Fabrication and Assessment of Orodispersible Tablets Loaded with Cubosomes for the Improved Anticancer Activity of Simvastatin against the MDA-MB-231 Breast Cancer Cell Line.

Various factors limit the use of simvastatin as an anticancer drug. Therefore, this study aimed to analyse simvastatin (SIM)-loaded cubosome efficacy against breast cancer. SIM-loaded cubosomes were prepared using the emulsification method using different glyceryl monooleate, Pluronic F127 (PF-127), and polyvinyl alcohol (PVA) ratios. The best cubosomal formula was subjected to an in vitro cytotoxicity analysis using the human breast cancer cell line, MDA-MB-231 (MDA) (ATCC, HTB-26), and formulated as oral disintegrating tablets through direct compression. PF-127 and PVA positively affected drug loading, and the entrapment efficiency percentage of different SIM-cubosomal formulations ranged from 33.52% to 80.80%. Vesicle size ranged from 181.9 ± 0.50 to 316.6 ± 1.25 nm. PF-127 enhanced in vitro SIM release from cubosome formulations due to its solubilising action on SIM. The in vitro dissolution analysis indicated that SIM exhibited an initial dissolution of 10.4 ± 0.25% within the first 5 min, and 63.5 ± 0.29% of the loaded drug was released after 1 h. Moreover, cubosome formula F3 at 25 and 50 µg/mL doses significantly decreased MDA cell viability compared to the 12.5 µg/mL dose. The untreated SIM suspension and drug-free cubosomes at all doses had no significant influence on MDA cell viability compared to the control.

Correlation of In Vivo and In Vitro Assay Results for Assessment of Free Radical Scavenging Activity of Green Tea Nutraceuticals.

Green tea (GT)-derived catechins; epigallocatechin gallate (EGCG) in particular are commonly used nutraceuticals for their free-radical scavenging activity (FRSA). The influence of photodegradation on the protective power of GT nutracenticals against oxidative stress was thoroughly explored. Photodegradation of GT extracts was carried out and monitored using orthogonal stability-indicating testing protocol; in vitro and in vivo assays. Total polyphenol content (TPC) and FRSA were determined spectrophotometrically while EGCG was selectively monitored using SPE-HPLC. In vivo assessment of photodegraded samples was investigated via measuring a number of biomarkers for hepatic oxidative stress and apoptosis (caspase-3, inducible nitric oxide synthase, nitric oxide, mitogen-activated protein kinase, glutathione, thiobarbituric acid reactive substances, nuclear factor kappa beta, and nuclear factor erythroid 2-related factor) as well as liver damage (alanine transaminase and aspartate transaminase) in serum of rats previously subjected to oxidative stress. Results showed complete degradation of EGCG in photodegraded green tea samples with no correlation with either TPC or FRSA. On the other hand, in vivo assay results revealed not only loss of activity but formation of harmful pro-oxidants. Photostability was found crucial for the protective effect of GT extract against lead acetate insult. Results confirmed that careful design of quality control protocols requires correlation of chemical assays to bioassays to verify efficacy, stability, and most importantly safety of nutraceuticals.

Assessment of changes in quality of life among patients in the SAVE Study - Sirolimus as therapeutic Approach to uVEitis: a randomized study to assess the safety and bioactivity of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis.

BACKGROUND: The National Eye Institute 39-Question Visual Function Questionnaire (NEI VFQ-39) is an indicator of vision-related quality of life (QoL). The NEI VFQ-39 is used to assess the QoL in patients with non-infectious posterior uveitis, intermediate uveitis, or panuveitis, treated with subconjunctival (SCJ) or intravitreal (IVT) sirolimus as an immunomodulatory therapeutic (IMT) agent, delivered subconjunctivally (SCJ) or intravitreally (IVT) (the SAVE Study). Thirty subjects with non-infectious uveitis were randomized (SCJ:IVT, 1:1) for a prospective clinical trial. The 39-Question Visual Function Questionnaire (VFQ-39) was administered at baseline (BL), month 6 (M6), and month 12 (M12) visits. The survey measures self-reported vision health status for patients with chronic eye disease and assesses the effects of visual impairment on both task-oriented visual function and general health domains. In accordance to the NEI-VFQ Manual, each patient's questionnaire was converted to a scaled score between 0 (worst) and 100 (best), and median scores were calculated for each of the subcategories and overall composite score at BL, M6, and M12. Wilcoxon signed-rank test was performed. RESULTS: Twenty-six patients completed the VFQ-39 at BL and M6, whereas 23 patients completed it at M12. Patients showed a significant improvement in pooled composite scores from BL to M6 and BL to M12. Analysis by treatment groups showed that intravitreal injection of sirolimus is better tolerated. CONCLUSIONS: Sirolimus has demonstrated bioactivity as an IMT and corticosteroid-sparing agent to treat non-infectious uveitis. Patients receiving intravitreal injection of sirolimus showed overall improvement of vision-related health while those receiving subconjunctival injections did not. Larger randomized control trials with sirolimus are indicated to validate these results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00908466.

Assessment of oxygen saturation in retinal vessels of normal subjects and diabetic patients with and without retinopathy using Flow Oximetry System.

