scholarly journals Τεχνολογία δευτερογενών μεταβολιτών

2011 ◽  
Author(s):  
Κωνσταντίνος Κοντογιαννόπουλος
Keyword(s):  
Burst Release ◽  
Alkanna Tinctoria ◽  
Egg Pc

Η παρούσα διδακτορική διατριβή μελετά το σχεδιασμό, την ανάπτυξη και τον χαρακτηρισμό καινοτόμων συστημάτων μεταφοράς και αποδέσμευσης για τη βιοδραστική ουσία σικονίνη, αλκαννίνη και τα παράγωγά της, οι οποίες εμφανίζουν ισχυρή επουλωτική, αντιμικροβιακή, αντιφλεγμονώδη και αντικαρκινική δράση. Στόχος ήταν να συνδυαστούν οι βιολογικές ιδιότητες της φυσικών αυτών προϊόντων με τα πλεονεκτήματα που προσφέρουν τα συστήματα μεταφοράς φάρμακου, επιτυγχάνοντας ελεγχόμενη αποδέσμευση στην επιθυμητή περιοχή δράσης. Για το σκοπό αυτό, παρασκευάσθηκαν συμβατικά και σταθεροποιημένα λιποσωμιακά συστήματα, δενδριτικά συστήματα, καθώς και χιμαιρικά λιποσωμιακά συστήματα (συνδυάζοντας την δενδριτική με την λιποσωμιακή τεχνολογία) μεταφοράς και αποδέσμευσης για τη σικονίνη. Τέλος, παρασκευάσθηκαν νανοΐνες ηλεκτροστατικής ινοποίησης από διάφορα βιοαποκοδομήσιμα πολυμερή με δραστική ουσία σικονίνη ή μίγμα αλκαννίνης/σικονίνης και εστέρων τους, που απομονώθηκε από τις ρίζες του φυτού Alkanna tinctoria, ως σκεύασμα εξωτερικής χρήσης με επουλωτική και αντιμικροβιακή δράση. Για την παρασκευή των συμβατικών λιποσωμιακών σκευασμάτων χρησιμοποιήθηκαν δύο τύποι λιπιδίων (Egg-PC και DPPC) και διάφορες αρχικές συγκεντρώσεις σικονίνης. Το μέσο μέγεθος των σωματιδίων κυμαίνεται μεταξύ 120 και 280 nm, ενώ οι τιμές ζ-δυναμικού τους μεταξύ -4 mV έως -17 mV. Τα ποσοστά εγκλεισμού τους βρέθηκαν μεγαλύτερα από 60%, ενώ επιβεβαιώθηκε η επιθυμητή ελεγχόμενη αποδέσμευση της δραστικής ουσίας. Τέλος, τα παρασκευασθέντα δείγματα εμφάνισαν ικανοποιητική in vitro κυτταροτοξική δράση σε δύο καρκινικές σειρές (MCF7-καρκίνος του μαστού και SF268-γλοίωμα). Τα στερεοχημικά σταθεροποιημένα λιποσωμιακά συστήματα σικονίνης παρασκευάσθηκαν με τρεις τύπους λιπιδίων (Egg-PC, DSPC, DPPC) και με σταθεροποιητικό παράγοντα DSPE-mPEG2000. Εμφανίζουν βελτιωμένα φυσικοχημικά χαρακτηριστικά (μικρότερο μέσο μέγεθος, υψηλότερες τιμές ζ-δυναμικού), υψηλότερα ποσοστά εγκλεισμού, καθώς και αυξημένη σταθερότητα σε σύγκριση με τα αντίστοιχα συμβατικά λιποσώματα σικονίνης. Τέλος, χαρακτηρίζονται από παρατεταμένη αποδέσμευση δραστικής ουσίας που φτάνει μέχρι τις 72 ώρες. Τρεις γενιές υπερδιακλαδισμένων πολυμερών (ΥΠ) (PFH-16-OH, PFH-32-OH και PFH-64-OH) χρησιμοποιήθηκαν για την παρασκευή δενδριτικών συστημάτων μεταφοράς και αποδέσμευσης σικονίνης, με το υπερδιακλαδισμένο πολυμερές 4ης γενιάς (PFH–64–OH) να εμφανίζει πάντοτε το υψηλότερο ποσοστό εγκλεισμού. H χρήση μεθανόλης κατά τη διεργασία της συμπλοκοποίησης αυξάνει την αποτελεσματικότητα του εγκλεισμού. Τέλος, τα δείγματα εμφάνισαν μέτρια σταθερότητα κατά την παραμονή τους στους 4°C. Τα χιμαιρικά λιποσωμιακά συστήματα σικονίνης (chi-aDDnSs), παρασκευάσθηκαν με εγκλωβισμό των συμπλόκων σικονίνης/ΥΠ σε λιποσώματα με λιπίδιο Egg-PC. Το μέσο μέγεθός τους βρέθηκε ανάλογο με των αντίστοιχων συμβατικών λιποσωμάτων, ενώ η αποτελεσματικότητα του εγκλεισμού φάνηκε να εξαρτάται από τη μέθοδο παρασκευής που χρησιμοποιήθηκε. Τα χιμαιρικά λιποσωμιακά συστήματα, αύξησαν την σταθερότητα των συμπλόκων σικονίνης/ΥΠ, ενώ χαρακτηρίζονται και από ικανοποιητικό προφίλ αποδέσμευσης. Για την παρασκευή νανοϊνών ηλεκτροϊνοποίησης χρησιμοποιήθηκαν τέσσερα βιοποικοδομήσιμα πολυμερή (CA, PLLA, PLGA 50:50 και PLGA 75:25), καθώς και διαφορετικές αρχικές συγκεντρώσεις σικονίνης και μίγματος εστέρων αλκαννίνης/σικονίνης. Οι παρασκευασθείσες νανοΐνες παρουσιάζουν ιδιαίτερα ικανοποιητική μορφολογία (με μεγέθη στην κλίμακα των νανομέτρων) και υψηλά ποσοστά εγκλεισμού που εξαρτώνται από τον τύπο του χρησιμοποιούμενου πολυμερούς και την αρχική συγκέντρωση φαρμακευτικής ουσίας. Το προφίλ αποδέσμευσης της δραστικής ουσίας είναι ικανοποιητικό, ενώ σε όλες τις περιπτώσεις παρατηρήθηκε έντονη αρχική αποδέσμευσή της (burst release) κατά τα πρώτα 60 λεπτά του πειράματος. Τα συστήματα μεταφοράς και αποδέσμευσης που αναπτύχθηκαν στα πλαίσια της παρούσας διδακτορικής διατριβής εμφανίζουν ιδιαίτερα πλεονεκτήματα και μπορούν να χρησιμοποιηθούν ώστε να αυξηθεί ο θεραπευτικός δείκτης των δραστικών ουσιών που εγκλείστηκαν.

