Influence of doxorubicin inclusion into phospholipid nanoformulation on its antitumor activity in mice: increased efficiency for resistant tumor model

Aim: The new formulation of doxorubicin on the base of phospholipid nanoparticles (particle size <30 nm) is elaborated in the Institute of Biomedical Chemistry (Russian Academy of Medical Sciences) on the base of plant phospholipids. The aim of study is to investigate an antitumor effect of this nanoformulation in mice with two cancer models with various sensitivity to chemotherapy — lymphoid malignancy P-388 and Lewis lung carcinoma (LLC). Methods: Nanophospholipid (NPh) formulation of doxorubicin was prepared by homogenization of soybean phosphatidylcholine and doxorubicin hydrochloride. The effect of this formulation was studied in experiments with single or threefold drug administration. Percents of tumor growth inhibition in mice under influence of free or NPh doxorubicin forms were compared. Results: Single administration of both free and NPh doxorubicin in mice with P-388 resulted in the same quick severe inhibition of tumor growth (60–90% depending from dose), with further gradual decrease of inhibition degree. However for more resistant tumor, LLC, the obvious advantage of NPh doxorubicin form was shown. The little effect of free doxorubicin began to reveal only after 11 days, but NPh formulation induced significant inhibition of tumor growth (40%) from the first experimental point (6 days after administration). The advantages of NPh doxorubicin was manifested particularly in low drug doses, 2 and 4 mg/kg. In other experiment design in mice with LLC, with threefold weekly drug administration, NPh doxorubicin appeared to be 2.5 times more active than free drug. The reason of the same actions of free and NPh doxorubicin form in P-388 is suggested the high drug sensitivity of this model, that gives quick high drug response for any doxorubicin form. Conclusion: Doxorubicin in phospholipids nanoformulation revealed higher antitumor efficiency as compared with free doxorubicin in mice with LLC carcinoma. The mechanism of such changes is supposed to be caused by increase of doxorubicin availability for cancer cells

НАНОЧАСТИЦЫ КАК СИСТЕМЫ ТРАНСПОРТА ДЛЯ ПРОТИВОТУБЕРКУЛЕЗНЫХ ЛЕКАРСТВ

The increase of tuberculosis incidence in last decade stimulated elaboration of both new antituberculous drugs and also searches of optimizing delivery systems for existing drugs. It is determined by their side effects and low bioavailability of effective first line  drug rifampicin. Various nanosystems for transport of antituberculous drugs are considered on the basis of various polymers, liposomes, lipid nanoparticles, nanoemulsios, nanosuspensions, dendrimers, cyclodextrines. Influence of drug incorporation into nanoparticles, most often for rifampicin, on pharmacokinetics and efficiency in tuberculosis models is discussed. The most of works are devoted to polymer nanoparticles for oral administration where increased circulation time and efficiency were shown. The best results were observed after drug inclusion into solid lipid nanoparticles. The liposomes formulations were investigated mostly for inhalation and injection administrations. Positive results were also observed. Authors underline the viability of incorporation of antituberculous drugs into phospholipid nanoparticles that may increase intestinal absorption and bioavailability. It is confirmed by authors’ own data that showed increase of rifampicin efficiency after their incorporation into such nanoparticles. Повышение частоты заболеваемости туберкулезом в последние годы стимулировало разработки новых противотуберкулезных препаратов, а также способов повышения эффективности уже имеющихся средств с использованием различных систем транспорта.  Это обусловлено побочными реакциями и низкой биодоступностью одного из наиболее эффективных противотуберкулезных препаратов 1-го ряда рифампицина. В обзоре рассмотрены различные системы транспорта противотуберкулезных препаратов на основе полимеров, липосом, липидных наночастиц, дендримеров, циклодекстринов, наноэмульсий. Приведены данные по влиянию включения лекарств (чаще всего — рифампицина) в наночастицы на их фармакокинетику и противотуберкулезную активность. Наибольшее число работ посвящено полимерным наночастицам, вводимым перорально: показано увеличение времени циркуляции и активности включенных противотуберкулезных препаратов. Более высокая эффективность наблюдалась при использовании твердых липидных наночастиц. Для ингаляционного или инъекционного введения исследовали в большей степени влияние липосомальных форм, также показавших положительные результаты. Отмечена перспективность встраивания противотуберкулезных препаратов в наночастицы на основе фосфолипидов, и приведены собственные данные авторов о повышении эффективности рифампицина при встраивании в такие наночастицы.

