scholarly journals Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1713
Author(s):  
Gennara Cavallaro ◽  
Carla Sardo ◽  
Emanuela Fabiola Craparo ◽  
Gaetano Giammona

Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt% on the total mixture, named EP-ICONs. It was seen that the ability of the INU-IMI-DETA-EGF/INU-IMI-DETA-PEG polymeric mixture to complex siGL3 increases with the increase in the EGF-based component in the EP-ICONs and, for each sample, with the increase in the copolymer:siRNA weight ratio (R). On the other hand, the susceptibility of loaded siRNA towards RNase decreases with the increase in the pegylated component in the polymeric mixture. At all R values, the average size and the zeta potential values are suitable for escaping from the RES system and suitable for prolonged intravenous circulation. By means of biological characterisation, it was shown that MCF-7 cells are able to internalize mainly the siRNA-loaded into EGF-decorated complexes, with a significant difference from ICONs, confirming its targeting function. The targeting effect of EGF on EP-ICONs was further demonstrated by a competitive cell uptake study, i.e., after cell pre-treatment with EGF. Finally, it was shown that the complexes containing both EGF and PEG are capable of promoting the internalisation and therefore the transfection of siSUR, a siRNA acting against surviving mRNA, and to increase the sensitivity to an anticancer agent, such as doxorubicin.

Author(s):  
P Han ◽  
A Turpie ◽  
E Genton ◽  
M Gent

Platelets play a role in the development and complications of coronary artery disease (CAD) and a number of abnormalities of platelet function which can be corrected by antiplatelet drugs have been described. Betathromboglobulin (BTG), a platelet-specific protein which is released from α-granules during platelet activation is significantly elevated in patients with angiographically demonstrated CAD (51.0 ± 31.0 ng/ml., n = 50) compared to normal (28.0 ± 8.0 ng/ml., n = 70) p < 0.001. The effect of sulphinpyrazone (800 mg.) or aspirin (1200 mg.)/dipyridamole (200 mg.) on plasma BTG in CAD was studied in a blind prospective crossover trial in 25 patients. Mean BTG concentration pre-treatment was 52.3 ng/ml. and after 1 month’s treatment with placebo, sulphinpyrazone or aspirin/dipyridamole mean plasma BTG concentrations were 53.5, 49.6 and 56.7 ng/ml. respectively. Analysis of variance showed no significant difference between the means (p > 0.1) . This study confirms increased plasma BTG concentrations in patients with CAD and indicates that therapeutic doses of these antiplatelet drugs do not significantly effect the BTG level and thus appear not to prevent α-granule release in CAD.


1960 ◽  
Vol XXXV (III) ◽  
pp. 381-396 ◽  
Author(s):  
Sven Almqvist

ABSTRACT The sulfation factor (SF) activity of human sera has been estimated using a modification of the method of Daughaday et al. (1959). Each assay was statistically evaluated. The method had a mean precision of 0.14 and, used as an assay of GH of human serum, a sensitivity in three pituitary dwarfs of 0.1 to 0.6 μg of HGH/ml of serum. SF activity was found at all ages between 1 month and 75 years. There was a significantly lower mean SF activity below the age of half a year. Three cases of pituitary dwarfism had significantly low SF activities of sera. There was no significant difference between the SF activities of sera from untreated pituitary dwarfs and the sera from normal children below half a year of age. Dose-response curves with large volumes of sera from pituitary dwarfs and small volumes of sera from normal humans had the same slopes. Four mg of HGH prepared according to the method of Li & Papkoff (1956) resulted in a normal serum SF activity in each of the three dwarfs. A significant (P < 0.01) linear relationship was found between the concentration of SF activity of sera from these subjects and the logarithm of the dose of HGH given with dose levels of 1, 2 and 4 mg daily for three days. The decline of serum SF activity to the pre-treatment level following HGH in one dwarf suggested a half life not different from that indicated by others for growth hormone.


2017 ◽  
Vol 17 (1) ◽  
pp. 93-98
Author(s):  
Zheng Yue ◽  
Zhang Wen-Cheng ◽  
Wu Ze-Yu ◽  
Fu Chuan-Xiang ◽  
Gao Han ◽  
...  

The purpose of this study was to evaluate the anti-fatigue activity of maca hydroalcoholic extract (ME), which mainly contains macamides and polysaccharides. ME was prepared by circumfluence extraction with enzymatic pre-treatment. Anti-fatigue activity of ME was investigated in weight-loaded forced swimming mice, with pure macamides and commercially available maca tablet as positive control. Compared with normal group, pure macamides treatment group could prolong the swimming time to exhaustion, but there was no statistically significant difference (P > 0.05); while ME (middle-dose and high-dose groups) could effectively prolong the swimming durations (P < 0.05). Supplementation with pure macamides significantly decreased blood lactic acid (BLA), whereas ME significantly increased hepatic glycogen (HG), decreased BLA, and blood urea nitrogen (BUN) compared with those in normal control (P < 0.05). The results suggested that the anti-fatigue effect of ME was better than that of pure macamides, which can be explained by the increase of glycogen storage and the reduction of metabolites accumulation.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Annarita Perillo ◽  
Valeria Landoni ◽  
Alessia Farneti ◽  
Giuseppe Sanguineti

Abstract Purpose The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer. Methods and materials Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated. Results For the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively). Conclusions In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Nattaphop Noothuan ◽  
Kantamas Apitanyasai ◽  
Somsak Panha ◽  
Anchalee Tassanakajon

Abstract Objective Snails secrete different types of mucus that serve several functions, and are increasingly being exploited for medical and cosmetic applications. In this study, we explored the protein pattern and compared the biological properties of the mucus secreted from the mantle collar and foot of two snail species, Lissachatina fulica and Hemiplecta distincta. Result Protein profile showed a different pattern between the two species and between the two secretory parts. The mantle-specific protein bands were further characterized and among them was an antibacterial protein, achacin. Accordingly, the mucus from the mantle exhibited the higher antibacterial activity than that from the foot in both snail species. The mucus from H. distincta, first reported here, also showed antibacterial properties, but with a lower activity compared to that for L. fulica. Snail mucus also exhibited anti-tyrosinase activity and antioxidant activity but with no significant difference between the foot and mantle mucus. These results indicate some different protein compositions and biological activities of snail slime from the mantle and foot, which might be associated with their specific functions in the animal and are useful for medical applications.


