scholarly journals Using a Microfluidics System to Reproducibly Synthesize Protein Nanoparticles: Factors Contributing to Size, Homogeneity, and Stability

Processes ◽  
2019 ◽  
Vol 7 (5) ◽  
pp. 290 ◽  
Author(s):  
Courtney van Ballegooie ◽  
Alice Man ◽  
Irene Andreu ◽  
Byron D. Gates ◽  
Donald Yapp

The synthesis of Zein nanoparticles (NPs) using conventional methods, such as emulsion solvent diffusion and emulsion solvent evaporation, is often unreliable in replicating particle size and polydispersity between batch-to-batch syntheses. We have systematically examined the parameters for reproducibly synthesizing Zein NPs using a Y-junction microfluidics chip with staggered herringbone micromixers. Our results indicate that the total flow rate of the fluidics system, relative flow rate of the aqueous and organic phase, concentration of the base material and solvent, and properties of the solvent influence the polydispersity and size of the NPs. Trends such as increasing the total flow rate and relative flow rate lead to a decrease in Zein NP size, while increasing the ethanol and Zein concentration lead to an increase in Zein NP size. The solvent property that was found to impact the size of the Zein NPs formed the most was their hydropathy. Solvents that had a hydropathy index most similar to that of Zein formed the smallest Zein NPs. Synthesis consistency was confirmed within and between sample batches. Stabilizing agents, such as sodium caseinate, Tween 80, and Pluronic F-68, were incorporated using the microfluidics system, necessary for in vitro and in vivo use, into Zein-based NPs.

Author(s):  
Svetlana Rudyk ◽  
Sami Al-Khamisi ◽  
Yahya Al-Wahaibi

AbstractFactors limiting foam injection for EOR application are exceptionally low rock permeability and exceedingly high salinity of the formation water. In this regard, foam formation using internal olefin sulfonate is investigated over a wide salinity range (1, 5, 8, 10, and 12% NaCl) through 10 mD limestone. The relationships between pressure drop (dP), apparent viscosity, liquid flow rate, total flow rate, salinity, foam texture, and length of foam drops at the outlet used as an indicator of viscosity are studied. Foaming is observed up to 12% NaCl, compared to a maximum of 8% NaCl in similar core-flooding experiments with 50 mD limestone and 255 mD sandstone. Thus, the salinity limit of foam formation has increased significantly due to the low permeability, which can be explained by the fact that the narrow porous system acts like a membrane with smaller holes. Compared to the increasing dP reported for highly permeable rocks, dP linearly decreases in almost the entire range of gas fraction (fg) at 1–10% NaCl. As fg increases, dP at higher total flow rate is higher at all salinities, but the magnitude of dP controls the dependence of apparent viscosity on total flow rate. Low dP is measured at 1% and 10% NaCl, and high dP is measured at 5, 8, and 12% NaCl. In the case of low dP, the apparent viscosity is higher at higher total flow rate with increasing gas fraction, but similar at two total flow rates with increasing liquid flow rate. In the case of high dP, the apparent viscosity is higher at lower total flow rate, both with an increase in the gas fraction and with an increase in the liquid flow rate. A linear correlation is found between dP or apparent viscosity and liquid flow rate, which defines it as a governing factor of foam flow and can be considered when modeling foam flow.


