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.

scholarly journals Preparation and characterization of baicalein loaded phytosomes: Assessment of in vitro parameters

2020 ◽  
Vol 12 (4) ◽  
pp. 22-29
Author(s):  
KanchanV Zade ◽  
Alok Pal Jain
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Differential Scanning Calorimetry ◽  
Herbal Extracts ◽  
Scanning Calorimetry ◽  
Reverse Phase ◽  
Tem Analysis ◽  
Transmission Electron

Phytosome is a complex between natural active ingredient and a phospholipid. Further, phytosomes been applied to many popular herbal extracts or active molecules for augmenting oral dissolution. Therefore, in present investigation, orally administered Baicalein, atype of flavanoids, is poorly absorbed, and shows suboptimal dissolution. The phytosomes encapsulating baicalein (1:1 Mm) were prepared by reverse phase evaporation method followed by lyophilization. Transmission electron microscopy (TEM) analysis revealed that phytosomes were almost spherical in shape with particle size below 100 nm. The Powder ex-ray diffraction (PXRD) and differential scanning calorimetry (DSC) demonstrated that Baicalein loaded phytosomes were amorphous in nature. Amorphization of therapeutic moiety leads to improvement in dissolution. In conclusion, epigallocatechin loaded phytosomes exhibited promising results and warrant further in vitro andin vivo investigations under a set of stringent parameters for transforming in to a clinically viable products.

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.

Reactions in Metal-Metalloid Multilayers

1993 ◽  
Vol 311 ◽  
Author(s):  
Robert Sinclair ◽  
Toyohiko J. Konno
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Differential Scanning Calorimetry ◽  
Reactive Systems ◽  
Nucleation And Growth ◽  
In Situ Observation ◽  
Scanning Calorimetry ◽  
Compound Formation ◽  
Transmission Electron

ABSTRACTWe have studied the reactions at metal-metalloid interfaces using high resolution transmission electron microscopy, including in situ observation, and differential scanning calorimetry. There is contrasting behavior depending on the affinity for interaction or segregation. For reactive systems, compound formation ultimately results, but this can be preceded by solidstate amorphization. For non-reactive systems, crystallization of the metalloid is often achieved with nucleation and growth mediated by the metal phase.

Crystallization of Amorphous Si In Al/Si Multilayers

1991 ◽  
Vol 230 ◽  
Author(s):  
Toyohiko J. Konno ◽  
Robert Sinclair
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Differential Scanning Calorimetry ◽  
Layered Structure ◽  
Heat Of Reaction ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Transmission Electron ◽  
Amorphous Si

AbstractThe crystallization of amorphous Si in a Al/Si multilayer (with a modulation length of about 120Å) was investigated using transmission electron microscopy, differential scanning calorimetry and X-ray diffraction. Amorphous Si was found to crystallize at about 175 °C with the heat of reaction of 11±2(kJ/mol). Al grains grow prior to the nucleation of crystalline Si. The crystalline Si was found to nucleate within the grown Al layers. The incipient crystalline Si initially grows within the Al layer and then spreads through the amorphous Si and other Al layers. Because of extensive intermixing, the original layered structure is destroyed. The Al(111) texture is also enhanced.

Low-temperature instability of Ti2SnC: A combined transmission electron microscopy, differential scanning calorimetry, and x-ray diffraction investigations

2009 ◽  
Vol 24 (1) ◽  
pp. 39-49 ◽  
Author(s):  
J. Zhang ◽  
B. Liu ◽  
J.Y. Wang ◽  
Y.C. Zhou
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Differential Scanning Calorimetry ◽  
Low Temperature ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Temperature Instability ◽  
X Ray ◽  
Transmission Electron ◽  
Ceramic Microstructure

Transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and x-ray diffraction (XRD) investigations were conducted on the hot-pressed Ti2SnC bulk ceramic. Microstructure features of bulk Ti2SnC ceramic were characterized by using TEM, and a needle-shaped β-Sn precipitation was observed inside Ti2SnC grains with the orientation relationship: (0001) Ti2SnC // (200) Sn and Ti2SnC // [001] Sn. With the combination of DSC and XRD analyses, the precipitation of metallic Sn was demonstrated to be a thermal stress-induced process during the cooling procedure. The reheating temperature, even as low as 400 °C, could trigger the precipitation of Sn from Ti2SnC, which indicated the low-temperature instability of Ti2SnC. A substoichiometry Ti2SnxC formed after depletion of Sn from ternary Ti2SnC phase. Under electron beam irradiation, metallic Sn was observed diffusing back into Ti2SnxC. Furthermore, a new Ti7SnC6 phase with the lattice constants of a = 0.32 and c = 4.1 nm was identified and added in the Ti-Sn-C ternary system.

scholarly journals Combined effect of Sn addition and pre-ageing on natural secondary and artificial ageing of Al–Mg–Si alloys

2022 ◽  
Author(s):  
Xingpu Zhang ◽  
Meng Liu ◽  
Jiangwei Wang ◽  
Jixue Li ◽  
John Banhart
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Differential Scanning Calorimetry ◽  
Electrical Resistivity ◽  
Combined Effect ◽  
Artificial Ageing ◽  
Combined Effects ◽  
Natural Ageing ◽  
Scanning Calorimetry ◽  
Transmission Electron

AbstractBoth Sn addition and pre-ageing are known to be effective in maintaining the artificial ageing potential after natural ageing of Al–Mg–Si alloys. In this study, the combined effects of Sn addition and pre-ageing at 100 °C or 180 °C on natural secondary ageing and subsequent artificial ageing of an alloy AA6014 were investigated using hardness, electrical resistivity, differential scanning calorimetry and transmission electron microscopy characterizations. It is found that pre-ageing can suppress natural secondary ageing and improve the artificial ageing hardening kinetics and response after 1 week of natural secondary ageing in both alloys with and without Sn addition. The effect of pre-ageing at 100 °C is more pronounced in the Sn-free alloy while the combination of pre-ageing at 180 °C and adding Sn shows superiority in suppressing natural secondary ageing and thus avoiding the undesired hardening before artificial ageing. Moreover, when natural ageing steps up to 8 h are applied before pre-ageing at 100 °C, the effect of pre-ageing in Sn-added alloy can be further improved. The influence of Sn on vacancies at different ageing temperatures is discussed to explain the observed phenomena. Graphical abstract

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