scholarly journals Evaluation of the Antitumor Activity by Ni Nanoparticles with Verbascoside

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Mingyue Chen ◽  
Yaqin Zhang ◽  
Bin Huang ◽  
Xueming Yang ◽  
Yunong Wu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
K562 Cells ◽  
Pharmacological Properties ◽  
Ni Nanoparticles ◽  
Transmission Electron

Verbascoside (VB) has attracted a great deal of attention due to ITS pharmacological properties. In our study, we synthesized a multifunctional verbascoside coated Ni nanoparticles (VB-Ni). Transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) display the characteristics of VB-Ni nanoparticles. Compared with VB, VB-Ni has been proven to induce apoptosis and resist the growth of doxorubicin-resistant K562 cellsin vitroandin vivo. Thus, VB-Ni nanoparticles can be thought of as an ideal mode of cancer treatment.

scholarly journals Human Islet Amyloid Polypeptide Fibril Binding to Catalase: A Transmission Electron Microscopy and Microplate Study

2010 ◽  
Vol 10 ◽  
pp. 879-893 ◽  
Author(s):  
Nathaniel G. N. Milton ◽  
J. Robin Harris
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Islet Amyloid Polypeptide ◽  
Amyloid Β ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Transmission Electron

The diabetes-associated human islet amyloid polypeptide (IAPP) is a 37-amino-acid peptide that forms fibrilsin vitroandin vivo. Human IAPP fibrils are toxic in a similar manner to Alzheimer's amyloid-β (Aβ) and prion protein (PrP) fibrils. Previous studies have shown that catalase binds to Aβ fibrils and appears to recognize a region containing the Gly-Ala-Ile-Ile sequence that is similar to the Gly-Ala-Ile-Leu sequence found in human IAPP residues 24-27. This study presents a transmission electron microscopy (TEM)—based analysis of fibril formation and the binding of human erythrocyte catalase to IAPP fibrils. The results show that human IAPP 1-37, 8-37, and 20-29 peptides form fibrils with diverse and polymorphic structures. All three forms of IAPP bound catalase, and complexes of IAPP 1-37 or 8-37 with catalase were identified by immunoassay. The binding of biotinylated IAPP to catalase was high affinity with a KDof 0.77nM, and could be inhibited by either human or rat IAPP 1-37 and 8-37 forms. Fibrils formed by the PrP 118-135 peptide with a Gly-Ala-Val-Val sequence also bound catalase. These results suggest that catalase recognizes a Gly-Ala-Ile-Leu—like sequence in amyloid fibril-forming peptides. For IAPP 1-37 and 8-37, the catalase binding was primarily directed towards fibrillar rather than ribbon-like structures, suggesting differences in the accessibility of the human IAPP 24-27 Gly-Ala-Ile-Leu region. This suggests that catalase may be able to discriminate between different structural forms of IAPP fibrils. The ability of catalase to bind IAPP, Aβ, and PrP fibrils demonstrates the presence of similar accessible structural motifs that may be targets for antiamyloid therapeutic development.

scholarly journals Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 263 ◽  
Author(s):  
Maria Letizia Manca ◽  
Iris Usach ◽  
José Esteban Peris ◽  
Antonella Ibba ◽  
Germano Orrù ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Chemical Properties ◽  
Chemical Characterization ◽  
Yeast Cells ◽  
Unilamellar Vesicles ◽  
Transmission Electron ◽  
Physico Chemical

New three-dimensionally-structured hybrid phospholipid vesicles, able to load clotrimazole in a high amount (10 mg/mL), were obtained for the first time in this work by significantly reducing the amount of water (≤10%), which was replaced with a mixture of glycerol and ethanol (≈90%). A pre-formulation study was carried out to evaluate the effect of both the composition of the hydrating medium and the concentration of the phospholipid on the physico-chemical properties of hybrid vesicles. Four different three-dimensionally-structured hybrid vesicles were selected as ideal systems for the topical application of clotrimazole. An extensive physico-chemical characterization performed using transmission electron microscopy (TEM), cryogenic transmission electron microscopy (cryo-TEM), 31P-NMR, and small-angle X-ray scattering (SAXS) displayed the formation of small, multi-, and unilamellar vesicles very close to each other, and was capable of forming a three-dimensional network, which stabilized the dispersion. Additionally, the dilution of the dispersion with water reduced the interactions between vesicles, leading to the formation of single unilamellar vesicles. The evaluation of the in vitro percutaneous delivery of clotrimazole showed an improved drug deposition in the skin strata provided by the three-dimensionally-structured vesicles with respect to the commercial cream (Canesten®) used as a reference. Hybrid vesicles were highly biocompatible and showed a significant antifungal activity in vitro, greater than the commercial cream Canesten®. The antimycotic efficacy of formulations was confirmed by the reduced proliferation of the yeast cells at the site of infection in vivo. In light of these results, clotrimazole-loaded, three-dimensionally-structured hybrid vesicles appear to be one of the most innovative and promising formulations for the treatment of candidiasis infections.

