scholarly journals FEATURES OF THE TECHNOLOGY OF LIPOSOMAL FORMULATION OF A ANALOGUE HYPOTHALAMIC HORMONE SOMATOSTATIN

2016 ◽  
Vol 15 (4) ◽  
pp. 78-84
Author(s):  
E. V. Sanarova ◽  
Zhang Xi ◽  
M. V. Dmitrieva ◽  
A. V. Lantsova ◽  
O. L. Orlova ◽  
...  

Background. In connection with the prospect of the use of an analog of the hypothalamic hormone somatostatin synthesized by the laboratory of chemical synthesis Institute of experimental diagnostics and chemotherapy of FSBI «N.N. Blokhin Russian Cancer Research Center» and showed a high anti-tumor activity as a drug arises a need to establish an optimal technology of its receipt. In preliminary studies in a modelformulation for an analog of the hypothalamic hormone somatostatin selected liposome technological process of which has a series of specific steps comprising. Objective. Development of technology for obtaining liposomal formulation hypothalamic hormone somatostatin analogue. Materials and methods. Liposomes analog of the hypothalamic hormone somatostatin obtained by method Bengema in modification for hydrophobic substances. To reduce the diameter of the liposome are used methods extrusion, homogenization and ultrasonic. Analysis of the size of the liposomes was performed by correlation spectroscopy light scattering using nanosizer. The pH of the liposomal dispersion was determined by potentiometry. The quantitative content of the drug substance was determined by spectrophotometry using a standard sample with X (282 ± 3) nm and an alcoholic solution of empty liposomes as a reference solution. Amount of incorporated drug was calculated as the ratio of the concentration of drug in the liposome dispersion after filtration to the concentration of drug in the dispersion after preparation. Results and Conclusion. The hydrophobic nature of the substance causes an analog of the hypothalamic hormone somatostatin technological features of obtaining liposomal formulation. Since the step of forming a film of the lipid substance is dissolved in an organic solvent together with lipids, film is hydrated by a solution of cryoprotectant. Grinding liposomes an analog of the hypothalamic hormone somatostatin appropriate to be carried out using homogenization or extrusion methods, due to the high efficiency of these methods, the preservation stability of the liposomes and a high percentage of inclusion an analog of the hypothalamic hormone somatostatin, included in the liposomal bilayer. At the stage of separating the non-inclusion of substance an analog of the hypothalamic hormone somatostatin due to the insolubility of the substance in the water, you can use the filtering method, without the need for complicated procedures gel filtration, dialysis, etc. Furthermore the process of separating a substance not included can be combined with the sterilization of the liposome dispersion by selecting a particular filter material.

2015 ◽  
Vol 14 (4) ◽  
pp. 73-78
Author(s):  
E. V. Sanarova ◽  
A. V. Lantsova ◽  
Xi Zhang ◽  
M. V. Dmitrieva ◽  
A. P. Polozkova ◽  
...  

At present, the hormone somatostatin analogues is increasing interest in connection with their activity against hormone-dependent tumors, which leads to the need to develop domestic drugs belonging to this group. In the laboratory of chemical synthesis Institute of experimental diagnostics and chemotherapy of FSBI «N.N. Blokhin RCRC» synthesized new domestic pentapeptide somatostatin analogue of hypothalamic hormone (AGGS). In preliminary studies of this substance demonstrated sufficiently high antitumor activity AGGS on transplanted solid tumors of mice. Due to the insolubility of the substance in the water as an alternative liposomal formulation proposed, allowing to increase the bioavailability of the drag due to the possibility of intravenous administration, increased therapeutic efficacy and reduce side effects, by improving the selectivity of action against tumor cells. During experiments on the development of the liposomal formulation AGGS pre-established model containing as essential components of the liposomal bilayer and egg lecithin PEG-2000-DSPE in a molar ratio 72/1 and as a ciyo- protectant - sucrose. In developing the technological parameters of the process of obtaining dosage form (LF) found that for an acceptable size derived phosphohpid vesicles needs about 7 cycles extrusion. The lack of stability of liposomal dispersion selected composition during storage has led to this problem by means of freeze-drying, which kept the physico-chemical parameters LF at the initial level. The efficacy of the model LF on transplantable tumors of mice - breast adenocarcinoma Ca-755, which was more than 60 % of ITG at a dose of 5 mg / kg and more than 80 % ITG with 20 mg / kg. The findings of biological experiments indicate the prospects for further research and improvement liposomal LF to produce high-performance domestic anticancer drag from the group of somatostatin analogues.


