Liposome Solution Research Articles

Multifunctional Containers from Anionic Liposomes and Cationic Polymers/Colloids

The study describes an “open” method for concentrating anionic bilayer lipid vesicles (liposomes) locally by electrostatically binding them in a complex with cationic polymers. This method is implemented by mixing premade solutions of liposomes and polymers, which significantly reduces the time and cost of obtaining multiliposomal complexes. Binding of liposomes with cationic linear polymers, latexes, and star polymers does not solve the problem of obtaining multiliposomal complexes: the size of such complexes cannot be controlled, and these variants fail to ensure the integrity of bound liposomes or result in complexes with a minimal amount of liposomes. The best results are demonstrated by complexes of anionic liposomes and polystyrene nanoparticles with grafted cationic chains (spherical polycationic brushes). Each brush can bind several dozen liposomes, which retain their integrity after being adsorbed on the surface of the brush. Such complexes do not dissociate into the initial components either in physiological saline with [NaCl] = 0.15 mol/L or in the presence of significant amounts of protein. The use of liposomes with different fillers (different liposomal “compartments”) makes it possible to obtain multiliposomal complexes with the desired fraction of substances encapsulated in the liposomes. The proposed approach is of interest in terms of obtaining multiliposomal complexes for concentration, compartmentalization, and subsequent controlled release of drugs.

Convection enhanced delivery of liposome encapsulated doxorubicin for brain tumour therapy

Convection enhanced delivery is promising to overcome the blood brain barrier. However, the treatment is less efficient in clinic due to the rapid elimination of small molecular drugs in brain tumours. In this study, numerical simulation is applied to investigate the convection enhanced delivery of liposome encapsulated doxorubicin under various conditions, based on a 3-D brain tumour model that is reconstructed from magnetic resonance images. Treatment efficacy is evaluated in terms of the tumour volume where the free doxorubicin concentration is above LD90. Simulation results denote that intracerebral infusion is effective in increasing the interstitial fluid velocity and inhibiting the fluid leakage from blood around the infusion site. Comparisons with direct doxorubicin infusion demonstrate the advantages of liposomes in enhancing the doxorubicin accumulation and penetration in the brain tumour. Delivery outcomes are determined by both the intratumoural environment and properties of therapeutic agents. The treatment efficacy can be improved by either increasing the liposome solution concentration and infusion rate, administrating liposomes in the tumour with normalised microvasculature density, or using liposomes with low vascular permeability. The delivery is less sensitive to liposome diffusivity in the examined range (E-11~E-7 cm2/s) as convective transport is dominative in determining the liposome migration. Drug release rate is able to be optimised by keeping a trade-off between enhancing the drug penetration and providing sufficient free doxorubicin for effective cell killing. Results from this study can be used to improve the regimen of CED treatments.

Effect of silencing aquaporin 4 on learning and memory dysfunction in rats with traumatic brain injury