Preparation and In Vitro Evaluation of Resealed Erythrocytes as A New Trend in Treatment of Asthma

2016 ◽  
Vol 6 (3) ◽  
Author(s):  
Mohammed Ibrahim ◽  
Alaa Zaky ◽  
Mohsen Afouna ◽  
Ahmed Samy
Keyword(s):  
In Vitro Release ◽  
Human Erythrocytes ◽  
The Body ◽  
Blood Levels ◽  
Time Interval ◽  
Burst Release ◽  
Prolonged Release ◽  
Nocturnal Asthma ◽  
Carrier Erythrocytes

Carrier erythrocytes are emerging as one of the most promising biological drug delivery systems investigated in recent decades. Beside its biocompatibility, biodegradability and ability to circulate throughout the body, it has the ability to perform extended release system of the drug for a long period. The ultimate goal of this study is to introduce a new carrier system for Salbutamol, maintaining suitable blood levels for a long time, as atrial to resolve the problems of nocturnal asthma medication Therefore in this work we study the effect of time, temperature as well as concentration on the loading of salbutamol in human erythrocytes to be used as systemic sustained release delivery system for this drug. After the loading process is performed the carrier erythrocytes were physically and cellulary characterized. Also, the in vitro release of salbutamol from carrier erythrocytes was studied over time interval. From the results it was found that, human erythrocytes have been successfully loaded with salbutamol using endocytosis method either at 25 Co or at 37 Co . The highest loaded amount was 3.5 mg/ml and 6.5 mg/ml respectively. Moreover, the percent of cells recovery is 90.7± 1.64%. Hematological parameters and osmotic fragility behavior of salbutamol loaded erythrocytes were similar that of native erythrocytes. Scanning electron microscopy demonstrated that the salbutamol loaded cells has moderate change in the morphology. Salbutamol releasing from carrier cell was 43% after 36 hours in phosphate buffer saline. The releasing pattern of the drug from loaded erythrocytes showed initial burst release in the first hour followed by a very slow release, obeying zero order kinetics. It concluded that salbutamol is successfully entrapped into erythrocytes with acceptable loading parameters and moderate morphological changes, this suggesting that erythrocytes can be used as prolonged release carrier for salbutamol.

Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

2018 ◽  
Vol 24 (15) ◽  
pp. 1639-1651 ◽  
Author(s):  
Xian-ling Qian ◽  
Jun Li ◽  
Ran Wei ◽  
Hui Lin ◽  
Li-xia Xiong
Keyword(s):  
Targeted Delivery ◽  
Tumor Therapy ◽  
Burst Release ◽  
Tumor Site ◽  
Chemotherapeutic Drugs ◽  
Triggering Mechanism ◽  
Triggering Factors ◽  
Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

Injectable in-situ Forming Depot Of Doxycycline Hyclate/α-Cyclodextrin Complex using PLGA for Periodontitis Treatment: Preparation, Charac-terization, and In-Vitro Evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Elham Khodaverdi ◽  
Farhad Eisvand ◽  
Mohammad Sina Nezami ◽  
Seyedeh Nesa Rezaeian Shiadeh ◽  
Hossein Kamali ◽  
...  
Keyword(s):  
Complex Form ◽  
Docking Studies ◽  
Morphological Properties ◽  
Burst Release ◽  
Cyclodextrin Complex ◽  
Doxycycline Hyclate ◽  
Scanning Calorimetry ◽  
In Situ Forming

Background:: Doxycycline (DOX) is used in treating a bacterial infection, especially for periodontitis treatment. Objective: To reduce irritation of DOX for subgingival administration and increase the chemical stability and against enzy-matic, the complex of α-cyclodextrin with DOX was prepared and loaded into injectable in situ forming implant based on PLGA. Methods:: FTIR, molecular docking studies, X-ray diffraction, and differential scanning calorimetry was performed to char-acterize the DOX/α-cyclodextrin complex. Finally, the in-vitro drug release and modeling, morphological properties, and cellular cytotoxic effects were also evaluated. Results:: The stability of DOX was improved with complex than pure DOX. The main advantage of the complex is the al-most complete release (96.31 ± 2.56 %) of the drug within 14 days of the implant, whereas in the formulation containing the pure DOX and the physical mixture the DOX with α-cyclodextrin release is reached to 70.18 ± 3.61 % and 77.03 ± 3.56 %, respectively. This trend is due to elevate of DOX stability in the DOX/ α-cyclodextrin complex form within PLGA implant that confirmed by the results of stability. Conclusion:: Our results were indicative that the formulation containing DOX/α-cyclodextrin complex was biocompatible and sustained-release with minimum initial burst release.

scholarly journals Antimicrobial Properties and Release Profile of Ampicillin from Electrospun Poly(εepsilon;-caprolactone) Nanofiber Yarns

2010 ◽  
Vol 5 (4) ◽  
pp. 155892501000500 ◽  
Author(s):  
Hang Liu ◽  
Karen K. Leonas ◽  
Yiping Zhao
Keyword(s):  
In Vitro Release ◽  
Antimicrobial Properties ◽  
Fiber Surface ◽  
Electrospun Nanofibers ◽  
Release Profile ◽  
Burst Release ◽  
Spun Yarns ◽  
Surgical Sutures ◽  
Release Model

Poly(εepsilon;-caprolactone) (PCL) electrospun fibers containing ampicillin sodium salt have been produced and twisted into nanofiber yarns. The fiber diameters and crystallinity, the in vitro antimicrobial properties of the yarns, and the in vitro release of ampicillin from yarns containing various ampicillin concentrations are studied. Decreased fiber diameters and reduced diameter variation are observed with the addition of ampicillin salt into the polymer solution. The results from the zone of inhibition test of the yarns against both gram-positive Staphylococcus aureus and gram-negative Klebsiella pneumoniae indicate that the released ampicillin retains its effectiveness after the production processes, therefore the as-spun yarns are antimicrobial active. A burst release of ampicillin from the yarns has been observed in the first hour, and the release is almost completed in 96 hours. The burst release is believed to be due to the low compatibility of ampicillin with PCL, the accumulation of ampicillin on fiber surface and the small fiber diameters. An empirical release model is developed to describe the release profile. The results indicate that the electrospun nanofibers yarns will have a great potential to be used for biomaterials, such as surgical sutures, to decrease the surgical site infection rate.