1990 ◽  
Vol 63 (03) ◽  
pp. 499-504 ◽  
Author(s):  
A Electricwala ◽  
L Irons ◽  
R Wait ◽  
R J G Carr ◽  
R J Ling ◽  
...  

SummaryPhysico-chemical properties of recombinant desulphatohirudin expressed in yeast (CIBA GEIGY code No. CGP 39393) were reinvestigated. As previously reported for natural hirudin, the recombinant molecule exhibited abnormal behaviour by gel filtration with an apparent molecular weight greater than that based on the primary structure. However, molecular weight estimation by SDS gel electrophoresis, FAB-mass spectrometry and Photon Correlation Spectroscopy were in agreement with the theoretical molecular weight, with little suggestion of dimer or aggregate formation. Circular dichroism studies of the recombinant molecule show similar spectra at different pH values but are markedly different from that reported by Konno et al. (13) for a natural hirudin-variant. Our CD studies indicate the presence of about 60% beta sheet and the absence of alpha helix in the secondary structure of recombinant hirudin, in agreement with the conformation determined by NMR studies (17)


1998 ◽  
Vol 3 (2) ◽  
pp. 65-78 ◽  
Author(s):  
Gwangpyo Ko ◽  
Harriet A. Burge ◽  
Michael Muilenberg ◽  
Stephen Rudnick ◽  
Melvin First

Mycobacterium tuberculosis (MTB) is transmitted through the air, and can be captured on ventilation air filters. People handling these filters may be exposed to infectious material. We studied the survival of strains of Mycobacterium on high efficiency particulate air (HEPA) filter material. We used a model ventilation system to evaluate survival over time of Mycobacterium chelonae and H37Ra (an avirulent stain of MTB) aerosolized and then captured on HEPA filter material. Survival curves for M. chelonae incubated at 55% and 75% RH under static conditions were not different with less than 4% survival at 24 hours. H37Ra was subjected to continuous airflow at the design airflow for the filter material following deposition on the HEPA filter material, and less than 0.1% of cells survived to 48 hours (RH not controlled). H37Ra was resistant to immobilized biocide (trimethoxysilylpropyl dimethyloctadecyl ammonium chloride) on HEPA filter material as well as the same biocide in solution. Finally, survival of H37Ra and virulent MTB strain (H37Rv) were not different following deposition onto HEPA filter material from liquid suspension and incubation under static conditions.


1992 ◽  
Vol 262 (6) ◽  
pp. G1007-G1014 ◽  
Author(s):  
N. Tahiri-Jouti ◽  
C. Cambillau ◽  
N. Viguerie ◽  
C. Vidal ◽  
L. Buscail ◽  
...  

A phosphotyrosyl protein phosphatase (PTPase) activity has been characterized in the plasma membranes of confluent AR42J pancreatic tumor cells using 32P-labeled poly(Glu, Tyr) as substrate. Membrane PTPase activity exhibited an apparent Michaelis constant of 3 microM and an apparent maximal velocity of 0.9 nmol.min-1.mg-1. It was inhibited by orthovanadate, zinc, poly(Glu,Tyr) and was stimulated by EDTA and dithiothreitol. Gel filtration of solubilized plasma membranes gave a peak of enzyme activity at a relative molecular weight of 70,000. Plasma membrane PTPase activity was changed during AR42J cell growth. At the beginning of culture, the control PTPase activity was minimal. Over the 5 days of culture, PTPase activity increased to reach a maximum (3.5-fold over control activity) preceding confluency by 2 days. Then the high level of PTPase activity was sustained until confluency. Incubation of the cells with the stable somatostatin analogue SMS 201-995 (SMS) resulted in a rapid and transient activation of crude membrane PTPase activity. Activation reached a maximum level within 5 min of addition and return to control levels within 20 min. The effect of SMS was dose dependent with half-maximal and maximal activation occurring at 6 pM and 0.1 nM SMS respectively.