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Searches for electroweak neutralino and chargino production in channels with Higgs, Z, and W bosons in pp collisions at 8 TeV

Searches for supersymmetry (SUSY) are presented based on the electroweak pair production of neutralinos and charginos, leading to decay channels with Higgs, Z, and W bosons and undetected lightest SUSY particles (LSPs). The data sample corresponds to an integrated luminosity of about 19.5 fb(-1) of proton-proton collisions at a center-of-mass energy of 8 TeV collected in 2012 with the CMS detector at the LHC. The main emphasis is neutralino pair production in which each neutralino decays either to a Higgs boson (h) and an LSP or to a Z boson and an LSP, leading to hh, hZ, and ZZ states with missing transverse energy (E-T(miss)). A second aspect is chargino-neutralino pair production, leading to hW states with E-T(miss). The decays of a Higgs boson to a bottom-quark pair, to a photon pair, and to final states with leptons are considered in conjunction with hadronic and leptonic decay modes of the Z and W bosons. No evidence is found for supersymmetric particles, and 95% confidence level upper limits are evaluated for the respective pair production cross sections and for neutralino and chargino mass values

Approbation of the Russian-language version of the Barratt Impulsiveness Scale (BIS-11)

The results of approbation of the Russian-language version of the questionnaire measure of impulsivity "Scale of the Barratt Impulsivity" (BIS-11). Demonstrated reliability and validity obtained the Russian version of the questionnaire. The study involved 200 people (among them 50 patients of the hospital). Assessment of validity was conducted by comparing the results with the results of the following methods: questionnaire of the I7 – Impulsiveness, (7-I version. A. Eysenck, S. Eysenck. Adaptation of the T. V. Kornilova, A. A. Dolnikova), 16 LF (Cattell). Correlation analysis of the scale of the Questionnaire with specific scales overall personality Questionnaire 16 PF and Kettell special I7 Impulsiveness Questionnaire Eysenck showed that the construct validity of the Questionnaire BIS-11 overall confirmed. It is shown that people with personality disorders (mainly psychopathy), Impulsivity Scale the Barratt have the level of impulsivity is significantly higher than the group norms. The results of the study allow to recommend the Russian version of the questionnaire BIS-11 for use in clinical diagnostics, in the field of training and education to determine proficiency

Investigation of Volatile Organic Compounds and Benzo[a]pyrene Contents in the Aerosols of Cigarettes and IQOS Tobacco Heating System Using High-Performance Gas Chromatography/Mass Spectrometry

The aim of the research was to compare the content of tobacco smoke obtained from five cigarette brands, 3R4F reference cigarette, and emission derived from IQOS tobacco heating system (Technical regulations of Customs Union “Technical regulations for tobacco products” (TP TC 035/2014) http://www.eurasiancommission.org/ru/act/texnreg/deptexreg/tr/Pages/tabac.aspx Accessed 5 August 2021). Constituents of the IQOS tobacco heating system stick aerosol, mainstream smoke of five commercial cigarettes, and 3R4F reference cigarette smoke were tested. The list of toxicants that are relevant to human health risks and appear on lists of priority toxicants in cigarette smoke was selected. Nicotine, carbon monoxide, 1,3-butadiene, benzene, and benzo[a]pyrene contents were measured using gas chromatography/mass spectrometry methods. Most of the analyzed compounds were detected in the IQOS mainstream aerosol at a significantly lower level than in smoke of the 3R4F reference cigarette and commercial cigarettes. The nicotine content decreased in IQOS mainstream aerosol by 33.7–40.3% compared to 3R4F reference cigarettes and by 42.7% compared to cigarette brands. The yields per puff were similar to the data published by the PMI tobacco company (Schaller et al. in Regul Toxicol Pharmacol 81:S27-S47, 11) and independent laboratories (Li et al. in Nicotine Tob Res 21:111–118, 12; Mallock et al. in Arch Toxicol 92: 2145, 13). Our results showed that the content of priority toxic compounds indicated in the WHO/FDA and Health Canada lists (carbon monoxide, 1,3-butadiene, benzene, and benzo[a]pyrene) and nicotine was significantly lower in case of IQOS tobacco stick aerosol than in the smoke of the 3R4F reference and commercial cigarettes. So our study represents one of the few independent studies on THS products showing similar data on aerosol emissions to those showed by the tobacco industry