PURPOSE: To assess oxygen saturation (StO2) in retinal vessels of normal subjects and diabetic patients with and without retinopathy using the modified version of the Flow Oximetry System (FOS) and a novel assessment software. METHODS: The FOS and novel assessment software were used to determine StO2 levels in arteries and veins located between 1 and 2 mm from the margin of the optic disc and in the macular area. RESULTS: Eighteen normal subjects, 15 diabetics without diabetic retinopathy (DM no DR), and 11 with non-proliferative diabetic retinopathy (NPDR) were included in final analysis. The mean [± standard deviation (SD)] StO2 in retinal arteries was 96.9%±3.8% in normal subjects; 97.4%±3.7% in DM no DR; and 98.4%±2.0% in NPDR. The mean venous StO2 was 57.5%±6.8% in normal subjects; 57.4%±7.5% in DM no DR; and 51.8%±6.8% in NPDR. The mean arterial and venous StO2 across the three groups were not statistically different (P=0.498 and P=0.071, respectively). The arterio-venous differences between the three study groups, however, were found to be statistically significant (P=0.015). Pairwise comparisons have demonstrated significant differences when comparing the A-V difference in the NPDR group to either normal subjects (P=0.02) or diabetic patients without DR (P=0.04). CONCLUSIONS: The arterio-venous difference was greater, and statistically significant, in patients with NPDR when compared to normal subjects and to patients with diabetes and no retinopathy. The mean venous StO2 was lower, but not statistically significant, in NPDR compared with diabetics without retinopathy and with normal subjects.

Assessment of Central Retinal Sensitivity Employing Two Types of Microperimetry Devices.

PURPOSE: To compare the retinal sensitivity measurements obtained with two microperimeters, the Micro-Perimeter 1 (MP-1) and the Optos optical coherence tomography (OCT)/scanning laser ophthalmoscope (SLO) in subjects with and without maculopathies. METHODS: Forty-five eyes with no known ocular disease and 47 eyes with maculopathies were examined using both microperimeters. A contrast-adjusted scale was applied to resolve the different stimuli and background luminance existing between the two devices. RESULTS: There was a strong ceiling effect with the MP-1 in the healthy group, with 90.1% (1136 of 1260) test points clustered at 20 dB. The mean sensitivity for the corresponding points in the OCT/SLO was 25.8 ± 1.9 dB. A floor effect was also observed with the OCT/SLO in the maculopathy group with 9.7% (128 of 1316) points clustered at 9-dB values. The corresponding mean sensitivity in the MP-1 was 1.7 ± 3.9 dB. A regression equation between the two microperimeters was established in the common 10 to19 dB intervals as: OCT/SLO = 15.6 + 0.564 × MP-1 - 0.009 × MP-12 + k (k is an individual point constant; MP-1 coefficient P < 0.001; MP-12 coefficient P = 0.006). CONCLUSION: The OCT/SLO and the MP-1 provide two different ranges of contrasts for microperimetry examination. Broadening the dynamic range may minimize the constraint of the ceiling and floor effect. There is a significant mathematical relationship in the common interval of the contrast scale. TRANSLATIONAL RELEVANCE: Applying a unified and broadened dynamic range in different types of microperimeters will help to generate consistent clinical reference for measurements.

Evaluating the impact of LED bulb development on the economic viability of ultraviolet technology for disinfection.

Ultraviolet (UV) technologies have been very successful in disinfection applications due to their ability to inactivate microorganisms without producing harmful disinfection by-products. However, there have been a number of concerns associated with the use of conventional UV systems such as hazardous mercury content, high capital investment and reduced electrical efficiency. These concerns have set limitations for the use of UV processes. The study evaluates the development of light emitting diode (LED) technology as an alternative UV source over the last 5 years, analyses the projections provided by the researchers and UV LED manufacturers and presents the information in a cost model with the aim to predict the timeline at which UV LED will compete with traditional UV low pressure high output technology in the commercial market at full-scale residential and industrial disinfection applications.

Assessment of the pharmaceutical quality of marketed enteric coated pantoprazole sodium sesquihydrate products.

Pantoprazole sodium sesquihydrate (PSS) is a proton pump inhibitor, used in acid-related disorders, like peptic ulcer and gastroesophageal reflux. Increasing the number of pantoprazole containing products in the market, raises questions of its efficacy and generic substitution. The pharmaceutical quality of 6 generic PSS enteric coated tablets in 2 local markets was assessed relative to the innovator product (pantozol®). Uniformity of dosage unit, disintegration and in vitro drug release were determined using United States pharmacopeia for delayed release tablets. The similarity factor (f2) was assessed using the FDA recommended approach (f2 similarity factor). The content uniformity of the innovator product was 98.39% of the labeled claim with RSD value of 1.08%, while the content of generic products ranged from 96.98% to 98.80% with RSD values of 1.24-2.19%. All the products showed no disintegration, cracks or swelling in 0.1 N HCl, except product 1, which showed complete disintegration after 20 min. However, the disintegration of all the products in phosphate buffer met USP requirements. Dissolution of tablets in 0.1 N HCl showed no drug release after 2 h except product 1 in which one tablet showed a drug release more than 10% at acid stage level A1. In addition, three tablets of this product showed dissolution of 45%, 48% and 69% at acid stage level A2. The similarity factor f2 of the products was between 71 and 74 indicating the similarity in dissolution profiles of all the products in accordance to FDA requirements, except product 1 in which f2 value was 18.67.