2010 ◽  
Vol 152-153 ◽  
pp. 1519-1524 ◽  
Author(s):  
Jing Quan Yang ◽  
Zheng Wang ◽  
Jin Hui Wu ◽  
Li Mei Hao ◽  
Tao Tian ◽  
...  

Use of an air filter material combined with antibacterial agents is one of the most effective methods to resolve the problem of air filter contaminated by pathogenic microbes. ε-Polylysine and Natamycin are two biogenic antimicrobials that have been widely applied in recent years because of their high antibacterial efficiency, harmlessness to human body and environmental friendliness. In this paper, a novel antibacterial air filter material was prepared by immobilizing ε-Polylysine and Natamycin onto fiberglass high efficiency air filter media by acrylate adhesive bonding. The mechanical properties, aerosol filtration properties, and antibacterial properties were then evaluated. An improvement in the mechanical properties of the material prepared was seen compared to the untreated filter media. The filtration efficiency of the material prepared for particle aerosols and bioaerosols both greater than 99.997%. Antibacterial efficiency of the material prepared against Staphylococcus aureus and Escherichia coli in suspensions were both greater than 99.99% compared to the untreated filter media. The anti-mildew effect against Aspergillus niger in suspension was strong compared to the untreated filter media. Antibacterial efficiency of the material prepared against bacteria in bioaerosols was greater than 99.99%. Observed with Scanning Electron Microscope, most bacteria on antibacterial filter media appeared to be dead. Thus, antibacterial air filter material prepared by immobilizing bio-antimicrobials on fiberglass had a strong inhibitory effect against gram-positive bacteria, gram-negative bacteria and fungi, with no impairment of the intrinsic properties. This kind of material appears to be promising for application in air cleaning and biological protection fields.


2012 ◽  
Vol 393 (10) ◽  
pp. 1193-1200 ◽  
Author(s):  
Yoji Murakami ◽  
Yoshihiro Wada ◽  
Hidetomo Kobayashi ◽  
Atsushi Irie ◽  
Makoto Hasegawa ◽  
...  

Abstract ASP is a serine protease secreted by Aeromonas sobria. ASP cleaves various plasma proteins, which is associated with onset of sepsis complications, such as shock and blood coagulation disorder. To investigate a host defense mechanism against this virulence factor, we examined the plasma for ASP inhibitor(s). Human plasma inhibited ASP activity for azocasein, which was almost completely abolished by treating plasma with methylamine, which inactivates α2-macroglobulin (α2-MG). The ASP-inhibitor complex in ASP-added plasma was not detected by immunoblotting using anti-ASP antibody; however, using gel filtration of the plasma ASP activity for an oligopeptide, the ASP substrate was eluted in the void fraction (Mw>200 000), suggesting ASP trapping by α2-MG. Indeed, human α2-MG inhibited ASP azocaseinolytic activity in a dose-dependent manner, rapidly forming a complex with the ASP. Fibrinogen degradation by ASP was completely inhibited in the presence of α2-MG. α1-Protease inhibitor, antithrombin, and α2-plasmin inhibitor neither inhibited ASP activity nor formed a complex with ASP. Surprisingly, ASP degraded these plasma serine protease inhibitors. Thus, α2-MG is the major ASP inhibitor in the human plasma and can limit ASP virulence activities in A. sobria infection sites. However, as shown by fluorescence correlation spectroscopy, slow ASP inhibition by α2-MG in plasma may indicate insufficient ASP control in vivo.


2015 ◽  
Vol 72 (9) ◽  
pp. 1588-1593
Author(s):  
Chunbiao Li ◽  
Meng Li ◽  
Xiaoyan Zhang

Recently, oily wastewater treatment has become a hot research topic across the world. Among the common methods for oily wastewater treatment, coalescence is one of the most promising technologies because of its high efficiency, easy operation, smaller land coverage, and lower investment and operational costs. In this research, a new type of ceramic filter material was chosen to investigate the effects of some key factors including particle size of coarse-grained materials, temperature, inflow direction and inflow velocity of the reactor. The aim was to explore the optimum operating conditions for coarse-graining. Results of a series of tests showed that the optimum operating conditions were a combination of grain size 1–3 mm, water temperature 35 °C and up-flow velocity 8 m/h, which promised a maximum oil removal efficiency of 93%.