Author(s):  
Mohsen Hedaya ◽  
Farzana Bandarkar ◽  
Aly Nada

Introduction: The objectives were to prepare, characterize and in vivo evaluate different ibuprofen (IBU) nanosuspensions prepared by ultra-homogenization, after oral administration to rabbits. Methods: The nanosuspensions produced by ultra-homogenization were tested and compared with a marketed IBU suspension for particle size, in vitro dissolution and in vivo absorption. Five groups of rabbits received orally 25 mg/kg of IBU nanosuspension, nanoparticles, unhomogenized suspension, marketed product and untreated suspension. A sixth group received 5 mg/kg IBU intravenously. Serial blood samples were obtained after IBU administration. Results: The formulated nanosuspensions showed significant decrease in particle size. Polyvinyl Pyrrolidone K30 (PP) was found to improve IBU aqueous solubility much better than the other tested polymers. Addition of Tween 80 (TW), in equal amount as PP (IBU: PP:TW, 1:2:2 w/w) resulted in much smaller particle size and better dissolution rate. The Cmax achieved were 14.8±1.64, 11.1±1.37, 9.01±0.761, 7.03±1.38 and 3.23±1.03 μg/ml and the tmax were 36±8.2, 39±8.2, 100±17.3, 112±15 and 105±17 min for the nanosuspension, nanoparticle, unhomogenized suspension, marketed IBU suspension and untreated IBU suspension in water, respectively. Bioavailability of the different formulations relative to the marketed suspension were the highest for nanosuspension> unhomogenized suspension> nanoparticles> untreated IBU suspension. Conclusion: IBU/PP/TW nanosuspensions showed enhanced in vitro dissolution as well as faster rate and higher extent of absorption as indicated from the higher Cmax, shorter tmax and larger AUC. The in vivo data supported the in vitro results. Nanosuspensions prepared by ultra-high-pressure-homogenization technique can be used as a good formulation strategy to enhance the rate and extent of absorption of poorly soluble drugs.


2002 ◽  
Vol 02 (03n04) ◽  
pp. 297-312
Author(s):  
WEN-JEI YANG ◽  
AMR EID ◽  
R. ECHIGO

An experimental study is performed to extract minute gas bubbles from liquids flowing in a simulated cardiopulmonary bypass system using a Venturi-aspirator unit. In other words, oxygen bubbles in oxygenated blood are simulated by air bubbles in water with AP30 (about same viscosity as whole blood). This study is intended to determine the feasibility of using a Venturi aspirator unit to extract minute gas bubbles from a simulated cardiopulmonary bypass system. Testing of the Venturi-type bubble extraction is carried out using three different test sections. Two Venturis are used, and a straight tube configuration is used as a control. The two Venturis are similar, with the exception that one has a longer inlet cone which causes the entering liquid to accelerate at a slower rate. Results are obtained for effectiveness of the aspirator unit as functions of total flow rate, extraction suction, suction pressure difference, and hydraulic head. It is concluded from the study that:(i) The effectiveness of the Venturis is typically between 90 and 100 percent. It increases with an increase in suction or suction pressure difference but decreases with an increase in total flow rate.(ii) The Venturi is most suitable for extraction of minute gas bubbles, especially for use with AP30 (whole blood), which yields substantially higher effectiveness than water.(iii) It is anticipated that a Venturi-aspirator unit can be superior to other bubble separation device as the cardiopulmonary bypass system for applications in extra corporeal blood oxygenation.


2013 ◽  
Vol 15 (1) ◽  
pp. 150-157 ◽  
Author(s):  
L.F.G Oliveira Junior ◽  
R.B. Santos ◽  
F.O. Reis ◽  
S.T Matsumoto ◽  
W.M.S. Bispo ◽  
...  

Neste trabalho foi avaliado o efeito do óleo essencial do fruto de Schinus terebinthifolius sobre o crescimento micelial do fungo Colletotrichum gloeosporioides in vitro, e no desenvolvimento da antracnose no período de pós-colheita em mamões. As diferentes concentrações de óleo foram diluídas em Tween 80 a 8%. No experimento in vitro foram preparados meios de cultura BDA nas concentrações de 0,05; 0,10; 0,25 e 0,50% do óleo essencial. O controle negativo foi realizado apenas com meio BDA e o controle solvente com meio BDA e Tween 80 a 8%. A inibição do crescimento do fungo foi diretamente proporcional à quantidade do óleo e a maior inibição encontrada foi de 79,07% na concentração de óleo de 0,50%. No experimento in vivo os frutos do mamoeiro foram inoculados com o fungo em quatro tratamentos: com biofilme; com biofilme mais 0,50% do óleo; com fungicida Prochloraz e frutos controle. Embora o tratamento com óleo tenha sido eficiente contra o fungo, não foi indicado comercialmente, pois apresentou valores elevados de perda de massa fresca, de firmeza, e também sintomas de fitotoxidade. O óleo tem propriedade antifúngica contra C. gloeosporioides in vitro e in vivo, contudo, não é recomendado para o mamão em função da fitotoxidez


Author(s):  
Marwa H. Abdallah ◽  
Amr S. Abu Lila ◽  
Md. Khalid Anwer ◽  
El-Sayed Khafagy ◽  
Muqtader Mohammad ◽  
...  