To observe the protein expression related to cognitive and learning memory function, and to investigate the effect of aquaporin 4 (AQP4) silence on learning and memory function in traumatic brain injury (TBI) rats. Ninety-six healthy adult male Wistar rats were divided into groups according to the random number table. (1) Forty-eight rats were divided into sham operation (sham) group, TBI group (by using modified Feeney method), AQP4 RNA interference (RNAi) negative group [TBI+meaningless small interfering RNA (siRNA)-AQP4 liposome solution 10 μL], and AQP4 RNAi group (TBI+siRNA-AQP4 liposome solution 10 μL). In each group, brain tissues of 4 rats were harvested at 1, 6 and 12 hours respectively. The protein expressions of hippocampus AQP4, general control nonderepressible 2 kinase (GCN2), cyclic adenosine monophosphate response element binding protein (CREB) and phosphorylated CREB (p-CREB) were detected by Western Blot. (2) In addition, 48 rats were divided into normal control group (control group), sham group, TBI group and AQP4 RNAi group, brain water content were measured in 6 of them after 12 hours of injury, and 6 were used in Morris water maze test. (1) The protein expressions of hippocampus AQP4 and GCN2 in TBI group were significantly higher than those in sham group, and increased gradually with time with statistical difference at 12 hours (AQP4 protein: 5.03±0.09 vs. 1, GCN2 protein: 4.01±0.13 vs. 1, both P < 0.01); the protein expressions of hippocampus CREB and p-CREB were significantly lower than those in sham group, and decreased gradually with time with statistical difference at 12 hours (CREB protein: 0.38±0.03 vs. 1, p-CREB protein: 0.38±0.03 vs. 1, both P < 0.01). Compared with TBI group, the protein expressions of AQP4 in AQP4 RNAi group was significantly decreased (1 hour: 1.02±0.04 vs. 2.23±0.05, 6 hours: 1.23±0.03 vs. 2.59±0.04, 12 hours: 2.20±0.08 vs. 5.03±0.09, all P < 0.01), but there were no significant difference in the expressions of GCN2, CREB or p-CREB. There was no significant difference in the expression of protein between AQP4 RNAi negative group and TBI group. (2) The brain water content in TBI group was significantly higher than that in control group and sham group [(83.7±0.4)% vs. (76.2±0.2)%, (76.2±0.3)%, both P < 0.01]. The brain water content in AQP4 RNAi group [(78.8±0.3)%] was significantly decreased as compared with that in TBI group (P < 0.01). The latency of Morris water maze test was significantly prolonged in the day 11, 13 and 15 after the injury of the TBI group and AQP4 RNAi group, and the exploration time was significantly shortened. Compared with TBI group, the incubation period of AQP4 RNAi group was significantly shortened at 15 days (s: 60.2±11.1 vs. 62.0±11.5, P < 0.05), and the exploration time was significantly prolonged (s: 37.0±8.5 vs. 32.7±9.2, P < 0.05). The impairment of cognitive and learning memory function in rats after TBI was significantly related to the changes in CREB and GCN2 in cognitive and learning memory function. After RNAi treatment, the cognitive and learning and memory function of rats was not improved obviously, but the brain edema could be alleviated.

Benchmarking of Sterilizing-Grade Filter Membranes with Liposome Filtration.

Cytotoxic drugs can be encapsulated in liposomes vesicles, which act as drug delivery vehicles and reduce the risk of exposure of drug to healthy cells. The sterility of such liposome solutions is typically ensured using 0.2 μm-rated sterilizing-grade membranes, but due to the high viscosity and low surface tension of these formulations, they can cause premature blocking and increased risk of bacterial penetration through a 0.2 μm sterilizing-grade membrane. The low surface tension of liposome solutions affects the contact angle with membrane and reduces bubble point, leading to bacterial penetration through the membrane. This poses a great challenge to select an appropriate sterilizing-grade membrane for a given process and for filter manufacturers to develop a sterilizing-grade membrane that specifically addresses these needs. In this study, the influence of different variables that could affect the total throughput and bacterial retention performance of different membrane types on processing of liposome solutions was evaluated. Based on the results, we conclude that the membrane properties, for example, surface porosity, surface tension, pore size, symmetry/asymmetry, hydrophilicity and liposome properties (e.g., composition, lipid size, and concentration) affect bacterial retention and total throughput capacity. Process parameters such as temperature, pressure, and flow should also be optimized to improve process efficiency.LAY ABSTRACT: Cytotoxic drugs can be encapsulated in liposomes vesicles, which act as drug delivery vehicles and reduce the risk of exposure of drug to healthy cells. Liposome solution cause premature blocking and increased risk of bacterial penetration through a 0.2 μm sterilizing-grade membrane due to their high viscosity and low surface tension. In this study, we demonstrated the total throughput and bacterial retention performance of different sterilizing-grade membranes with liposome solution. Based on the results, we conclude that some sterilizing-grade membranes yield less throughput and bacterial retention compared to other membranes. This is due to liposome formulation and membrane properties. Therefore, it is important to identify the product formulation and membrane properties before selection of a suitable sterilizing-grade filter for a given process application to ensure expected throughput and bacterial retention.

An investigation of the beam damage effect on in situ liquid secondary ion mass spectrometry analysis.