1986 ◽  
Vol 71 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Stanley Braude ◽  
David Royston

1. The effect in the rat of salbutamol infusion (1 μg min−1 kg−1) on acid-induced lung injury has been determined. Severity of lung injury was assessed by two techniques: the pulmonary clearance of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and the lung wet/dry weight ratio, giving indices of alveolar epithelial permeability and transendothelial water filtration respectively. 2. Mean half-time of clearance of 99mTc-DTPA was increased significantly in rats who had intratracheal acid-induced injury and control (saline) intravenous infusion (19.4 ± 2.6 min) compared with non-acid-treated rats (98.1 ± 7.2) (P < 0.0001). However, those animals who had intratracheal acid injury and subsequent salbutamol intravenous infusion had significantly faster clearance (11.5 ± 1.9) than the acid and control infusion group (P < 0.05). 3. Gravimetric lung water in the acid-only rats (expressed as wet/dry weight ratio) was increased significantly (6.4 ± 0.3) compared with the non-acid-treated controls (5.4 ± 0.2) (P < 0.01). Acid-treated rats who had salbutamol infused had dramatically increased lung water (10.0 ± 0.6) (P < 0.001 vs acid and control infusion). 4. Intravenous salbutamol infusion itself produced no significant difference in the results for both techniques, compared with the non-acid-treated time-course controls. 5. Infused salbutamol accentuates acid-induced lung injury in the rat. Possible factors responsible for these findings include β2-adrenergic agonist mediated inhibition of hypoxic pulmonary vasoconstriction (HPV) and a predominant β1-adrenergic agonist inotropic effect of salbutamol with resultant rise in pulmonary artery pressure.


Polymers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 831
Author(s):  
Andrea Dodero ◽  
Sonia Scarfi ◽  
Serena Mirata ◽  
Alina Sionkowska ◽  
Silvia Vicini ◽  
...  

Chitosan nanofibrous membranes are prepared via an electrospinning technique and explored as potential wound healing patches. In particular, the effect of a physical or chemical crosslinking treatment on the mat morphological, mechanical, water-related, and biological properties is deeply evaluated. The use of phosphate ions (i.e., physical crosslinking) allows us to obtain smooth and highly homogenous nanofibers with an average size of 190 nm, whereas the use of ethylene glycol diglycidyl ether (i.e., chemical crosslinking) leads to rougher, partially coalesced, and bigger nanofibers with an average dimension of 270 nm. Additionally, the physically crosslinked mats show enhanced mechanical performances, as well as greater water vapour permeability and hydrophilicity, with respect to the chemically crosslinked ones. Above all, cell adhesion and cytotoxicity experiments demonstrate that the use of phosphate ions as crosslinkers significantly improves the capability of chitosan mats to promote cell viability owing to their higher biocompatibility. Moreover, tuneable drug delivery properties are achieved for the physically crosslinked mats by a simple post-processing impregnation methodology, thereby indicating the possibility to enrich the prepared membranes with unique features. The results prove that the proposed approach may lead to the preparation of cheap, biocompatible, and efficient chitosan-based nanofibers for biomedical and pharmaceutical applications.


2009 ◽  
Vol 24 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Honório Sampaio Menezes ◽  
Cláudio Galeano Zettler ◽  
Alice Calone ◽  
Jackson Borges Corrêa ◽  
Carla Bartuscheck ◽  
...  

PURPOSE: To compare body weight and length, heart weight and length, heart-to-body weight ratio, glycemia, and morphometric cellular data of offspring of diabetic rats (ODR) and of normal rats (control). METHODS: Diabetes was induced in 3 pregnant Wistar rats, bearing 30 rats, on the 11th day after conception by intraperitoneal injection of 50 mg/kg of streptozotocin. Six normal pregnant Wistar rats, bearing 50 rats, made up the control group. Morphometric data were obtained using a scale for the weight, length, heart and body measurements. Morphometric cellular data were obtained by a computer assisted method applied to the measurements of myocytes. Statistical analysis utilized Student's t-test, ANOVA and Levene test. RESULTS: Control offspring had greater mean body weight and length than offspring of diabetic rats (p < 0.001). Heart weight and length and heart-to-body ratios of newborn rats differed between groups at birth (p < 0.001), but showed no difference at 21 days. Mean nuclei area and perimetric value of the myocytes decrees throughout the first 21 days of life (p < 0.01) in the diabetic group. CONCLUSIONS: Heart hypertrophy on the offspring of diabetic rats at birth was demonstrated by the significant difference between the groups. After the eleventh day, no difference was found, which confirmed regression of cardiomegaly. The significant difference between the first and the 21th day of life, for nuclei area feature, demonstrate regression of cardiac hypertrophy in the offspring of diabetic rats.


2016 ◽  
Vol 36 (9) ◽  
pp. 901-909 ◽  
Author(s):  
D Sheela ◽  
R Vijayaraghavan ◽  
S Senthilkumar

Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.


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