FORMULATION THERMORESPONSIVE NANOCOMPOSITE HYDROGELWITH EMBEDDED PLGA NANOPARTICLES CONTAINING CYTOTOXIC AGENT.

The aim of the study was to develop and characterize the nanocomposite in-situ hydrogel as local drug delivery system of cytotoxic agent. In-situ hydrogel consisting of 15% thermosensitive (Poloxamer 407) and 1% mucoadhesive (sodium alginate) polymers was selected as the optimal formulation by the conducted studies. The influence of nanoparticle concentration on gelation time and temperature has been experimentally established. As a result, the optimum concentration of nanoparticles (5%) is selected, which does not alter the gel forming process. The resulting nanocomposite hydrogel was characterized through Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), rotational viscometer (LVDV-1T). FT-IR spectra confirmed the PLGA nanoparticles presence within the hydrogel matrix through the absorption peak located at 1750 cm-1. SEM images allowed observing the nanoparticles to be homogenously dispersed. The release pattern of the active substance from the nanocomposite hydrogel is following: at 72 h, 64% and 78% of the active substance were released into the phosphate buffer and cell culture area, respectively. Irritation test on hen's egg model revealed that formulated nanocomposite hydrogel did not show damage of vascular system.

BIOPHARMACEUTICAL UNDERSTANDING OF FORMULATION PREPARATION VARIABILITY OF PLGA NANOPARTICLES LOADED WITH ERYSIMUM EXTRACT.

The purpose of this study was to evaluate effect of process and formulation variables on the preparation of Erysimum extract loaded PLGA nanoparticles. The influence of the various biopharmaceutical factors such as type of organic solvent, type and concentration of surfactant, polymer concentration in the organic phase, ratio of organic phase and water phase were studied. Modified emulsification solvent evaporation method was used for preparation of nanoparticles. Based on the performed experiments optimal formulation of nanocomposite is suggested. Nanoparticle size, size distribution and entrapment efficiency were determined. Among five non-ionic surfactants polyvinyl alcohol provided more stable nanocomposite. Influence mechanisms of different surfactants on nanoparticle formation are provided. Water miscible organic solvent, acetone obtained 232 nm nanoparticles with improved size distribution. Entrapment efficiency was increased to 73% by reducing ratio of organic and water phases. Based on experiments nanoparticles with stable, reproducible properties are fabricated.

FORMULATION OF BIODEGRADABLE POLYMERIC NANOPARTICLES CONTAINING CYTOTOXIC SUBSTANCE OF PLANT ORIGIN.

Formulation of novel drug delivery system is one of the approaches for improvement of pharmacological activity of drugs. This implies encapsulation of the API into the biocompatible polymeric material. Objective of the research was formulation of biodegradable amino acid based polyesteramide nanoparticles composing cytotoxic substance of plant origin. Research materials and methods: biodegradable polyesteramide (PEA), alkaloids from Vinca Minor, surfactants (Tween 80, polyvinyl pirolidone, polyvinyl alcohol, Poloxamer 188). NPs size (mean particle diameter) and size distribution (polydispersity index, PDI), and zeta-potential (ZP) were measured by dynamic light scattering (DLS) using a Zetasizer Nano ZS (Malvern Instruments, U.K.) at 25°C, UV spectrophotometer was used for %EE study. Amino acid based PEA particles were fabricated by the modified emulsification method. Based on the studies optimal composition and fabrication condition of PEA NPs was determined. The conditions of the NPs fabrication were as follows: the O/W ratio: 1:10; the solvent: DMSO; polymer concentration in the organic phase: 50.0 mg/mL; surfactants (PVA) concentration in aqueous phase 0.5%,the stirring rate: 1000 rpm. The influence of the various factors such as organic solvents, surfactants, as well as a polymer concentration in the organic phase,surfactant concentration in the aqueous phase,the organic/water phase ratio on the NPs fabrication was studied.The NPs were characterized by size (mean particle diameter & size distribution (polydispersity index, PDI), and zeta-potential (ZP). Increase concentration of the surfactant (polyvinyl alcohol) from 0.1% to 0.5% decrease average particle size from 568±63 to 169±1.66 respectively. EE% was obtained to be around 50%.