The present work was aimed to develop a transferosomal gel of ibuprofen (IBU) for the amelioration of psoriasis like inflammation. Three formulation of IBU loaded transferosomes (TFs1-TFs3) were prepared using different proportions of lipid (phospholipon 90H) and surfactant (tween 80) and further evaluated for vesicle size, zeta potential (ZP), entrapment efficiency and in vitro drug release. The IBU loaded transferosomes (TFs2) was optimized with vesicle size (217±8.4 nm), PDI (0.102), ZP (-31.5±4.3 mV), entrapment efficiency (88.4±6.9%) and drug loading (44.2±2.9%). Further, the optimized IBU loaded transferosomes (TFs2) was incorporated into 1% carbopol 934 gel base and characterized for homogeneity, extrudability, viscosity and drug content. The in vivo pharmacodynamic study of gel exhibited reduction in psoriasis like inflammation in mice. The ibuprofen loaded transferosomal gel was successfully developed and has shown the potential to be a new therapy against psoriasis like inflammation.


2020 ◽  
pp. 69-73
Author(s):  
Svetlana Mikhailovna Dragunova ◽  
Yevgeniy Vladimirovich, Кuznetsov ◽  
Anna Yevgenievna Khadzhidi

The article solves the problem of increasing the level of protection of juvenile fish to a standard indicator by the modernization of individual elements of fish protection of ameliorative water intake of irrigation systems. The design of an integrated fish-protecting structure with a logging boom adapted to hydrology and the rhythm of migration of juvenile fish from irrigation sources has been proposed. The results of studies on a physical model, taking into account the costs of the reclamation system, show an increase in the efficiency of the combined fish protection structure with a harbor for reclamation water intakes in the range of 78,5–84,0 %, depending on the relative flow rate on the shelf of the sanctuary.


