Nanostructured Lipid Carriers as a Strategy to Improve the In Vitro Schistosomiasis Activity of Praziquantel.

Praziquantel (PZQ) is a pyrazinoisoquinoline anthelmintic that was discovered in 1972 by Bayer Germany. Currently, due to its efficacy, PZQ is the drug of choice against all species of Schistosoma. Although widely used, PZQ exhibits low and erratic bioavailability because of its poor water solubility. Nanostructured lipid carriers (NLC), second-generation solid lipid nanoparticles, were developed in the 1990s to improve the bioavailability of poorly water soluble drugs. The aim of this study was to investigate nanostructured lipid carriers as a strategy to improve the efficacy of PZQ in S. mansoni treatment. We prepared NLC2 and NLC4 by adding seventy percent glycerol monostearate (GMS) as the solid lipid, 30% oleic acid (OA) as the liquid lipid and two surfactant systems containing either soybean phosphatidylcholine/poloxamer (PC/P-407) or phosphatidylcholine/Tween 60 (PC/T60), respectively. The carriers were characterized by nuclear magnetic resonance, differential scanning calorimetry, thermogravimetric analysis and Fourier transform-infrared spectroscopy. The safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. The results showed that the encapsulation of PZQ in NLC2 or NLC4 improved the safety profile of the drug. Treatment efficacy was evaluated on the S. mansoni BH strain. PZQ-NLC2 and PZQ-NLC4 demonstrated an improved efficacy in comparison with free PZQ. The results showed that the intestinal transport of free PZQ and PZQ-NLC2 was similar. However, we observed that the concentration of PZQ absorbed was smaller when PZQ was loaded in NLC4. The difference between the amounts of absorbed PZQ could indicate that the presence of T60 in the nanoparticles (NLC4) increased the rigid lipid matrix, prolonging release of the drug. Both systems showed considerable in vitro activity against S. mansoni, suggesting that these systems may be a promising platform for the administration of PZQ for treating schistosomiasis.

The Caries Assessment Spectrum and Treatment (CAST) instrument: construct validation.

The Caries Assessment Spectrum and Treatment (CAST) is a newly developed epidemiological instrument. The aim of this study was to investigate its construct validity. Four calibrated examiners, using CAST codes 0-6, visually examined 109 surfaces of extracted and exfoliated teeth. These teeth were then hemisectioned, photographed, and assessed histologically by two calibrated examiners using the Downer criteria. Twenty-eight of the 109 teeth were scanned using micro-computed tomography (micro-CT) and assessed by the same examiners using the same criteria. Validation was determined through calculation of the sensitivity, specificity, and Youden index for two categories of carious lesions examined visually, with histology and micro-CT as gold standards. Interexaminer consistency was κ = 0.76: SE ± 0.05 between visual and histological assessments of teeth and was κ = 0.89: SE ± 0.08 between visual and micro-CT assessments. For the category 'healthy' vs. 'diseased' (CAST codes 0-2 vs. CAST codes 3-6), sensitivity, specificity, and Youden index values of 100%, 92.9%, and 93%, respectively, for micro-CT, and 96.6%, 86%, and 83%, respectively, for histology, were obtained. For the category 'dentine' vs. 'non-dentine lesions' (CAST codes 0-3 vs. CAST codes 4-6) sensitivity, specificity, and Youden index values of 90%, 100%, and 90%, respectively, for micro-CT, and 81.4%, 100%, and 81%, respectively, for histology, were obtained. Construct validity of the CAST instrument was obtained.

The Caries Assessment Spectrum and Treatment (CAST) index: face and content validation.