Identifying latent tuberculosis in high-risk populations: systematic review and meta-analysis of test accuracy.

BACKGROUND: The relative accuracy of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) in identifying latent tuberculosis infection (LTBI) is uncertain.OBJECTIVE: To perform a systematic review and meta-analysis to compare the sensitivity and specificity of IGRAs and TST for the prediction of progression to clinical tuberculosis (TB).METHODS: We searched electronic databases (e.g., MEDLINE and EMBASE) from December 2009 to September 2018 for prospective studies that followed up individuals who had undergone testing with commercial IGRAs and/or TST but had not received treatment based on the test result. The sensitivity and specificity estimates were pooled using a Bayesian bivariate random-effects model.RESULTS: Twenty-five studies, mostly with moderate to high risk of bias and a mean follow-up time ranging from 1 to 5 years were included. TST (10-15 mm) tended to have lower sensitivity and higher specificity than QuantiFERON® Gold In-Tube, T-SPOT®.TB and TST (5 mm). The evidence did not indicate that any test outperformed the others due to wide and overlapping 95% credible intervals.CONCLUSION: The evidence following individuals who had undergone testing for LTBI and had progressed to clinical TB is sparse. We did not find that IGRAs were superior to TST or vice versa; however, as our findings are based on a small number of studies with methodological limitations and great uncertainty around the pooled estimates, the results should be interpreted with caution.

EXTRACTION AND CHARACTERIZATION OF HUMIC SUBSTANCES FROM SPHAGNUM PEAT PELOIDS.

The objective of the research was development extraction process of humic substances from sphagnum peat peloids, selection of extragent and characterization of humic substances. The objects of the research: Kolkheti peat peloids (Ispani, Anaklia, Churia, Chirukhi, Peranga) of different formation phases. Research was held using modern instrumental methods of analysis: UV spectrophotometer, Scanning Electron Microscopy, Centrifuge, Dry oven, Ultraturax. In the research extraction process of humic substances from sphagnum peat peloids was developed and composition of humic substances was studied, also E4/E6 humification coefficient was evaluated. Based on the results extraction conditions of humic substances from the peat peloids samples were determined: a) extragent with maximum yield - 1.0N NaOH; b) mixing type - KA-ULTRA TURAX-T18 - 20 000 rpm/min; c) Precipitant of humic substances -10% HCL. Composition of humic substances are studied in the samples and their relatively high content is determined in Anaklia and Churia sphagnum peat peloids. For characterization of humic substances E4/E6 humification coefficient was evaluated. Low ration of E4/E6 < 5 was established in anaklia, churia and ispani peat peloids. High ration of E4/E6 < 10 coefficient is determined in chirukhi and peranga peat peloids.

When and how to update systematic reviews.

BACKGROUND: Systematic reviews are most helpful if they are up-to-date. We did a systematic review of strategies and methods describing when and how to update systematic reviews. OBJECTIVES: To identify, describe and assess strategies and methods addressing: 1) when to update systematic reviews and 2) how to update systematic reviews. SEARCH STRATEGY: We searched MEDLINE (1966 to December 2005), PsycINFO, the Cochrane Methodology Register (Issue 1, 2006), and hand searched the 2005 Cochrane Colloquium proceedings. SELECTION CRITERIA: We included methodology reports, updated systematic reviews, commentaries, editorials, or other short reports describing the development, use, or comparison of strategies and methods for determining the need for updating or updating systematic reviews in healthcare. DATA COLLECTION AND ANALYSIS: We abstracted information from each included report using a 15-item questionnaire. The strategies and methods for updating systematic reviews were assessed and compared descriptively with respect to their usefulness, comprehensiveness, advantages, and disadvantages. MAIN RESULTS: Four updating strategies, one technique, and two statistical methods were identified. Three strategies addressed steps for updating and one strategy presented a model for assessing the need to update. One technique discussed the use of the "entry date" field in bibliographic searching. Statistical methods were cumulative meta-analysis and predicting when meta-analyses are outdated. AUTHORS' CONCLUSIONS: Little research has been conducted on when and how to update systematic reviews and the feasibility and efficiency of the identified approaches is uncertain. These shortcomings should be addressed in future research.