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.

Prevalence and caries-related risk factors in schoolchildren of 12- and 15-year-old: a cross-sectional study.

BACKGROUND: To assess the prevalence and severity of caries in 12- and 15-year-old schoolchildren, and to analyse the related risk factors. METHODS: We conducted a cross-sectional study on a random sample of 1843 schoolchildren aged 12 and 15 from Galicia (northwest of Spain). Self-administered questionnaire and dental clinical examination were performed to obtain information about oral health habits, dental caries and oral hygiene. A logistic regression model including dental-caries-related variables was generated for each age group. RESULTS: The respective findings for 12- and 15-years-old were as follows: decayed, missing, filled teeth index both for permanent and temporary dentition (DMFT/dmft) of 0.89 (95% CI, 0.87-0.91) and 1.38 (95% CI, 1.33-1.43), respectively; caries prevalence 39.6% (95% CI, 36.3-42.9) and 51.7% (95% CI, 48.0-55.4), respectively. In the 12-year-old group, individuals who occasionally, never or hardly ever brushed their teeth had higher values of caries (OR = 1.83, 95% CI 1.07-3.15, and OR = 9.14, 95% CI1.63-51.17, respectively). Also, the presence of plaque on more than 1/3 gingival was statistically associated with an increase of caries (OR = 2.03; 95% CI, 1.11-3.70), and living in a rural environment was a risk factor (OR = 1.3; 95% CI,1.02-1.80). In the 15-year-old group, higher caries risk was found when brushing was performed once a day (OR = 1.61; 95% CI,1.03-2.50), and among individuals who visited private clinics (OR = 1.77; 95% CI, 1.17-2.66), while electric toothbrush was associated with a lower caries risk (OR = 0.50; 95% CI, 0.29-0.86). CONCLUSIONS: This study revealed that risk factors of dental caries showed differences in schoolchildren of 12- and 15-year-old. Strongest evidence related to caries in 12-year-old group were found in frequency of toothbrushing and dental plaque. In 15-year old group, electric toothbrush, time since the last visit to the dentist and type of dental care (public/private) had a stronger association with dental caries. Caries prevalence and mean DMFT/dmft increased from 12- to 15-year-old, in spite of improvement in oral hygiene at the age of 15.

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.

Bioactive lipids are altered in the kidney of chronic undernourished rats: is there any correlation with the progression of prevalent nephropathies?

BACKGROUND: Undernutrition during childhood leads to chronic diseases in adult life including hypertension, diabetes and chronic kidney disease. Here we explore the hypothesis that physiological alterations in the bioactive lipids pattern within kidney tissue might be involved in the progression of chronic kidney disease. METHODS: Membrane fractions from kidney homogenates of undernourished rats (RBD) were submitted to lipid extraction and analysis by thin layer chromatography and cholesterol determination. RESULTS: Kidneys from RBD rats had 25% lower cholesterol content, which disturb membrane microdomains, affecting Ca2+ homeostasis and the enzymes responsible for important lipid mediators such as phosphatidylinositol-4 kinase, sphingosine kinase, diacylglicerol kinase and phospholipase A2. We observed a decrease in phosphatidylinositol(4)-phosphate (8.8 ± 0.9 vs. 3.6 ± 0.7 pmol.mg-1.mim-1), and an increase in phosphatidic acid (2.2 ± 0.8 vs. 3.8 ± 1.3 pmol.mg-1.mim-1), being these lipid mediators involved in the regulation of key renal functions. Ceramide levels are augmented in kidney tissue from RBD rats (18.7 ± 1.4 vs. 21.7 ± 1.5 fmol.mg-1.min-1) indicating an ongoing renal lesion. CONCLUSION: Results point to an imbalance in the bioactive lipid generation with further consequences to key events related to kidney function, thus contributing to the establishment of chronic kidney disease.

Timing of Pulmonary Valve Replacement: How Much Can the Right Ventricle Dilate Before it Looses Its Remodeling Potential?