During in situ liquid secondary ion mass spectrometry (SIMS) analysis, the primary ion beam is normally scanned on a very small area to collect signals with high ion doses (1014 to 1016 ions/cm2 ). As a result, beam damage may become a concern when compared with the static limit of SIMS analysis, in which the dose is normally less than 1012 ions/cm2 . Therefore, a comparison of ion yields in in situ liquid SIMS analysis versus traditional static SIMS analysis of corresponding dry samples is of great interest. In this study, a dipalmitoylphosphatidylcholine (DPPC) liposome solution was used as a model system. Both liquid sample and dry sample were examined. Secondary ion yields using three primary ion species (Bi+ , Bi3+ and Bi3++ ) with various beam currents were investigated. Usable ion yields for both positive and negative characteristic signals (including molecular ions and characteristic fragment ions) were achievable based on optimized experimental conditions for in situ liquid SIMS analysis. The ion yield of the key DPPC molecular ion was comparable to that of traditional static SIMS, and unexpected low fragmentation was observed. The flexible structure of the liquid plays an important role for these observations. Therefore, beam damage may not be a concern in in situ liquid SIMS analysis if proper experimental conditions are used.

Study of Effectiveness of Liposomal Oral Rehydration Solutions in an Osmotic Diarrhea Model in Rats: 2017 Presidential Poster Award

Study of Effectiveness of Liposomal Oral Rehydration Solutions in an Osmotic Diarrhea Model in Rats: 2017 Presidential Poster Award

Enhanced Immune Response to Rabies Viruses by the Use of a Liposome Adjuvant in Vaccines.

Essen regimen, the Thai Red Cross two-site ID regimen, Zagreb schedule, and the eight-site ID regimen are the standard rabies vaccines recommended by the World Health Organization (WHO). In this study, a liposomal rabies vaccine (LipoRV) was developed, which was found to facilitate the production of rabies virus neutralizing antibody (RVNA) in BALB/c mice. Liposome solution was prepared with hydrogenated soya phosphatide and cholesterol. LipoRV composed of liposome solution and inactivated rabies vaccine (IRV). The immune responses were compared between the mice treated with either LipoRV or IRV. Higher levels of interleukin-2 (p < 0.05), interferon-γ (p < 0.01), and natural killer cell activity (p < 0.05) were observed in the mice immunized with LipoRV than those with IRV. The potency of LipoRV was significantly higher than that IRV (p < 0.05). In addition, three injections of LipoRV on days 0, 3, and 14 could elicit similar RVNA levels as the five shots of IRV. Our data also showed a higher survival rate in mice treated with three shots of LipoRV (56.2%) than five shots of IRV (40.6%). In conclusion, liposome enhances the immune response of mice to rabies vaccine and could be applied as a potential immunopotentiator.

Nanographene oxide as a switch for CW/pulsed NIR laser triggered drug release from liposomes

The application of pulsed and continuous wave (CW) lasers in nanomedicine has increased significantly over the last decade. Near infrared (NIR) lasers can be used for the precise control of drug release at the target site in a non-invasive manner. In this study, we have prepared nanographene oxide (nGO, size ~40nm) integrated liposomes (size ~900nm). The nGOs were not simply adsorbed onto the liposome surface but was embedded inside the liposomes as characterized by cryo-TEM, selected area electron diffraction (SAED), and fluorescence quenching studies. The embedded nGOs could act as a molecular switch for NIR light controlled drug release from the liposomes. Calcein was encapsulated into the liposome as a model drug to evaluate the efficiency of light controlled release. An on-demand pulsatile drug release was achieved by irradiation of CW/pulsed NIR lasers into the nGO-liposome suspension. Triggering with a pulsed laser resulted in larger release of calcein with a minimal temperature increase (~2°C) of the liposome solution, compared to lower release rate and a significant temperature increase (~8°C) by a CW laser with the same light energy, suggesting two separate mechanisms and different potential applications depending on the laser type.

Transversus Abdominis Plane Blocks with Single-Dose Liposomal Bupivacaine in Conjunction with a Nonnarcotic Pain Regimen Help Reduce Length of Stay following Abdominally Based Microsurgical Breast Reconstruction.

