of polymeric complexes in many active drugs with reticulated povidone increased dissolved component percentage. In this work made use a coevaporation technique. Complex formation has been tested by X Ray Diffractometry and Differential Scanning Calorimetry. The percentage of dissolution was determined to the USP XXIII Edition methodology. As can be seen from the results, the Atenolol-reticulated Povidone complexes has greater solubility than the Atenolol mixed with Lactose as excipient.

[The diffusion and dissolution of metronidazole and doxepin in semisolid pharmaceutical forms through synthetic membranes]. / Estudio de difusión y disolución de metronidazol y doxepina en formas farmacéuticas semisolidas a través de membranas sintéticas.

The dissolution and diffussion methods through homogeneous synthetic membrane were studied in different semisolid topical formulations containing metronidazole and doxepin. The results suggest that the rate of release showed a first order kinetic for one of the formulations and the rate of release described by Higuchi for the others.

[Determination of serum ferritin: ideas for avoiding induced ferropenia in blood donors]. / Determinación de ferritina sérica: consideraciones para evitar ferropenia inducida en donantes de sangre.

PURPOSE: To evaluate blood donation as a cause of iron deficiency. MATERIAL AND METHODS: Serum ferritin levels were determined by enzymoimmunoassay with an SRItm autoanalyser in 500 blood donors of both sexes chosen at random and in 200 suitors for blood donation, used as control group. Iron deficiency was defined by ferritin values below 15 ng/dL. Age, sex, total number of blood donations and those carried out in the last year were all correlated for the statistical analysis, performed with the SPSS/PC+ pack. RESULTS: The mean ferritin value in men was 86.0 ng/dL, and in women this was 27.1 ng/dL. With respect to the control group, blood donors showed increased iron deficiency, 7.4% for men and 11.8% for women. Highly significant direct correlation was found in male donors between total donations, last-year donations and age, and between total number of donations and age in female donors; highly significant inverse correlation was found between total number of donations, last-year donations and ferritin levels among the male donors, while these correlations lacked significance in the female donors. When correlating last-year donations with mean ferritin levels in women, low, although constant, ferritin values were seen, whereas a marked descent was found in men. Iron deficiency was strikingly spread among women, ranging between 21% of those with one blood donation to 46% in those with 4 donations during the last year; in men, iron deficiency was present in 14% of those with 4 or more blood donations in the last year. With respect to total number of blood donations and mean ferritin values, iron deficiency was found in 50% of the women with 8 donations and in 12.8% of men with 14 donations. Ferritin levels decrease in blood donors with aging beyond two blood donations in both sexes. CONCLUSIONS: 1st) Iron deficiency related to blood donation is demonstrated. This deficiency is clearly seen in men after the first blood donations and is more intense in women, as their previous reserves are lower. 2nd) Ferritin is the best marker for estimating iron deposits, and enzymoimmunoassay is the technique of choice as it seems easy to perform and is automatic. 3rd) Determining ferritin levels in the first blood donation seems advisable in order to assess previous deposits and to evaluate yearly the state or iron reserves. 4th) Iron supplement is advisable during the 4 first donations in regular blood donors and in those with iron deficiency, with ferrous sulphate at a dose of 100 mg/day for 10 days.

Serum penicillin concentrations after intramuscular administration of benzathine penicillin G in children with rheumatic fever and controls.

Serum and urine penicillin levels were determined in 11 children with rheumatic fever (RF) who were receiving benzathine penicillin G (BPG) prophylactically every 3 weeks and in 10 children without RF who received the drug for the treatment of other infections. The dose given was 600,000 units for children weighing less than 25 kg and 1,200,000 units for those with a weight above 25 kg. Blood and urine samples were collected from both groups before and on days 7, 14 and 21 after BPG administration. Our results showed that: minimum inhibitory concentrations (MICs) of BPG for group A beta-hemolytic streptococci were 0.02 IU/ml or 0.0125 microgram/ml; intramuscular BPG did not give adequate serum levels to block the growth of group A beta-hemolytic streptococci in approximately 24 and 62% of children included in the study on days 14 and 21 after its administration, respectively; BPG metabolism was similar in both groups and did not depend on the underlying disease; serum and urine levels did not vary according to sex and weight; and there was a small correlation between serum and urine levels.