Congenital heart disease patients that develop secondary pulmonary regurgitation require a pulmonary valve replacement (PVR) in their follow-up. The indications for PVR in asymptomatic patients are debated. Most guidelines consider a RV end-diastolic volume (RVEDV) over 150 ml/m(2) as an indication for PVR. We analyzed clinical, echocardiographic and MRI variables of patients that underwent a surgical PVR between September 2006 and February 2013. The included patients were asymptomatic, without pulmonary stenosis and with both pre- and post-surgery MRI. Thirty-five patients (74.3 % males) were included. Mean age at PVR was 25.8 years (SD = 7.18), and weight was 64.5 Kg (SD = 12.03). The main diagnosis was tetralogy of Fallot (n = 28), pulmonary atresia (n = 2), primary pulmonary regurgitation (n = 2) and pulmonary regurgitation after percutaneous treatment (n = 2). The maximal RVEDV pre-PVR was 267 ml/m(2), and right ventricular end-systolic volume (RVESV) was 183 ml/m(2). RV size and function were established by MRI: Pre-PVR Post-PVR p RVEDV (ml/m(2)) 162 (SD = 39.1) 94 (SD = 23.6) <0.001 RVESV (ml/m(2)) 87 (SD = 28.9) 44 (SD = 15.7) <0.001 RVEF 44.8 % (SD = 8.17) 52 % (SD = 9.9) <0.001 Patients with a RVEDV under 170 ml/m(2) combined with a RVESV under 90 ml/m(2) had a favorable RV remodeling, defined as RVEDV under 110 ml/m(2) (sensitivity 87.5 %), RVESV under 55 ml/m(2) (sensitivity 100 %) and RVEF over 50 % (sensitivity 100 %). When deciding the optimal PVR timing in asymptomatic patients, both RVEDV and RVESV should be considered. Our results suggest that higher volumes than used in the clinical practice can achieve a good remodeling. Therefore, PVR could be performed later in the follow-up reducing the number of cardiac interventions.

Mitochondrial respiration and genomic analysis provide insight into the influence of the symbiotic bacterium on host trypanosomatid oxygen consumption.

Certain trypanosomatids co-evolve with an endosymbiotic bacterium in a mutualistic relationship that is characterized by intense metabolic exchanges. Symbionts were able to respire for up to 4 h after isolation from Angomonas deanei. FCCP (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone) similarly increased respiration in wild-type and aposymbiotic protozoa, though a higher maximal O2 consumption capacity was observed in the symbiont-containing cells. Rotenone, a complex I inhibitor, did not affect A. deanei respiration, whereas TTFA (thenoyltrifluoroacetone), a complex II activity inhibitor, completely blocked respiration in both strains. Antimycin A and cyanide, inhibitors of complexes III and IV, respectively, abolished O2 consumption, but the aposymbiotic protozoa were more sensitive to both compounds. Oligomycin did not affect cell respiration, whereas carboxyatractyloside (CAT), an inhibitor of the ADP-ATP translocator, slightly reduced O2 consumption. In the A. deanei genome, sequences encoding most proteins of the respiratory chain are present. The symbiont genome lost part of the electron transport system (ETS), but complex I, a cytochrome d oxidase, and FoF1-ATP synthase remain. In conclusion, this work suggests that the symbiont influences the mitochondrial respiration of the host protozoan.

A genome-wide association study on copy-number variation identifies a 11q11 loss as a candidate susceptibility variant for colorectal cancer.

Colorectal cancer (CRC) is a complex disease, and therefore its development is determined by the combination of both environmental factors and genetic variants. Although genome-wide association studies (GWAS) of SNP variation have conveniently identified 20 genetic variants so far, a significant proportion of the observed heritability is yet to be explained. Common copy-number variants (CNVs) are one of the most important genomic sources of variability, and hence a potential source to explain part of this missing genetic fraction. Therefore, we have performed a GWAS on CNVs to explore the relationship between common structural variation and CRC development. Phase 1 of the GWAS consisted of 881 cases and 667 controls from a Spanish cohort. Copy-number status was validated by quantitative PCR for each of those common CNVs potentially associated with CRC in phase I. Subsequently, SNPs were chosen as proxies for the validated CNVs for phase II replication (1,342 Spanish cases and 1,874 Spanish controls). Four common CNVs were found to be associated with CRC and were further replicated in Phase II. Finally, we found that SNP rs1944682, tagging a 11q11 CNV, was nominally associated with CRC susceptibility (p value = 0.039; OR = 1.122). This locus has been previously related to extreme obesity phenotypes, which could suggest a relationship between body weight and CRC susceptibility.