Yolk platelet degradation in preemergence Artemia embryos: response to protons in vivo and in vitro

1987 ◽  
Vol 252 (4) ◽  
pp. R774-R781 ◽  
Author(s):  
P. J. Utterback ◽  
S. C. Hand
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Dry Weight ◽  
Platelet Protein ◽  
Transmission Electron ◽  
Structural Differences ◽  
Alkaline Conditions ◽  
Yolk Platelet

Alteration of intracellular pH (pHi) influences yolk platelet degradation during preemergence development in Artemia embryos. Cysts incubated for 10 h under conditions of aerobic development (aqueous medium equilibrated with 60% N2-40% O2, pHi greater than or equal to 7.9) exhibit a significant decrease in numbers of yolk platelets and platelet protein. In contrast, cysts incubated for 10 h under aerobic acidosis (60% CO2-40% O2, pHi = 6.8) show no significant decrease in numbers of yolk platelets or platelet protein. When subjected to alkaline conditions in vitro, yolk platelets release protein exponentially as a function of time. The process is essentially complete in 40 min. The extent of protein and lipid release from platelets increases markedly as pH of the medium is raised in increments from 6.3 to 8.0. Concomitant with these changes are reduction (50%) in platelet dry weight and reduction (21%) in platelet diameter. Transmission electron microscopy does not reveal major structural differences between isolated yolk platelets and those contained in hydrated embryos. The proton effects on platelet composition and size detected in vitro may explain in part the mechanism of platelet degradation observed during aerobic development and its suppression under conditions of acidic pHi.

Morphometrical Ultrastructural Studies of the Rat's Hepatocytes Under Cooling

1997 ◽  
Vol 3 (S2) ◽  
pp. 245-246
Author(s):  
A.S. Kaprelyants ◽  
A.A. Kaprelyants ◽  
A.N. Reylan ◽  
R.K. Migunova
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Electron Microscopic ◽  
Rat Hepatocyte ◽  
Ultrastructural Studies ◽  
Transmission Electron ◽  
Transmission Electron Microscopic ◽  
Morphometric Methods

The aim of given investigation is to study the effect of cooling upon rat hepatocyte structure using transmission electron microscopic and computer morphometric methods. Ultrastructural and morphometrical characteristics of hepatocytes under liver cooling for various levels under in vivo and in vitro conditions were investigated. Vistar rats of 180-250 g were used in the experiment. Liver cooling (in vivo) was performed by means of original cryoapplicator with different probe temperature (1,2). Liver tissue for transmission electron microscopy was fixed in glutaraldehyde fixator on cocadylate buffer and OsO4. Dehydration was completed on acetone (3). Tissue embedding was done into the mixture of Epon/Araldite epoxy rasin. Ultrathin slices were contrasted by the method of Reinolds. Cell viewing and imaging were accomplished by electron microscope at accelerating power of 75kV.Morphometrical and stereometrical analysis was performed using the “Morpho-Tools” original computer system (c) 1994-1996 A.S. Kaprelyants, A.A. Kaprelyants, A.N. Reylan .

scholarly journals Behavior of plasminogen at the luminal surface of the normal and deendothelialized rabbit aorta in vivo and in vitro

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1260-1267 ◽  
Author(s):  
MW Hatton ◽  
SL Moar ◽  
M Richardson
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Luminal Surface ◽  
Plasmin Activity ◽  
Transmission Electron ◽  
Rapid Adsorption

