Inhalable Mannosylated Rifampicin-Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy.

Among respiratory infections, tuberculosis was the second deadliest infectious disease in 2020 behind COVID-19. Inhalable nanocarriers offer the possibility of actively targeting anti-tuberculosis drugs to the lungs, especially to alveolar macrophages (cellular reservoirs of the Mycobacterium tuberculosis). Our strategy was based on the development of a mannose-decorated micellar nanoformulation based in Soluplus® to co-encapsulate rifampicin and curcumin. The former is one of the most effective anti-tuberculosis first-line drugs, while curcumin has demonstrated potential anti-mycobacterial properties. Mannose-coated rifampicin (10 mg/mL)-curcumin (5 mg/mL)-loaded polymeric micelles (10% w/v) demonstrated excellent colloidal properties with micellar size ~108 ± 1 nm after freeze-drying, and they remain stable under dilution in simulated interstitial lung fluid. Drug-loaded polymeric micelles were suitable for drug delivery to the deep lung with lung accumulation, according to the in vitro nebulization studies and the in vivo biodistribution assays of radiolabeled (99mTc) polymeric micelles, respectively. Hence, the nanoformulation did not exhibit hemolytic potential. Interestingly, the addition of mannose significantly improved (5.2-fold) the microbicidal efficacy against Mycobacterium tuberculosis H37Rv of the drug-co-loaded systems in comparison with their counterpart mannose-free polymeric micelles. Thus, this novel inhaled nanoformulation has demonstrated its potential for active drug delivery in pulmonary tuberculosis therapy.

Entrapment of Citrus limon var. pompia Essential Oil or Pure Citral in Liposomes Tailored as Mouthwash for the Treatment of Oral Cavity Diseases.

This work aimed at developing a mouthwash based on liposomes loading Citrus limon var. pompia essential oil or citral to treat oropharyngeal diseases. Vesicles were prepared by dispersing phosphatidylcholine and pompia essential oil or citral at increasing amounts (12, 25 and 50 mg/mL) in water. Transparent vesicle dispersions were obtained by direct sonication avoiding the use of organic solvents. Cryogenic transmission electron microscopy (cryo-TEM) confirmed the formation of unilamellar, spherical and regularly shaped vesicles. Essential oil and citral loaded liposomes were small in size (~110 and ~100 nm, respectively) and negatively charged. Liposomes, especially those loading citral, were highly stable as their physico-chemical properties did not change during storage. The formulations were highly biocompatible against keratinocytes, were able to counteract the damages induced in cells by using hydrogen peroxide, and able to increase the rate of skin repair. In addition, liposomes loading citral at higher concentrations inhibited the proliferation of cariogenic bacterium.

Growth charts of head length and breadth for regional areas? A study in Sardinia (Italy).

There exist few standards of head length and breadth from childhood to adulthood in Europoid populations. Moreover, such standards are based on samples that cannot be used as references for all populations since they were taken from different ethnic groups and from different periods. The aims of this study were: (1) to test whether standards derived from North Americans of European extraction can be used to assess the Sardinian population; and (2) to produce growth charts for head length and breadth for Sardinian males and females from 3 to 22 years of age. The cross sectional sample consisted of 9,721 subjects of Sardinian origin (4,884 males and 4,837 females), aged 3-22 years, measured from 1998 to 2008. Growth percentiles were produced with the LMS method. The mean values for each sex in each age class (3-18 years) are almost always significantly lower for both head length and breadth than the corresponding North American values. The exceptions are the head length of boys of 14 years and girls of 16-18 years where values for Sardinians are lower, but not significantly so. The results show that the North American standards are not appropriate for the assessment of Sardinian children. For the Sardinian population, specific regional growth charts should be used to correctly evaluate the normal range and the cut-off points of the extreme percentiles.

The need of specific standards for head dimensions of urban Sardinian boys.

In the 1997-1998 and 1998-1999 school years we measured head dimensions of 1600 boys from 6 to 13 years attending elementary and middle schools in towns of the Cagliari area (Sardinia, Italy). For each age, we compared the mean values for circumference, length and width of the head with Canadian standards, widely used by Sardinian pediatricians. The t-test shows that the means of the three variables are significantly lower in the Cagliari boys than in their Canadian contemporaries, with the exception of head circumference in 6 and 7 year-olds, and of head width in 10 year-olds. Therefore, it is necessary to produce specific growth charts for circumference, length and width of the head of Sardinian children rather than evaluate their growth using standards of populations with different ethnic, geographical and socio-economic backgrounds.

Blood and hair lead levels in boys and girls living in two Sardinian towns at different risks of lead pollution.

This study reports blood and hair lead levels measured in 1998 in 222 children from two Sardinian towns: Portoscuso and Sestu. Portoscuso is in a polluted area of Sardinia due to its vicinity to the industrial zone of Portovesme. As a consequence of its economy and location, Sestu is not exposed to lead pollution. Blood lead (PbB) concentration was determined in heparinized venous blood samples by graphite furnace atomic absorption spectrophotometry (AAS). Hair lead (PbH) concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). With respect to blood lead levels, the boys of Portoscuso have the highest arithmetic mean value (11.30 microg/dL), followed by the Portoscuso girls (7.39 microg/dL); they are followed, but with much lower values, by the boys (4.09 microg/dL) and girls (3.34 microg/dL) of Setsu. For hair lead levels, the Portoscuso boys have the highest arithmetic mean value (15.51 microg/g), followed by the Portoscuso girls (8.82 microg/g) and the Sestu boys (4.03 microg/g) and girls (2.83 microg/g). Therefore the mean values of PbB and PbH follow similar patterns in the boys and girls of the two Sardinian towns. Two-way ANOVA reveals a significant effect of sex and town on log PbB and log PbH. Moreover, values of the Bravais-Pearson coefficients of correlation between log PbB and log PbH are statistically significant for the total sample (r=0.5086; P<0.001), for males (r=0.4275; P<0.01), and for females (r=0.4859, P<0.001). The sensitivity of the hair lead analysis in identifying lead concentrations above 10 microg/g is 49%. The results support the hypothesis that hair lead levels can be considered an indicator of different relative exposure of populations to lead pollution.