Side effects associated with use of postoperative narcotics for pain control can delay recovery after abdominally based microsurgical breast reconstruction. The authors evaluated a nonnarcotic pain control regimen in conjunction with bilateral transversus abdominis plane blocks on facilitating early hospital discharge. A retrospective analysis was performed of consecutive patients who underwent breast reconstruction using abdominally based free flaps, with or without being included in a nonnarcotic protocol using intraoperative transversus abdominis plane blockade. During this period, the use of locoregional analgesia evolved from none (control), to continuous bupivacaine infusion transversus abdominis plane and catheters, to single-dose transversus abdominis plane blockade with liposomal bupivacaine solution. Demographic factors, length of stay, inpatient opioid consumption, and complications were reported for all three groups. One hundred twenty-eight consecutive patients (182 flaps) were identified. Forty patients (62 flaps) were in the infusion-liposomal bupivacaine group, 48 (66 flaps) were in the single-dose blockade-catheter group, and 40 (54 flaps) were in the control group. The infusion-liposomal bupivacaine patients had a significantly shorter hospital stay compared with the single-dose blockade-catheter group (2.65 ± 0.66 versus 3.52 ± 0.92 days; p < 0.0001) and the control group (2.65 ± 0.66 versus 4.05 ± 1.26 days; p < 0.0001). There was no significant difference in flap loss or major complications among groups. When used as part of a nonnarcotic postoperative pain regimen, transversus abdominis plane blocks performed with single injections of liposomal bupivacaine help facilitate early hospital discharge after abdominally based microsurgical breast reconstruction. A trend toward consistent discharge by postoperative day 2 was seen. This could result in significant cost savings for health care systems. Therapeutic, III.

Adsorption kinetics of partially ionized fatty acids at oil/water interface of their monomeric and liposomal solution

Fatty acid in the partially ionized form has an astounding ability to adsorb at oil/water interface. The mechanism for adsorption of fatty acids in this condition is expected to be diffusion controlled without the presence of the adsorption barrier. Based on the existing adsorption theory, we studied the kinetics of adsorption of fatty acid at pKa environment. It was observed that both the diffusion and the kinetic (barrier) models satisfactorily described the adsorption kinetics of fatty acid monomeric solution. This behavior thus leads to a contradiction in the interpretation of results. It was observed that the contradictions could occur in the controlling mechanism, the location of the barrier, and the origination of the existence of the barrier. Herein reports the contradiction observed in the kinetics of surfactant adsorption that is often overlooked. The higher affinity of fatty acids molecule for adsorption leads to the breakdown of liposome in solution. The liposome dissociation rate constant, k, obtained from the diffusion model is increased with the increase in the liposome concentration.

Analysis of parameters of serum concentration and pharmacokinetic of liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats

The experiment was aimed to investigate the difference of plasma concentration and pharmacokinetic parameters between liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats, such as ginsenosides Rg₁, Re, Rf, Rb₁, Rg₂, Rc, Rb₂, Rb₃, Rd. After intravenous injection of liposome and aqueous solution in rats, the blood was taken from the femoral vein to detect the plasma concentration of the above 9 ginsenoside monomers in different time points by using HPLC. The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters. After the intravenous injection of ginsenosides to rats, nine ginsenosides were detected in plasma. In general, among these ginsenosides, the peak time of the aqueous solution was between 0.05 to 0.083 3 h, and the serum concentration peak of liposome usually appeared after 0.5 h. After software fitting, the aqueous solution of ginsenoside monomers Rg₁, Re, Rf, Rg₂, Rc, Rd, Rb₃ was two-compartment model, and the liposomes were one-compartment model; aqueous solution and liposome of ginsenoside monomers Rb₁ were three-compartment model; aqueous solution of ginsenoside monomers Rb₂ was three-compartment model, and its liposome was one-compartment model. Area under the drug time curve (AUC) of these 9 kinds of saponin liposomes was larger than that of aqueous solution, and the retention time of the liposomes was longer than that of the aqueous solution; the removal rate was slower than that of the aqueous solution, and the half-life was longer than that of the water solution. The results from the experiment showed that by intravenous administration, the pharmacokinetic parameters of two formulations were significantly different from each other; the liposomes could not only remain the drug for a longer time in vivo, but also reduce the elimination rate and increase the treatment efficacy. As compared with the traditional dosage forms, the total ginsenoside of ginseng stems and leaves can improve the sustained release of the drug, which is of great significance for the research and development of new dosage forms of ginsenosides in the future.