Abstract The behavior of purified rabbit plasminogen at the luminal surface of the uninjured and deendothelialized rabbit aorta has been studied in vivo and in vitro. After intravenous injection, 125I-plasminogen associated rapidly with the endothelium (approximately 0.1 pmol/cm2 at saturation) and passed through to accumulate in the subendothelium. At two to 15 hours after injection, 11 to 15 times more radioactivity was associated with the subendothelium than with the endothelium. Removal of the endothelium by balloon catheter led to a rapid adsorption of 125I-plasminogen by the luminal surface of the vessel; saturation (9.1 pmol/cm2) was attained at ten to 20 minutes after deendothelialization. Of the adsorbed plasminogen (radioactivity), only 2% to 4% was associated with the adherent platelet monolayer. Uptake of 125I- plasminogen by the deendothelialized vessel was not significantly inhibited by epsilon-aminohexanoic acid whether injected before or after the 125I-plasminogen. No evidence of plasmin activity at the aorta surface was found from either transmission electron microscopy studies or from amidolytic assays of plasminogen-saturated deendothelialized aorta samples before or after urokinase treatment. Balloon catheter treatment in vivo, however, generated significant antiplasmin activity of the deendothelialized aorta surface. We conclude that plasmin formed in vivo is probably inactivated by the antiplasmin activity that is associated with the subendothelium.

Filaments of surfactant protein A specifically interact with corrugated surfaces of phospholipid membranes

1999 ◽  
Vol 276 (4) ◽  
pp. L631-L641 ◽  
Author(s):  
Nades Palaniyar ◽  
Ross A. Ridsdale ◽  
Stephen A. Hearn ◽  
Yew Meng Heng ◽  
F. Peter Ottensmeyer ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Protein A ◽  
Lipid Vesicles ◽  
Surfactant Protein ◽  
Uranyl Acetate ◽  
Lipid Vesicle ◽  
Transmission Electron

Pulmonary surfactant, a mixture of lipids and surfactant proteins (SPs), plays an important role in respiration and gas exchange. SP-A, the major SP, exists as an octadecamer that can self-associate to form elongated protein filaments in vitro. We have studied here the association of purified bovine SP-A with lipid vesicle bilayers in vitro with negative staining with uranyl acetate and transmission electron microscopy. Native bovine surfactant was also examined by transmission electron microscopy of thinly sectioned embedded material. Lipid vesicles made from dipalmitoylphosphatidylcholine and egg phosphatidylcholine (1:1 wt/wt) generally showed a smooth surface morphology, but some large vesicles showed a corrugated one. On the smooth-surfaced vesicles, SP-As primarily interacted in the form of separate octadecamers or as multidirectional protein networks. On the surfaces of the striated vesicles, SP-As primarily formed regularly spaced unidirectional filaments. The mean spacing between adjacent striations and between adjacent filaments was 49 nm. The striated surfaces were not essential for the formation of filaments but appeared to stabilize them. In native surfactant preparations, SP-A was detected in the dense layers. This latter arrangement of the lipid bilayer-associated SP-As supported the potential relevance of the in vitro structures to the in vivo situation.

scholarly journals Topical Delivery of Apremilast Loaded Nanostructured Lipid Carrier Based Hydrogel for Psoriasis Therapy

2021 ◽  
pp. 7-20
Author(s):  
S. M. Sindhoor ◽  
Marina Koland
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Extended Release ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Transmission Electron ◽  
Psoriasis Therapy ◽  
Systemic Side Effects