2021 ◽  
Author(s):  
Μαρία Κανναβού
Keyword(s):  
Tween 80 ◽  

Η μεταφορά θεραπευτικών και απεικονιστικών ουσιών στον εγκέφαλο, είναι σε αρκετές περιπτώσεις αδύνατη, λόγω της ύπαρξης του αιματοεγκεφαλικού φραγμού (ΑΕΦ). Η εφαρμογή της νανοτεχνολογίας για την αντιμετώπιση αυτού του προβλήματος έχει αρχίσει προσφάτως να δείχνει σημάδια επιτυχίας. Λόγω της δυσκολίας αντιμετώπισης των νευροεκφυλιστικών νόσων και της επιτακτικής ιατρικής ανάγκης που δεν έχει ως σήμερα αντιμετωπιστεί επιτυχώς, γίνεται μεγάλη προσπάθεια προς αυτή την κατεύθυνση.Πρόσφατα έχει αναδειχτεί η εξαιρετική ικανότητα ορισμένων κυστιδίων που παράγονται από τα κύτταρα (εξωκυτταρικά κυστίδια ή εξωσώματα) να μεταφέρουν επιλεκτικά το φορτίο τους σε άλλα κύτταρα που βρίσκονται πολύ μακριά από τα κύτταρα προέλευσης. Ειδικά τα καρκινικά κύτταρα παράγουν εξωσώματα με πολύ καλό οργανοτροπισμό, ο οποίος έχει αναδειχτεί ότι παίζει σημαντικό ρόλο στη μετάσταση.Στόχος αυτής της διατριβής ήταν η διερεύνηση των μηχανισμών μεταφοράς καθώς και των σημαντικών συστατικών που καθορίζουν την οργανοτροπική δράση κυτταρικών κυστιδίων, ώστε να αποτελέσουν τη βάση για τη μελλοντική ανάπτυξη καινοτόμων μορφών λιποσωμάτων με αυξημένη ικανότητα στόχευσης του εγκεφάλου.Στην παρούσα διατριβή έγινε μελέτη της ικανότητας στόχευσης του εγκεφάλου από κυτταρικά κυστίδια (CVs) που προέρχονται από διαφορετικούς τύπους κυττάρων (φυσιολογικά και καρκινικά) και έχουν διαφορετική ιστική προέλευση, ώστε να εντοπιστούν οι βέλτιστες συστάσεις για στόχευση του εγκεφάλου.Αρχικά, δοκιμάστηκε η απομόνωση κυτταρικών κυστιδίων από φυσιολογικά ανθρώπινα επιθηλιακά κύτταρα εγκεφάλου hCMEC/D3 και από καρκινικά κύτταρα μελανώματος ποντικού B16F10. Τα κυστίδια αυτά χαρακτηρίστηκαν ως προς το μέγεθος, το δείκτη πολυδιασποράς και το ζ-δυναμικό, μελετήθηκε ο ρόλος των κυττάρων προέλευσης των CVs στη δυνατότητά τους να διευκολύνουν τη μεταφορά του περιεχομένου τους σε κύτταρα καθώς και η δυνατότητα τροποποίησής τους για βελτίωση της φαρμακοκινητικής τους. Τα κυστίδια αυτά είναι μη τοξικά και έχουν μέγεθος 100-200nm με αρνητικό επιφανειακό φορτίο. Απ' τα αποτελέσματα είναι εμφανής η αυξημένη αλληλεπίδραση των ομόλογων CVs με τα κύτταρα εγκεφάλου (hCMEC/D3) in vitro αλλά και in vivo επιτυγχάνοντας συσσώρευση μεγαλύτερωνποσότητων στον εγκέφαλο ποντικών. Επιπλέον, μελετήθηκε η επίδραση των μέσων καλλιέργειας στη ικανότητα στόχευσης των CVs και αποδείχτηκε ότι το ειδικό θρεπτικό μέσο για τα hCMEC/D3 (EndoGRO) οδηγεί στη δημιουργία CVs με μεγαλύτερη ικανότητα στόχευσης του εγκεφάλου, σε σύγκριση με CVs μεγαλωμένα στο κοινό θρεπτικό μέσο κυττάρων RPMI. Ο εμπλουτισμός των CVs με χοληστερόλη για αύξηση της ακεραιότητας των κυστιδίων, ήταν δυνατός μόνο σε μεμβράνες με χαμηλή περιεκτικότητα χοληστερόλης (hCMEC/D3 CVs). Η προσθήκη PEG και χοληστερόλης