Effects of 4-hydroxyphenyl retinamide in different vehicles on the proliferation and apoptosis of human keloid fibroblasts

Objective To evaluate effects of 4-hydroxyphenyl retinamide (4-HPR) in different vehicles on the proliferation and apoptosis of human keloid fibroblasts (HKFs) . Methods A film-ultrasonic dispersion method was used to prepare 4-HPR liposome solution and 4-HPR microbubbles. Primary HKFs were in vitro treated with the 4-HPR liposome solution at different concentrations of 0-80 mg/L for 6-48 hours, and the proliferative activity of HKFs was evaluated by methyl thiazolyl tetrazolium (MTT) assay. Some other HKFs were divided into 3 experimental groups to be treated with 15 mg/L 4-HPR solution (4-HPR solution group) , 15 mg/L 4-HPR liposome solution (4-HPR liposome solution group) and 15 mg/L 4-HPR microbubbles (4-HPR microbubble group) , respectively, and each group was divided into ultrasonic-treated and -untreated subgroups. HKFs without treatment served as control group. After 24-hour treatment, MTT assay was conducted to evaluate the proliferative activity of HKFs in the above groups, flow cytometry to detect apoptosis of HKFs in all groups except the 4-HPR solution group. Results The 4-HPR liposome solution and 4-HPR microbubbles were successfully prepared. MTT assay showed inhibitory effects of 4-HPR liposome solution at concentrations of 1-80 mg/L on the proliferation of HKFs, and the proliferation inhibition rate was positively associated with the drug concentrations (r= 0.633, P < 0.01) . After the ultrasonic treatment, inhibitory effects on the proliferation of HKFs significantly differed among the 4-HPR microbubble group, 4-HPR solution group and 4-HPR liposome solution group (P < 0.01) . The 4-HPR liposome solution group and the 4-HPR microbubble group both showed significantly increased apoptosis rates (21.81% ± 3.73%, 39.79% ± 1.61%, respectively) compared with the control group (6.18% ± 0.61%, both P < 0.01) . Conclusion The 4-HPR microbubbles are successfully prepared, and 4-HPR in different vehicles all can promote HKF apoptosis and suppress HKF proliferation, among which, 4-HPR microbubbles in combination with ultrasonic treatment have stronger inhibitory effects than the 4-HPR liposome solution. Key words: Tretinoin; Keloid; Fibroblasts; Cell proliferation; 4-Hydroxyphenyl-retinamide

Characterization of the interface of binary mixed DOPC:DOPS liposomes in water: The impact of charge condensation.

Solutions of liposomes composed of binary mixtures of anionic dioleoylphosphatidylserine (DOPS) and zwitterionic dioleoylphosphatidylcholine (DOPC) are investigated with label-free angle-resolved (AR) second harmonic scattering (SHS) and electrophoretic mobility measurements. The membrane surface potential is extracted from the AR-SHS response. The surface potential changes from -10 to -145 mV with varying DOPS content ( from 0% to 100%) and levels off already at ∼ 10 % DOPS content. The ζ-potential shows the same trend but with a drastically lower saturation value (-44 mV). This difference is explained by the formation of a condensed layer of Na+ counterions around the outer leaflet of the liposome as predicted by charge condensation theories for polyelectrolyte systems.

Topical Diclofenac-Loaded Liposomes Ameliorate Laser-Induced Choroidal Neovascularization in Mice and Non-Human Primates.