1986 ◽  
Vol 238 (3) ◽  
pp. 691-699 ◽  
Author(s):  
J Pen ◽  
J Van Beeumen ◽  
J J Beintema

Antibodies raised against esterase-4 and esterase-5 from Drosophila mojavensis were coupled to Protein A-Sepharose CL-4B to prepare high-efficiency immunomatrices used for their purification. Final purification was achieved by anion-exchange h.p.l.c., in the case of esterase-5 followed by gel-filtration h.p.l.c. The resultant esterase preparations were homogeneous, as judged by gel-filtration h.p.l.c., SDS/polyacrylamide-gel electrophoresis and non-denaturing gel electrophoresis. Esterase-4 and esterase-5 are the products of a duplicated gene. They are differently localized in the insect's body and expressed in different periods during development. Although both enzymes exhibit little immunological cross-reactivity, their amino acid compositions show few significant differences and their N-terminal sequences are largely identical, which clearly show their common origin.


1985 ◽  
Vol 100 (2) ◽  
pp. 652-657 ◽  
Author(s):  
R G Painter ◽  
K N Prodouz ◽  
W Gaarde

Triton X-100-insoluble residues, or skeletons, of plasma membrane-rich vesicles obtained from unstimulated human platelets were isolated by high speed centrifugation. About 10-15% of the total surface iodinatable glycoproteins IIb and III (GPIIb and GPIII, respectively) co-isolated with the insoluble fraction. After sonication and centrifugation the solubilized material was further purified by affinity chromatography on Lens culinaris lectin-Sepharose. SDS PAGE analysis of this material revealed the presence of at least three major proteins, which were shown to be GPIIb, GPIII, and membrane actin, as judged by their electrophoretic properties and on the basis of immunological criteria. Antibodies directed against platelet surface glycoproteins and antibodies directed against rabbit actin were able to immunoprecipitate all three proteins, which indicates that they were noncovalently associated with one another. Gel filtration of the Lens lectin-purified Triton-insoluble complex on Ultrogel AcA 22 showed that greater than 85% of the total surface GPIIb and III was associated with an actin-rich peak that eluted in the void volume. In contrast, the form of GPIIb-III present in the Triton-soluble membrane fraction behaved as monomeric species when chromatographed under identical conditions. Finally, the GPIIb-III membrane actin complex bound with high efficiency to rabbit f-actin in vitro in a Ca++-independent manner, whereas the monomeric forms found in the Triton-soluble fraction did not bind to actin. These results indicate that two forms of GPIIb and III exist: one that binds directly to endogenous membrane actin and one that does not.


2011 ◽  
Vol 335-336 ◽  
pp. 411-414 ◽  
Author(s):  
Yu Tian ◽  
Yun Liang ◽  
Yan Cui ◽  
Zeng Zhang

Abstract. The nanofiber based filtering material, made up of fibers of diameter less than 1000 nm, have been discovered as new filtering material for effective filtrations. Lyocell fiber is a kind of regenerated fiber which can be easily fibrillated and brought no negative impact on the recovery of filter material.The present study focuses on how the Lyocell fiber changes with the intensity of beating and compares the effect of nano-fibrillated Lyocell fiber(61°SR) and micro glass fiber(44°SR) on the properties of filter material. The results show that the length, diameter, distortion and degree of fibrillation of Lyocell fiber changes obviously by beating, and a mass of nano-fibril appeared after intensive beating. At the same time, the air permeability and pore size distribution is similar when the content of fibrillated Lyocell fiber and micro glass fiber are the same in filter material; What’s more, the strength of filter material increases with the percentage of fibrillated Lyocell fiber increasing, But the micro glass gets an opposite trend. The burst strength of the filter material with 20 wt.% fibrillated Lyocell fiber is 336KPa, with 20 wt.% micro glass fiber is 71KPa.This study has shed some light on the application of Lyocell fiber to improve the accuracy of filter material effectively.


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