στην επιφάνεια των CVs διευκόλυνε τη μεταφορά των ομόλογων CVs στον εγκέφαλο. Στο πλαίσιο της τροποποίησης των κυτταρικών κυστιδίων, μελετήθηκε και η σύντηξη των CVs με PEG-λιποσώματα. Η τεχνική της σύντηξης δοκιμάστηκε με διαφορετικούς τύπους λιποσωμάτων και κυτταρικών κυστιδίων ώστε να επιβεβαιωθεί η λειτουργικότητά της. Τα υβρίδια μεταξύ PEG-λιποσωμάτων και hCMEC CVs, παρόλο που εμφάνισαν μια ελαφρώς βελτιωμένη φαρμακοκινητική σε σχέση με τα αντίστοιχα CVs, δεν κατάφεραν να επαναλάβουν την ίδια στόχευση εγκεφάλου που πραγματοποιήθηκε από τροποποιημένα Chol/PEG CVs. Στη μελέτη του μηχανισμού δράσης των διάφορων τύπων κυστιδίων που χρησιμοποιήθηκαν σε αυτή τη μελέτη, φαίνεται πως τα CVs και τα υβρίδια αλληλεπιδρούν με τα κύτταρα κυρίως μέσω του μονοπατιού της καβεολίνης, σε αντίθεση με τα τροποποιημένα Chol/PEG CVs που χρησιμοποιούν κυρίως το μονοπάτι της κλαθρίνης.Παράλληλα, μελετήθηκε η ικανότητα εγκλωβισμού καινοτόμων νευροπροστατευτικών και νευροαναγεννητικών συνθετικών μικρονευροτροφινών σε λιποσώματα. Τα μόρια αυτά είναι αρκετά λιπόφιλα και διαπερνούν τον ΑΕΦ. Παρόλα αυτά, η χαμηλή υδατοδιαλυτότητά τους και ο τρόπος χορήγησής τους, περιορίζει τη χρήση τους στη θεραπευτική. Αρχικά, με βάση τα πειράματα προμορφοποίησης προσδιορίστηκαν οι βέλτιστες συστάσεις και μέθοδοι παρασκευής των λιποσωμικών μικρονευροτροφινών (ΒΝΝ27 και ΒΝΝ237). Στη συνέχεια, έγιναν προσπάθειες παρασκευής νανομορφών για ενδορρινική χορήγηση του ΒΝΝ27, με σκοπό την άμεση χορήγησή του στον εγκέφαλο και την αντιμετώπιση των μειονεκτημάτων που εμφανίζονται απ’ τη στόχευση του εγκεφάλου μέσω της ενδοφλέβιας οδού χορήγησης. Μελετήθηκε η επικάλυψη των λιποσωμάτων με χιτοζάνη, ένα παράγοντα με βλεννοσυγκολλητικές ιδιότητες, και προσδιορίστηκε η βέλτιστη σύσταση BNN27 λιποσωμάτων PC/PG (9/1) επικαλυμμένα με 0,1 w/w χιτοζάνη/ λιπίδιο, χρησιμοποιώντας τη χιτοζάνη μεσαίου μοριακού βάρους ως πολυμερές βλεννοπροσκόλλησης. Ακόμα, αναπτύχθηκαν νανογαλακτώματα ΒΝΝ27 με βλεννοσυγκολλητικούς παράγοντες (χιτοζάνη ή Carbopol), ως εναλλακτικοί φορείς ενδορρινικής χορήγησης ΒΝΝ27. Μετά τις κατάλληλες μελέτες προμορφοποίησης, προσδιορίστηκαν οι βέλτιστες συστάσεις ΒΝΝ27 νανογαλακτώματος. Τα νανογαλακτώματα με 8% ή 10% w/w Capmul MCM και χιτοζάνη σε ποσοστό 0,3% w/w εμφάνισαν τα βέλτιστα χαρακτηριστικά σταθερότητας και βλεννοπροσκόλλησης. Ως μίγμα επιφανειοδραστικών χρησιμοποιήθηκαν τα έκδοχα Tween 80 / Transcutol / Propylene glycol σε αναλογία 4/1/1. Οι νανομορφές αυτές αφού χαρακτηρίστηκαν ως προς το μέγεθος των σταγονιδίων, το δείκτη πολυδιασποράς, το ζ-δυναμικό και τη μορφολογία τους, μελετήθηκαν ως προς τη σταθερότητα των φυσικοχημικών τους ιδιοτήτων, την κυτταροτοξικότητα, την ικανότητα διαπέρασης ενός in vitro μοντέλου ΑΕΦ και την in vivo συμπεριφορά μετά από ενδορρινική χορήγηση.