This study aimed to evaluate the effect of liposomes loaded with diclofenac, a potent cyclooxygenase (COX)-1 and COX-2 inhibitor, on laser-induced choroidal neovascularization (CNV) in mice and non-human primates (common marmosets). CNV was induced by laser irradiation on the unilateral or bilateral eye of each mouse or common marmoset, respectively, under anesthesia. The CNV was visualized using fluorescence labeling with intravenous injection of fluoresceinconjugated dextran (molecular weight = 2,000 kDa), and quantified in the retinal pigment epithelia (RPE)-choroidal flatmounts. Diclofenac-loaded liposome or diclofenac ophthalmic solution was instillated to the eye surface daily for 14 days and 21 days in mice and common marmosets, respectively. In the mouse CNV model, 0.1% diclofenac-loaded liposome eye drops administered four times a day (q.i.d.) significantly reduced CNV formation in the RPE-choroidal flatmounts compared with those in empty liposome eye drops. Diclofenac-loaded liposome (0.1%) eye drops, administered once a day (s.i.d.), twice a day (b.i.d.), and three times a day (t.i.d.), also reduced CNV formation in a frequency-dependent manner. Furthermore, diclofenac-loaded liposome (0.03% and 0.1%) eye drops administered t.i.d. reduced CNV formation in a dose-dependent manner, significantly so at 0.1%. In the common marmoset CNV model, late hyperfluorescence and leakage by fluorescein angiograms was observed within or beyond the lesion borders at 17 days after laser irradiation, and diclofenac-loaded liposome eye drops (0.1% t.i.d.) tended to attenuate the late hyperfluorescence and leakage. Diclofenac-loaded liposomes had significantly reduced CNV formation in the RPE- choroidal flatmounts at 21 days after laser irradiation. In conclusion, diclofenac-loaded liposome eye drops enhance penetration to the RPE-choroid, and reduce the CNV formation. These results suggest that a drug-loaded liposome is a useful tool for drug delivery into the posterior segment of the eye.

In Vivo Microdialysis for Dynamic Monitoring of the Effectiveness of Nano-liposomes as Vehicles for Topical Psoralen Application.

In this study, the skin permeation of liposomes containing psoralen was investigated by in vivo skin microdialysis. Psoralen-loaded nano-sized liposomes were prepared with a mean size of 117.5 nm and a polydispersity index of 0.21, indicating the uniform dispersion of phosphatidylcholine vesicles in the liposomal solution. Based on in vivo microdialysis experiments, the drug concentration in local deep skin of rat increased rapidly and reached a peak concentration (Cmax) of 319.35±23.72 µg/mL at 180 min, and decreased slowly thereafter. The local area under the concentration-time curve (AUC)0-t was 3.81-fold higher than the compared aqueous suspension. The in vivo systemic pharmacokinetics were in agreement with the microdialysis results, in view of the Cmax and AUC0-t from liposomal group were both significantly higher (p<0.05) than the compared group. Liposome-associated transdermal psoralen delivery was significantly more effective than delivery via an aqueous suspension. The enhanced skin permeability may be associated with improved skin hydration, lipid exchange and fusion with the stratum corneum (SC), and changes in SC structure, promoting drug permeation into deep skin. After 10 h of treatment with the perfusate, the microstructure of the microdialysis probe exhibited no obvious differences with control probes. The skin surface and the tissue around the probe showed no swelling or inflammation. These findings indicated that liposomes effectively enhanced the skin deposition of psoralen and showed good biocompatibility with skin tissues; additionally, ethanol at a low concentration in ringer's solution is an alternative perfusate for in vivo skin microdialysis studies.

Obtaining and study of the effect of liposomal solution of the follicular chicken eggs' extract on the quality of bread

Obtaining and study of the effect of liposomal solution of the follicular chicken eggs' extract on the quality of bread

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

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.