OBJECTIVES: The aim of this study was to establish the face and content validity of the Caries Assessment Spectrum and Treatment (CAST) index. This hierarchical epidemiological index consists of 10 codes covering the spectrum of carious lesion progression and describing conditions ranging from the absence of carious lesions to the presence of sealants and restorations, the presence of lesions in enamel and dentine, and the presence of advanced stages of carious lesion in pulpal tissue and tissue surrounding the tooth. METHODS: Using the RAND modified e-Delphi consensus method, a set of 17 statements related to the content, including the codes and descriptions used, and suitability of the CAST index were scored on a scale of 1-9 by 15 senior epidemiologists from 15 countries over three rounds of assessment. Agreement of ≥ 75% was required to indicate consensus on a statement. RESULTS: Consensus was reached on 14 statements in the first round, none in the second and on the remaining three statements in the third round. To obtain feedback on the initial validation of the index and to test its external validity, 41 epidemiologists from 24 countries were requested to assess the validated statements. Minor changes to 10 of the 17 statements' content and descriptions were suggested; this necessitated the resubmission of the modified CAST index to the original 15 epidemiologists. Consensus of ≥ 80% was reached on all 10 statements regarding codes and their descriptions. CONCLUSIONS: After a total of four rounds with the panel members and one round with the feedback group, the CAST index was approved for face and content validity. External validity was obtained. The participating epidemiologists found the RAND modified e-Delphi consensus method to be a suitable instrument for reaching consensus.

Lipid Nanocarriers for Hyperproliferative Skin Diseases.

Hyperproliferative skin diseases (HSD) are a group of diseases that include cancers, pre-cancerous lesions and diseases of unknown etiology that present different skin manifestations in terms of the degree and distribution of the injuries. Anti-proliferative agents used to treat these diseases are so diverse, including 5-aminolevulinic acid, 5-fluorouracil, imiquimod, methotrexate, paclitaxel, podophyllotoxin, realgar, and corticosteroids in general. These drugs usually have low aqueous solubility, which consequently decreases skin permeation. Thus, their incorporation in lipid nanocarriers has been proposed with the main objective to increase the effectiveness of topical treatment and reduce side effects. This manuscript aims to describe the advantages of using lipid nanoparticles and liposomes that can be used to load diversity of chemically different drugs for the treatment of HSD.

Influence of chromium propionate dose and feeding regimen on growth performance and carcass composition of pigs housed in a commercial environment.

Although chromium (Cr) feeding study results have been variable, our hypothesis was feeding a regimen that changed dosage over time would result in a larger positive response in growth performance and carcass characteristics. In Exp. 1, a total of 1,206 pigs (PIC 337 × 1050, initial BW 28.7 kg) were used with 27 pigs per pen and 9 pens per treatment. Diets were corn-soybean meal-dried distillers grains with solubles based and were fed in a five-phase feeding program. Treatments were arranged as a 2 × 2 + 1 factorial with a control diet containing no added Cr propionate (Kemin Industries Inc., Des Moines, IA), or diets with either 100 or 200 µg/kg added Cr during the grower (dietary phases 1 and 2) and/or finisher (dietary phases 3, 4, and 5) periods. During the grower period, ADG and G:F were similar among pigs fed the control or 100 µg/kg added Cr diets, but decreased in pigs fed 200 µg/kg Cr (quadratic, P ≤ 0.001). During the finisher period, pigs supplemented with 200 µg/kg added Cr had the greatest ADG and G:F (quadratic, P ≤ 0.019). Overall, increasing Cr had no effect on ADG or ADFI; but G:F was greatest (quadratic, P = 0.020) when pigs were fed 100 µg/kg of added Cr throughout. Carcass characteristics were not influenced by Cr dosage or feeding regimen. In Exp. 2, a total of 1,206 pigs (PIC 359 × 1050, initial BW 48.9 kg) were used with 27 pigs per pen and 15 pens per treatment. Diets were corn-soybean meal, dried distillers grains with solubles based and were fed in four phases. There were three dietary treatments: a diet with no added Cr for both grower (dietary phase 1 and 2) and finisher (dietary phase 3 and 4) periods, a diet with 200 µg/kg added Cr during the grower and 100 µg/kg added Cr during the finisher periods, or a diet with 200 µg/kg added Cr for both periods. Addition of 200 µg/kg Cr in both periods marginally increased (P < 0.10) ADG compared with pigs fed no added Cr. There was no evidence (P ≥ 0.523) of added Cr influencing overall ADFI and G:F. Percentage carcass yield was reduced (P = 0.018) when Cr was added at 200 µg/kg for both periods, with no evidence of differences (P ≥ 0.206) in other carcass characteristics. In summary, overall G:F was improved in Exp. 1, and ADG in Exp. 2, by added Cr, but there was no evidence that different feeding regimens will consistently result in improved performance. However, these data are consistent with the literature in that added Cr in growing-finishing pigs diets improves, albeit small, ADG or G:F.