2016 ◽  
Vol 2016 (CICMT) ◽  
pp. 000096-000102
Author(s):  
Houari Cobas Gomez ◽  
Bianca Oliveira Agio ◽  
Jéssica Gonçalves da Silva ◽  
Natalia Neto Pereira Cerize ◽  
Adriano Marim de Oliveira ◽  
...  

Abstract The present work shows a ceramics microfluidic device for non-miscible fluids microemulsion generation using 3D serpentine micromixers. The technology used for device fabrication was Low Temperature Cofired Ceramics (LTCC) which allows us for complex, high temperature and pressure resistant 3D microfluidic devices. The proposed device aims to obtain microemulsion with controlled drop size, low dispersion index and high production volumes using Top-Down approach. Previous simulation work had showed 3D serpentine as one of the best structures for rapid mixing due the chaotic advection generated on every 90 deg direction change. This effect, when mixing two fluids as oil and water leads to streamlines pinching-off making possible drop generation. We have used this effect on our device. For the experimental section, it was fabricated a 3D serpentine mixer microfluidic device with working region suitable for variable total flow rate. For certain value of total flow rate, the microemulsion showed higher drop diameter and polydispersity values. In this region, no control could be done in order to obtain the same drop value with the same process parameters. Inside the working region drop diameter values repeatability was obtained. In this region our experimental results had showed a relation between drop diameter and total flow rate. As a total flow rate increase the drop diameter decrease due to a stronger chaotic advection effect. In the other hand, the polydispersity index also decreases. Microemulsions with average size lower than few micrometer or submicron were obtained. When compared with other reported devices, our device presented a production volume in the range of tens of ml/s for the same output microemulsion size.


1990 ◽  
Vol 258 (4) ◽  
pp. F998-F1004 ◽  
Author(s):  
H. M. Lafferty ◽  
M. Gunning ◽  
H. R. Brady ◽  
B. M. Brenner ◽  
S. Anderson

Manganese (Mn2+) is a cofactor for guanylate cyclase (GC), which is involved in the generation of guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger for atrial natriuretic peptide (ANP) action. Mn2+ is also, however, a nonselective calcium-channel blocker. We examined the effects of infusion of MnCl2 into normal rats and its interaction in vivo and in vitro with GC and ANP. MnCl2 significantly increased glomerular filtration rate (GFR) and effective renal plasma flow rate (RPF). These effects were caused by selective afferent arteriolar vasodilatation, which allowed the glomerular capillary plasma flow rate and hydraulic pressure to rise, thus elevating single-nephron GFR. Urinary Na+ excretion (UNaV) also increased with MnCl2. The natriuresis was, unlike ANP, not mediated by GC activation and cGMP production, as MnCl2 had no effect on either urinary cGMP excretion or cGMP accumulation in intact inner medullary collecting duct cell (IMCD) suspensions, nor did it affect Na(+)-dependent oxygen consumption in these cells. When superimposed on an infusion of ANP, MnCl2 resulted in significant increases in UNaV, GFR, and RPF. These effects were associated with small but significant increments in urinary cGMP excretion. However, MnCl2 did not affect in vitro cGMP production in intact IMCDs or glomeruli in response to ANP stimulation. It is uncertain therefore whether the in vivo augmentation of the natriuretic effect of ANP by MnCl2 is related to GC activation and cGMP production.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 465 ◽  
Author(s):  
Eman A. Mazyed ◽  
Abdelaziz E. Abdelaziz

Acetazolamide (ACZ) is a potent carbonic anhydrase inhibitor that is used for the treatment of glaucoma. Its oral administration causes various undesirable side effects. This study aimed to formulate transgelosomes (TGS) for enhancing the ocular delivery of ACZ. ACZ-loaded transfersomes were formulated by the ethanol injection method, using phosphatidylcholine (PC) and different edge activators, including Tween 80, Span 60, and Cremophor RH 40. The effects of the ratio of lipid to surfactant and type of surfactant on % drug released after 8 h (Q8h) and entrapment efficiency (EE%) were investigated by using Design-Expert software. The optimized formula was formulated as TGS, using poloxamers as gelling agents. In vitro and in vivo characterization of ACZ-loaded TGS was performed. According to optimization study, F8 had the highest desirability value and was chosen as the optimized formula for preparing TGS. F8 appeared as spherical elastic nanovesicles with Q8h of 93.01 ± 3.76% and EE% of 84.44 ± 2.82. Compared to a free drug, TGS exhibited more prolonged drug release of 71.28 ± 0.46% after 8 h, higher ex vivo permeation of 66.82 ± 1.11% after 8 h and a significant lowering of intraocular pressure (IOP) for 24 h. Therefore, TGS provided a promising technique for improving the corneal delivery of ACZ.


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