Background: Apremilast (APR) is an orally administered selective phosphodiesterase 4 inhibitor approved to treat plaque psoriasis and psoriatic arthritis and is available as an oral tablet formulation. However, its systemic side effects limit its application. The low solubility and permeability of apremilast make it difficult to administer it through the skin. Hence an attempt is made to incorporate apremilast into a suitable nanocarrier to facilitate its topical delivery. Aims: To formulate and characterize Apremilast loaded nanostructured lipid carriers for the management of psoriasis to reduce the systemic side effects. Methodology: Apremilast loaded Nanostructured Lipid carriers (NLC) were prepared by melt emulsification accompanied by probe sonication. The formulation was prepared using GMS, Sefsol 218, Tween 80 and Transcutol P as Solid Lipid, Liquid lipid, Surfactant and Penetration Enhancer. The NLC was incorporated into carbapol 934 dispersion to convert it into a gel. The NLC formulation was evaluated for size, Polydispersity Index, Zeta Potential, Entrapment efficiency,  Transmission Electron Microscopy. After that, the NLC gel was examined for Spreadability, Extrudabilty, Viscosity, In vitro drug release, Ex vivo permeation, Skin deposition and In vivo studies. Results: The formulated Apremilast loaded showed particle size of less than 200 nm (i.e.170.32nm) with a narrow PDI of 0.267. Entrapment efficiency revealed that 89.26±01.22% of the drug was entrapped. Transmission electron microscopy images confirmed the spherical nature of the nanocarrier. The extended-release pattern of the formulated NLC for 24h was observed in the in vitro release studies and followed the Higuchi model(R2=0.9966). Ex vivo permeability showed a 6.14 fold increase in permeability and 74.05±0.25% deposition of apremilast loaded NLC gel compared to apremilast gel. The formulation was stable for three months without significant changes. In vivo skin studies showed that the prepared NLC did not have any skin irritation potential. The antipsoriatic activity demonstrated by the Apremilast loaded NLC gel in the imiquimod induced psoriasis model in mice was comparable to the standard treatment. Conclusion: Apremilast loaded NLC demonstrated enhanced permeation, improved skin retention and extended-release compared to conventional gel. The developed formulation can be an alternative for psoriasis therapy after clinical trials in the future.

Design, technological development and evaluation of stimuli-responsive chimeric nanocarriers for cancer therapy

2019 ◽  
Author(s):  
Νικόλαος Ναζίρης
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Differential Scanning Calorimetry ◽  
Technological Development ◽  
Stimuli Responsive ◽  
Scanning Calorimetry ◽  
Transmission Electron ◽  
Micro Dsc