Functional diversity of phytochrome family in the control of light and gibberellin-mediated germination in Arabidopsis.

In several species, seed germination is regulated by light in a way that restricts seedling emergence to the environmental conditions that are likely to be favourable for the success of the new individual, and therefore, this behaviour is recognized to have adaptive value. The phytochromes are one of the most relevant photoreceptors involved in light perception by plants. We explored the redundancy and diversity functions of the phytochrome family in the control of seed responsiveness to light and gibberellins (GA) by using a set of phytochrome mutants of Arabidopsis. Our data show that, in addition to the well-known role of phyB in the promotion of germination in response to high red to far-red ratios (R/FR), phyE and phyD stimulate germination at very low R/FR ratios, probably by promoting the action of phyA. Further, we show that phyC regulates negatively the seed responsiveness to light, unravelling unexpected functions for phyC in seed germination. Finally, we find that seed responsiveness to GA is mainly controlled by phyB, with phyC, phyD and phyE having relevant roles when acting in a phyB-deficient background. Our results indicate that phytochromes have multiple and complex roles during germination depending on the active photoreceptor background.

Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration.

The development of genotyping technologies has allowed for wider screening for inherited causes of variable outcomes following drug administration. We have performed a genome-wide association study (GWAS) on 221 colorectal cancer (CRC) patients that had been treated with 5-fluorouracil (5-FU), either alone or in combination with oxaliplatin (FOLFOX). A validation set of 791 patients was also studied. Seven SNPs (rs16857540, rs2465403, rs10876844, rs10784749, rs17626122, rs7325568 and rs4243761) showed evidence of association (pooled P-values 0.020, 9.426E-03, 0.010, 0.017, 0.042, 2.302E-04, 2.803E-03) with adverse drug reactions (ADRs). This is the first study to explore the genetic basis of inter-individual variation in toxicity responses to the administration of 5-FU or FOLFOX in CRC patients on a genome-wide scale.

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.

Enforced expression of MLL-AF4 fusion in cord blood CD34+ cells enhances the hematopoietic repopulating cell function and clonogenic potential but is not sufficient to initiate leukemia.

Infant acute lymphoblastic leukemia harboring the fusion mixed-lineage leukemia (MLL)-AF4 is associated with a dismal prognosis and very brief latency. Our limited understanding of transformation by MLL-AF4 is reflected in murine models, which do not accurately recapitulate the human disease. Human models for MLL-AF4 disease do not exist. Hematopoietic stem or progenitor cells (HSPCs) represent probable targets for transformation. Here, we explored in vitro and in vivo the impact of the enforced expression of MLL-AF4 in human cord blood-derived CD34(+) HSPCs. Intrabone marrow transplantation into NOD/SCID-IL2Rγ(-/-) mice revealed an enhanced multilineage hematopoietic engraftment, efficiency, and homing to other hematopoietic sites on enforced expression of MLL-AF4. Lentiviral transduction of MLL-AF4 into CD34(+) HSPCs increased the in vitro clonogenic potential of CD34(+) progenitors and promoted their proliferation. Consequently, cell cycle and apoptosis analyses suggest that MLL-AF4 conveys a selective proliferation coupled to a survival advantage, which correlates with changes in the expression of genes involved in apoptosis, sensing DNA damage and DNA repair. However, MLL-AF4 expression was insufficient to initiate leukemogenesis on its own, indicating that either additional hits (or reciprocal AF4-MLL product) may be required to initiate ALL or that cord blood-derived CD34(+) HSPCs are not the appropriate cellular target for MLL-AF4-mediated ALL.

Infective endocarditis in congenital heart disease: a frequent community-acquired complication.