Determining the influence of chromium propionate and Yucca schidigera on growth performance and carcass composition of pigs housed in a commercial environment.

Two experiments were conducted to determine the effects of feeding chromium propionate (Cr; Kemin Industries, Inc., Des Moines, IA) and a Yucca schidigera-based extract (YS; Distributors Processing, Inc., Porterville, CA) on growth performance of finishing pigs housed in commercial conditions. In experiment 1, a total of 1,188 pigs (PIC 337 × 1050; initially 27.3 ± 0.48 kg body weight [BW]) with 27 pigs per pen and 11 pens per treatment were split by sex upon arrival at the facility and were randomly allotted to groups of four pens blocked by BW. Diets were corn-soybean meal-dried distillers grains with solubles-based and were fed in five phases. Treatments were arranged as a 2 × 2 factorial with main effects of Cr (0 vs. 200 µg/kg) or YS (0 vs. 62.5 mg/kg YS-based feed grade concentrate). Overall, adding Cr alone increased (P = 0.049) average daily feed intake (ADFI), and inclusion of YS resulted in a marginally significant increase (P = 0.077) in ADFI. Backfat depth was increased (P = 0.043) and lean percentage was decreased (P = 0.011) with added Cr. In experiment 2, a total of 2,430 pigs (PIC 359 × 1050; initially 29.3 ± 0.43 kg BW) were placed in balanced mixed-sex pens with 27 pigs per pen, blocked by average pen BW, and randomly assigned to one of six dietary treatments with 14 pens per treatment. Diets were corn-soybean meal-based and were formulated in five dietary phases. Treatments were arranged in a 2 × 3 factorial with main effects of Cr (0 vs. 200 µg/kg added Cr), and YS extract (0, 62.5, or 125 mg/kg YS-based feed grade concentrate). Overall, a marginally significant (linear, P = 0.072) Cr × YS interaction was observed for average daily gain (ADG) where there was insufficient evidence of a difference with increasing YS in diets not including added Cr (P ≥ 0.109); however, ADG increased (quadratic, P = 0.026) with YS addition in treatments fed 200 µg/kg added Cr. For overall ADFI, a marginally significant (linear, P = 0.071) Cr × YS interaction was observed where YS increased ADFI with 200 µg/kg added Cr (linear, P = 0.031), however, did not when diets contained no added Cr (P = 0.700). A marginally significant reduction in gain:feed ratio was observed when 62.5 mg/kg YS was included (quadratic, P = 0.053), and final BW and hot carcass weight were lowest with 62.5 mg/kg YS (quadratic, P = 0.012). In summary, adding Cr propionate along with YS led to modest changes in performance with the greatest benefit observed with 200 µg/kg Cr and 125 mg/kg YS-based feed grade concentrate.

Development and In Vitro Evaluation of Lyotropic Liquid Crystals for the Controlled Release of Dexamethasone.

In this study, amphiphilic polymers were investigated as biomaterials that can control dexamethasone (DXM) release. Such materials present interfacial properties in the presence of water and an oily phase that can result in lyotropic liquid crystalline systems (LLCS). In addition, they can form colloidal nanostructures similar to those in living organisms, such as bilayers and hexagonal and cubic phases, which can be exploited to solubilize lipophilic drugs to sustain their release and enhance bioavailability. It was possible to obtain lamellar and hexagonal phases when combining polyoxyethylene (20) cetyl ether (CETETH-20) polymer with oleic acid (OA), N-methylpyrrolidone (P), isopropyl myristate (IM), and water. The phases were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological, textural, and bioadhesion analyses followed by an in vitro release assay. All samples showed elastic behavior in the rheology studies and hexagonal samples containing P and IM showed the highest adhesiveness. The drug release profile of all LLCS presented an average lag time of 3 h and was best fitted to the Korsmeyer-Peppas and Weibull models, with controlled release governed by a combination of diffusion and erosion mechanisms. These systems are potential carriers for DXM and can be explored in several routes of administration, providing potential advantages over conventional pharmaceutical forms.