scholarly journals Applicability of Gum Karaya in the Preparation and in Vitro Evaluation of Losartan Potassium as Chronotherapeutic Drug Delivery System

2015 ◽  
Vol 7 (1-2) ◽  
pp. 65-74
Author(s):  
K. Latha ◽  
V. V. Srikanth ◽  
S. A. Sunil ◽  
N. R. Srinivasa ◽  
M. U. Uhumwangho ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tensile Strength ◽  
Drug Delivery System ◽  
Delivery System ◽  
Lag Time ◽  
Losartan Potassium ◽  
In Vitro Dissolution ◽  
Burst Release ◽  
Gum Karaya

The objective of this investigation is to study the applicability of gum karaya, the natural gum for the preparation and in vitro evaluation of losartan potassium, as Chronotherapeutic Drug Delivery System (ChDDS). The compression-coated timed-release tablets (CCT) containing losartan potassium in the core tablet were prepared by dry coating technique with different ratios of gum karaya as the outer coat. The parameters investigated were tensile strength, friability, in vitro dissolution studies and drug concentration. The optimized formulation was further characterized by powder XRD and FTIR to investigate interactions and no interactions observed. The tensile strength and friability of all the CCT were between 1.06-1.23 MN/m2 and < 0.3% respectively.  All the CCT showed a clear lag time before a burst release of drug. However, the lag time of drug release increased as the amount of gum karaya in the outer layer increased. For instance, the lag time of LGK1, LGK2, LGK3, LGK4, LGK5, LGK6 and LGK7 were 16, 10.5, 5.5, 3, 2, 1.5 and 0.5 hrs respectively.  The drug content of all the CCT was >98%. Formulation LGK3 was taken as an optimized formulation which can be exploited to achieve ChDDS of losartan potassium for the treatment of hypertension. 

scholarly journals Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery

2021 ◽  
Vol 8 (4) ◽  
pp. 43
Author(s):  
Jihoon Kim ◽  
Jee Seon Kim ◽  
Kyung Hyun Min ◽  
Young-Hwa Kim ◽  
Xiaoyuan Chen
Keyword(s):  
Blood Circulation ◽  
Burst Release ◽  
Oxygen Species ◽  
Antibody Drug Conjugate ◽  
Gastrin Releasing Peptide ◽  
Anticancer Effects ◽  
Efficient Delivery ◽  
Nanoparticle System ◽  
Micelle System

Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody–drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs during blood circulation. Herein, we rationally propose monomethylauristatin F (MMAF), a dolastatin-derived, loaded nanoparticle system composed of bombesin (BBN)-tethered ROS-responsive micelle system (BBN-PEG-PPADT) to achieve efficient anticancer therapy with targeted and efficient delivery of MMAF. The developed MMAF-loaded BBN-PEG-PPADT micelles (MMAF@BBN-PEG-PPADT) exhibited improved cellular uptake via interactions between BBN and gastrin-releasing peptide receptors on the cancer cells and the intracellular burst release of MMAF, owing to the ROS-responsive disruption, which allowed the efficient anticancer effects of MMAF in vitro. This study suggests the potential of nanoparticle systems in the delivery of dolastatin drugs.

scholarly journals Comparison of Chondral Defects Repair with In Vitro and In Vivo Differentiated Mesenchymal Stem Cells

2007 ◽  
Vol 16 (8) ◽  
pp. 823-832 ◽  
Author(s):  
Hongbin Fan ◽  
Haifeng Liu ◽  
Rui Zhu ◽  
Xusheng Li ◽  
Yuming Cui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cartilage Tissue ◽  
Burst Release ◽  
In Vitro Differentiation ◽  
Chondral Defects ◽  
In Vivo Differentiation ◽  
Repair Group