BACKGROUND: Infective endocarditis (IE) is a severe complication in patients with congenital heart disease (CHD). Epidemiology, etiology, and outcome in this group are different to those of patients with acquired heart disease. METHODS: We reviewed all cases of proven and probable IE (Duke's criteria) diagnosed in our center during the last two decades. RESULTS: We observed 45 cases of IE in patients with CHD (age range 8 months to 35 years); these represented 5.5 % of all the episodes of IE in our institution during the study period. The most frequent CHD were ventricular septal defect (31 %), tetralogy of Fallot (19 %), and atrioventricular septal defect (11 %). Twenty cases of IE (44 %) were recorded in patients with non-corrected native-valve CHD. Of the 24 patients with prosthetic-valve IE, post-operative acquisition during the first 6 months was confirmed in 11 patients (range 4-110 days). IE was community-acquired in 62 % of cases. Streptococcus spp. were the most frequent etiologic agents (33 %), followed by Staphylococcus spp. (32 %). Surgery was required to treat IE in 47 % of patients (52 % in prosthetic-valve IE and 41 % in native-valve IE, p = ns). In comparison to native-valve IE, prosthetic-valve IE was significantly more nosocomial-acquired (61 vs. 14 %, p = 0.002), presented a higher heart failure rate at diagnosis (39 vs. 9 %, p = 0.035), and developed more breakthrough bacteremia episodes (19 vs. 0 %, p = 0.048). Global mortality was 24 % (75 % in patients with prosthetic-valve IE who required surgery and 0 % in patients with native-valve IE who required surgery, p = 0.001). Multivariate analysis excluding breakthrough bacteremia (100 % mortality in this condition) confirmed that nosocomial IE [odds ratio (OR), 23.7; 95 % confidence interval (CI), 2.3-239.9] and the presence of heart failure at diagnosis of IE (OR, 25.9; 95 % CI, 2.5-269.6) were independent factors associated with mortality. CONCLUSION: Half of all cases of IE in patients with CHD occurred in patients with non-corrected native-valve CHD and two-thirds were community-acquired. Streptococcus spp. were the most frequent etiological agents. Patients with prosthetic-valve IE present a worse outcome, especially those requiring surgery. Breakthrough bacteremia, nosocomial IE, and heart failure are independent factors of mortality in patients with CHD presenting IE.

Treatment of chronic sternal fistulae following cardiac surgery with a bone substitute.

Chronic sternal infection is a relatively rare complication following cardiac surgery that can cause high morbidity and mortality and can require repeated surgical procedures, including sternal resection, to resolve. However, preserving sternal integrity is essential, particularly in children. A variety of conservative treatments for this complication of cardiac surgery have been reported. Here, we report three cases of children in whom a bone substitute containing tricalcium phosphate and hydroxyapatite was used to fill sternal defects. After extensive surgical debridement, this method yielded primary wound closure with good resolution, preventing the recurrence of sternal infection.

Nongenomic signaling pathways triggered by thyroid hormones and their metabolite 3-iodothyronamine on the cardiovascular system.

Thyroid hormones play a wide range of important physiological activities in almost all organism. As changes in these hormones levels-observed in hypothyroidism and hyperthyroidism-promote serious derangements of the cardiovascular system, it is important to know their mechanisms of action. Although the classic genomic actions which are dependent on interaction with nuclear receptors to modulate cardiac myocytes genes expression, there is growing evidence about T(3) and T(4)-triggered nongenomic pathways, resulted from their binding to plasma membrane, cytoplasm, or mitocondrial receptors that leads to a rapidly regulation of cardiac functions. Interestingly both actions converge to amplify thyroid hormone effects on cardiovascular system. T(3) and T(4) nongenomic actions modify inotropic and chronotropic effects, cardiac action potential duration, cardiac growth, and myocyte shape by protein translation through protein kinases-dependent signaling cascades, which include PKA, PKC, PI3K, and MAPK, and changes on ion channels and pumps activity. In respect to the decreased systemic vascular resistance seen in hyperthyroidism, T(3) appears to activate NOS or ATP-sensitive K(+) channels. In addition, a novel biologically active T(4)-derived metabolite has been described, 3-iodothyronamine, T(1)AM, which also acts through membrane receptors to mediate nongenomic cardiac effects. This metabolite influences the physiological manifestations of thyroid hormone actions by inducing opposite effects from those stimulated by T(3) and T(4), such as negative inotropic and chronotropic effects. Therefore, beyond genomic and nongenomic effects of thyroid hormones, it is crucial for there to be an equilibrium between T(3) or T(4) and T(1)AM levels for maintaining cardiac homeostasis.