Concentration dependence of nitroxyl spin probes in liposomal solution: electron spin resonance and overhauser-enhanced magnetic resonance studies

In this work, the detailed studies of electron spin resonance (ESR) and overhauser-enhanced magnetic resonance imaging (OMRI) were carried out for permeable nitroxyl spin probe, MC-PROXYL as a function of agent concentration in liposomal solution. In order to compare the impermeable nature of nitroxyl radical, the study was also carried out only at 2 mM concentration of carboxy-PROXYL. The ESR parameters were estimated using L-band and 300 MHz ESR spectrometers. The line width broadening was measured as a function of agent concentration in liposomal solution. The estimated rotational correlation time is proportional to the agent concentration, which indicates that less mobile nature of nitroxyl spin probe in liposomal solution. The partition parameter and permeability values indicate that the diffusion of nitroxyl spin probe distribution into the lipid phase is maximum at 2 mM concentration of MC-PROXYL. The dynamic nuclear polarization (DNP) parameters such as DNP factor, longitudinal relaxivity, saturation parameter, leakage factor and coupling factor were estimated for 2 mM MC-PROXYL in 400 mM liposomal dispersion. The spin lattice relaxation time was shortened in liposomal solution, which leads to the high relaxivity. Reduction in coupling factor is due to less interaction between the electron and nuclear spins, which causes the reduction in enhancement. The leakage factor increases with increasing agent concentration. The increase in DNP enhancement was significant up to 2 mM in liposomal solution. These results paves the way for choosing optimum agent concentration and OMRI scan parameters used in intra and extra membrane water by loading the liposome vesicles with a lipid permeable nitroxyl spin probes in OMRI experiments.

Changes in levels of cytokines in the treatment of infected wounds and festering in children

Informative and prognostic significance of cytokines in assessing the effectiveness of treatment tactics no doubt. The aim was to study the levels of pro- and anti-inflammatory cytokines in the dynamics of the treatment of infected wounds and purulent (IWP) in children using the proposed optimized local treatment compared with standard procedure. Materials and methods. 45 children with IWP who were treated in the department of purulent surgery of Zaporozhye Regional Children's Hospital during the period of 2015-2016 years were divided into main (n = 26) and control groups (n = 19) depending on the tactics of treatment. The therapy of the main group patients were added by optimized integrated local treatment, which included a combination of magnetic therapy, antibacterial drug liposomal solutions and hirudotherapy. Efficacy of treatment was assessed by clinical characteristics and serum levels of IL-1β and IL-10 on the 1 st and the 7 th day of treatment. Results. The highest levels of pro-inflammatory IL-1β were defined in children with lymphadenitis on the first day of treatment. Common trends in the dynamics of cytokines content changes on the 7 th day were in the line with generally accepted: decreased in IL-1β and increased in IL-10 levels. The level of IL-1β was not statistically different on the 7 th day only in children with phlegmon. The most significant changes in IL-10 were observed in children with abscesses and lymphadenitis than in children with infected wound and phlegmon. Changes in markers of inflammation conform to positive changes in the clinical course of wound healing in children at the study. Generally, there was a lag dynamics of cytokines changes in the children who received standard therapy compared with the children who received the proposed optimized local treatment. Conclusions. The use of proposed IWP complex treatment in children showed the most significant effect on the anti-inflammatory IL-10 level in children with abscesses and lymphadenitis. Serum level of IL-1β and IL-10 can not be used to assess the dynamics of wound healing in children with phlegmon.

Tissue distribution of galactosyl daphnoretin liposomes in rats

To study the tissue distribution of galactosyl daphnoretin liposomes in rats. At the dose of 10 mg•kg⁻¹, daphnoretin solution, daphnoretin liposomes, and galactosyl daphnoretin liposomes were administered to healthy SD rats via tail vein injection. The blood and tissue of heart, liver, spleen, lung, kidney, stomach, small intestine, brain and thymus were collected at 5, 15, 30, 45, 60, 120, 240, 360 min after administration. The concentrations of daphnoretin in plasma and tissue samples were determined by HPLC. The results showed that galactosyl daphnoretin liposomes group had the highest concentration of daphnoretin in liver of unit weight at different time points; and at all of the time points, the target index DTI values of galactosyl daphnoretin liposomes to liver were greater than that of daphnoretin liposomes. Compared with daphnoretin solution, the AUC0-6 and Cmax of galactosyl daphnoretin liposomes in liver were 2.23, 5.22 times, respectively. This indicated that galactosyl daphnoretin liposomes can be concentrated at liver, with a significant liver targeting effect.