The purpose of this study was to compare chondral defects repair with in vitro and in vivo differentiated mesenchymal stem cells (MSCs). A novel PLGA-gelatin/chondroitin/hyaluronate (PLGA-GCH) hybrid scaffold with transforming growth factor-β1 (TGF-β1)-impregnated microspheres (MS-TGF) was fabricated to mimic the extracellular matrix. MS-TGF showed an initial burst release (22.5%) and a subsequent moderate one that achieved 85.1% on day 21. MSCs seeded on PLGA-GCH/MS-TGF or PLGA-GCH were incubated in vitro and showed that PLGA-GCH/MS-TGF significantly augmented proliferation of MSCs and glycosaminoglycan synthesis compared with PLGA-GCH. Then MSCs seeded on PLGA-GCH/MS-TGF were implanted and differentiated in vivo to repair chondral defect on the right knee of rabbit (in vivo differentiation repair group), while the contralateral defect was repaired with in vitro differentiated MSCs seeded on PLGA-GCH (in vitro differentiation repair group). The histology observation demonstrated that in vivo differentiation repair showed better chondrocyte morphology, integration, and subchondral bone formation compared with in vitro differentiation repair 12 and 24 weeks postoperatively, although there was no significant difference after 6 weeks. The histology grading score comparison also demonstrated the same results. The present study implies that in vivo differentiation induced by PLGA-GCH/MS-TGF and the host microenviroment could keep chondral phenotype and enhance repair. It might serve as another way to induce and expand seed cells in cartilage tissue engineering.

Thermosensitive Hydrogel Incorporating Microspheres for Injectable Implant Delivery of Naltrexone

2013 ◽  
Vol 647 ◽  
pp. 71-79 ◽  
Author(s):  
Guo Qiang Jiang ◽  
Yu Jie Wang ◽  
Fu Xin Ding
Keyword(s):  
Sol Gel ◽  
High Water ◽  
The Body ◽  
High Water Content ◽  
Burst Release ◽  
Thermosensitive Hydrogel ◽  
Sol Gel Transition ◽  
Gel Transition

Long-term drug delivery based on the injectable thermosensitive hydrogel is of great advantage to the administration of naltrexone, but the constant release is hard to reach due to the sol-gel transition and the high water content of the hydrogel. The aim of the present study is to develop an injectable implant delivery system by the incorporation of microspheres into thermosensitive hydrogel for the long-term constant release of naltrexone. Naltrexone was loaded in PLGA microsphere dispersed in the methylcellulose based thermosensitive sol, which formed the hydrogel containing the naltrexone-loaded microspheres at the body temperature. The presence of microsphere in the hydrogel delayed the sol-gel transition slightly but enhanced the mechanical strength of the hydrogel significantly. The microspheres degradation in water diffusion dominated phase was decelerated when they were embed in the hydrogel. The in vitro naltrexone release from the microsphere/hydrogel system showed an over 60 days constant release with no significant burst release, and the drug release rate was in proportion to the microsphere concentration in the hydrogel.

Mixed Poloxamer Nanomicelles for the Anticonvulsant Lamotrigine Drug: Solubility, Micellar Characterization, and In-Vitro Release Studies

2021 ◽  
Vol 21 (11) ◽  
pp. 5723-5735
Author(s):  
Sofiya Shaikh ◽  
Hemil Patel ◽  
Debes Ray ◽  
Vinod K. Aswal ◽  
Rakesh K. Sharma
Keyword(s):  
In Vitro Release ◽  
Systematic Investigation ◽  
Burst Release ◽  
Drug Solubility ◽  
Biphasic Model ◽  
Release Studies ◽  
Stability Data ◽  
A Chain ◽  
Vitro Release

Recently the applications of Poloxamers in drug development is promising as it facilitated the drug molecule for delivering to the correct place, at the correct time and in the correct amount. Poloxamers can form nanomicelles to encapsulate hydrophobic drugs in order to increase solubility, stability and facilitate delivery at target. In this context, the solubilization of anticonvulsant lamotrigine (LMN) drug in a chain of Poloxamers containing different polyethylene oxide and polypropylene oxide noieties were examined. The results showed better solubilization of LMN in Poloxamers contain low CMTs while poor with Poloxamers having high CMTs. Systematic investigation of two mixed Poloxamer nanomicelles (P407:P403 and P407:P105) for LMN bioavailability at body temperature (37 °C) were investigated. The solubility of LMN was enhanced in mixed P407:P403 nanomicelles with the amount of P403 and reduced in mixed P407:P105 nanomicelles with the amount of P105. LMN encapsulated mixed Poloxamer nanomicelles were found spherical in shape with ~25 nm Dh sizes. The In-Vitro release profiles of mixed Poloxamer nanomicelles demonstrated the biphasic model with initial burst release and then slowly release of LMN. Better biocompatibility of LMN in the mixed P407:P403 nanomicelles was confirmed with stability data. The results of this work were proven the mixed P407:P403 nanomicelles as efficient nanocarriers for LMN.

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