[Development of the Q-PEX standard for quality certification of pharmaceutical care for outpatients of Pharmacy services]. / Desarrollo de la norma Q-PEX de certificación de calidad de la atención farmacéutica a pacientes externos de los servicios de Farmacia.

OBJECTIVE: The objective of this study is to describe the process of creation and development of the quality certification standard for pharmaceutical care for outpatients of the Pharmacy services. METHOD: The methodology was carried out by a group of experts from the Spanish Society of Hospital Pharmacy (SEFH) and consisted of three phases: situation analysis, development of the standard and definition of the self-assessment tool and, finally, piloting in several hospitals, determining its feasibility, carrying out a new revision and readaptation. RESULTS: A standard was defined with 118 items distributed in ten areas. Of these, 19 were considered compulsory, 36 basic, 40 medium and 23 advanced. Three levels of certification were established, as well as the definition and percentages of compliance with the requirements. The certification process was divided into two stages, the one of previous preparation and the audit itself, where the initial certification would be covered, with four phases - first three led by the certification Company, and the last one by SEFH and the subsequent follow-up and re-certification audits. Two hospitals piloted the process carried out the piloting of the whole process, both obtaining a basic level after the adoption of measures and corrective actions, after which the final definition of the external evaluation of the standard and the name of the standard was agreed upon «Q-PEX¼, as well as, the registration of the intellectual property of said standard in July-2020. CONCLUSIONS: The standard for certification of the quality of pharmaceutical care for outpatients developed aims to help the continuous advancement of Hospital Pharmacy services.

Recent epidemiological trends in extrapulmonary TB in Galicia, Spain.

OBJECTIVE: To describe the epidemiological trends and characteristics of extrapulmonary tuberculosis (EPTB) in Galicia, Spain, from 2000 to 2019.METHODS: This was a retrospective cohort study based on data from the Galician TB information system.RESULTS: Of the total number of TB cases (n = 15,871), 5,428 (34.2%) had EPTB. The absolute number of cases and incidence of EPTB decreased dramatically (from 480 cases and 17.8 cases/100,000 in 2000, to 172 and 6.4 cases/100,000 in 2019, respectively), with a mean annual decrease of respectively 64% and 4.7% for absolute cases and incidence rates. The risk for EPTB was higher in men than in women (RR 3.86, 95% CI 3.66-4.07). The most frequent age group was 15-44 years (2,234 patients, 41.2%); overall reductions per age group were 82% (0-14 years), 75% (15-44 years), 44% (45-64 years) and 63% (≥65 years), with statistically significant differences. The most frequently locations were the pleura (1,916 cases; 35.3%) and the lymph nodes (1,504; 27.7%).CONCLUSION: The incidence of EPTB in Galicia has decreased significantly in the last 20 years. The epidemiological characteristics have not changed, except for the number of patients with risk factors. This improvement of EPTB epidemiological trends coincides with the implementation of the programme for the prevention and control of TB, which suggests that it has been very effective in the control of the EPTB.

Paclitaxel and cisplatin in the treatment of metastatic non-small-cell lung cancer during pregnancy.

The concomitant occurrence of cancer during pregnancy is a rare event. The cancers most frequently detected during pregnancy are breast, cervical, melanoma, ovarian, leukaemia and lymphoma, however the diagnosis of lung cancer during pregnancy is particularly exceptional. In this case, we report on a pregnant woman who was diagnosed with non-small-cell lung cancer and received therapy with paclitaxel and cisplatin.

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.

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.