Η επιστήμη έχει σημαντικά επιτεύγματα μέσω της Νανοτεχνολογίας, με εφαρμογές οι οποίες ξεπερνούν κατά πολύ τις δυνατότητες των συμβατικών μέσων σε πολλά επιστημονικά πεδία, συμπεριλαμβανομένης της Ιατρικής και της Φαρμακευτικής. Η Νανοϊατρική ευδοκιμεί μετά την ανάπτυξη των πρώτων νανοτεχνολογικών φαρμάκων στα τέλη του 20ου αιώνα και αναπτύχθηκε ώστε να αποτελεί μία από τις πιο υποσχόμενες προσπάθειες στον αγώνα κατά των ανθρωπίνων ασθενειών. Σε αυτό το πλαίσιο, τα λιποσώματα από καιρού αξιοποιούνται ως νανοτεχνολογικοί φορείς φαρμακομορίων και θεωρούνται ως μία από τις πιο καλώς μελετημένες πλατφόρμες για αυτόν τον σκοπό. Αυτοί οι νανοφορείς ομοιάζουν με τα κύτταρα και χαρακτηρίζονται από δομή και ιδιότητες στη μεσοκλίμακα τα οποία είναι δυναμικά, κυριαρχούμενα από το μηχανισμό και τους νόμους που διέπουν την αυτο-συναρμολόγηση. Η διαδικασία αυτή φέρει κρίσιμη σημασία για την ανάπτυξη νέων και καινοτόμων φαρμακευτικών προϊόντων, όπως και για τη νομοθετική ρύθμιση των ακολούθων “νανο-ομοειδών” φαρμάκων.Η παρούσα διδακτορική διατριβή πραγματεύεται το σύγχρονο θέμα των αποκρινόμενων σε ερεθίσματα χιμαιρικών/μικτών νανοφορέων για τη θεραπεία του καρκίνου, οι οποίοι ανήκουν στην τάξη των καινοτόμων νανοσυστημάτων μεταφοράς φαρμακομορίων για πολύπλοκες ασθένειες. Σκοπός της έρευνας ήταν ο ορθολογικός σχεδιασμός και η ανάπτυξη χιμαιρικών νανοσυστημάτων, οι οποίοι θα αποκρίνονται σε συγκεκριμένες φυσικές και φυσιολογικές συνθήκες, όπως αλλαγές στη θερμοκρασία και μεταβολές του pH, αλλά και η αξιολόγηση της συμπεριφοράς τους κατά την αυτο-συναρμολόγηση, των τελικών ιδιοτήτων τους και της in vitro και in vivo δράσης τους. Αυτά τα νανοσυστήματα αποτελούνται από δύο διαφορετικές τάξεις βιοϋλικών, ήτοι φωσφολιπίδια και αμφίφιλα δισυσταδικά συμπολυμερή και είναι υποσχόμενοι φαρμακοφορείς για τη θεραπεία διαφόρων τύπων καρκίνου, μεταφέροντας και απελευθερώνοντας θεραπευτικούς παράγοντες επιλεκτικά στο σημείο της νόσου.Τα αναλυτικά εργαλεία τα οποία χρησιμοποιήθηκαν για την αξιολόγηση των αλληλεπιδράσεων μεταξύ των βιοϋλικών και της αυτο-συναρμολογήσεώς τους συνεισφέρουν στην ανάπτυξη ποιοτικών νανοτεχνολογικών σκευασμάτων, προσφέροντας γνώση επί των ιδιοτήτων στη νανοκλίμακα αυτών των συστημάτων και της σχέσεις τους με τον τελικό νανοφορέα. Τα εργαλεία αυτά σχετίζονται με τη θερμοδυναμική, τις φυσικοχημικές ιδιότητες, τη σταθερότητα, τη μορφολογία, τη βιοφυσική και τη λειτουργικότητα και τελικώς, με τη βιολογική τοξικότητα και αποτελεσματικότητα των χιμαιρικών νανοσυστημάτων. Συγκεκριμένα, αυτά περιλαμβάνουν τη θερμική ανάλυση, όπως είναι η διαφορική θερμιδομετρία σαρώσεως (differential scanning calorimetry, DSC) ή η micro-DSC, τη σκέδαση φωτός, τεχνικές απεικονίσεως, όπως είναι η ηλεκτρονική μικροσκοπία διαπερατότητας (transmission electron microscopy, TEM) και η κρυογονική ηλεκτρονική μικροσκοπία μεταδόσεως διαπερατότητας (cryogenic TEM, cryo-TEM) και τέλος, βιολογικές δοκιμασίες, μέσω in vitro και in vivo μοντέλων. Ο πλήρης χαρακτηρισμός ενός νανοσυστήματος, όπως τα λιποσώματα, βάσει των εργαλείων αυτών, όχι μόνο συνδράμει στην ανάπτυξη καινοτόμων νανοσυστημάτων μεταφοράς φαρμακομορίων, αλλά και στην κατανόηση του ρόλου του κάθε μοριακού συστατικού του συστήματος και της διαδικασίας της αυτo-οργανώσεως στο τελικό φαρμακευτικό προϊόν.Τελικώς, η παρούσα διδακτορική έρευνα οδήγησε στην ανάπτυξη βιοσυμβατών και λειτουργικών χιμαιρικών νανοσυστημάτων, τα οποία είναι υποσχόμενα ως πλατφόρμες μεταφοράς φαρμακομορίων για καρκίνο, μέσω της αποκρινόμενης σε ερεθίσματα συμπεριφοράς τους. Η αξία της εγκαθιδρύσεως μιας λογικής για την αξιολόγηση των νανοσυστημάτων τέτοιου τύπου μέσω του συνδυασμού συγκεκριμένων και σημαντικών εργαλείων είναι επίσης εμφανής και θα προσφέρει γνώση για την περαιτέρω ανάπτυξη καινοτόμων φαρμάκων. Επιπλέον, θα συνδράμει και στη μελέτη και έγκριση των ακολούθων προϊόντων αυτών, τα οποία είναι γνωστά ως “νανο-ομοειδοί”. Τα εργαλεία αυτά αφορούν την αξιολόγηση του μηχανισμού της αυτο-συναρμολογήσεως και της σχέσης της με τις ιδιότητες, την τοξικότητα και τη λειτουργικότητα των καινοτόμων νανοσυστημάτων μεταφοράς φαρμακομορίων, με τελικό στόχο την ανάπτυξη ποιοτικών, ασφαλών και αποτελεσματικών καινοτόμων φαρμάκων για τη θεραπεία του καρκίνου.

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