scholarly journals Mucoadhesive In Situ Rectal Gel Loaded with Rifampicin: Strategy to Improve Bioavailability and Alleviate Liver Toxicity

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 336
Author(s):  
Fakhria Al-Joufi ◽  
Mohammed Elmowafy ◽  
Nabil K. Alruwaili ◽  
Khalid S. Alharbi ◽  
Khaled Shalaby ◽  
...  
Keyword(s):  
Liver Toxicity ◽  
Gel Strength ◽  
Pluronic F127 ◽  
Oral Drug ◽  
Gelation Temperature ◽  
Mucoadhesive Polymers ◽  
Drug Polymer Interaction ◽  
Polymer Interaction

Although it is a front-line in tuberculosis treatment, rifampicin (RF) exhibits poor oral bioavailability and hepatotoxicity. Rectal mucoadhesive and in situ rectal gels were developed to overcome drug drawbacks. A RF/polyethylene glycol 6000 co-precipitate was first prepared in different ratios. Based on the drug solubility, the selected ratio was investigated for drug/polymer interaction and then incorporated into in situ rectal gels using Pluronic F127 (15%) and Pluronic F68 (10%) as a gel base and mucoadhesive polymers (HPMC, sodium alginate and chitosan). The formulations were assessed for gelation temperature and gel strength. The selected formulation was investigated for in vivo assessments. The results showed that a 1:1 drug/polymer ratio exhibited satisfying solubility with the recorded drug/polymer interaction. Depending on their concentrations, adding mucoadhesive polymers shifted the gelation temperature to lower temperatures and improved the gel strength. The selected formulation (F4) did not exhibit any anal leakage or marked rectal irritation. Using a validated chromatographic analytical method, F4 exhibited higher drug absorption with a 3.38-fold and 1.74-fold higher bioavailability when compared to oral drug suspension and solid suppositories, respectively. Toxicity studies showed unnoticeable hepatic injury in terms of biochemical, histopathological and immunohistochemical examinations. Together, F4 showed a potential of enhanced performance and also offered lower hepatic toxicity, thus offering an encouraging therapeutic alternative.

scholarly journals Ανάπτυξη λιποσωμικών μορφών μη-στεροειδών αντιφλεγμονωδών φαρμάκων (ΜΣΑΦ) για οφθαλμική χορήγηση

2017 ◽  
Author(s):  
Κωνσταντίνος Παχής
Keyword(s):  
Pluronic F127

Τα μη Στεροειδή Αντιφλεγμονώδη Φάρμακα (ΜΣΑΦ) αποτελούν εκλεκτικούς ή μη αναστολείς της κυκλοοξυγενάσης (COX), του ενζύμου εκείνου που εμπλέκεται στο μεταβολισμό του αραχιδονικού οξέος σε προσταγλαδίνες. Συνεπώς, αναστέλλουν την εκδήλωση της φλεγμονής. Στην οφθαλμολογία χορηγούνται κατά κύριο λόγο τοπικά, υπό μορφή σταγόνων, σε φλεγμονώδεις εκδηλώσεις, όπως π.χ. το μετεγχειρητικό οίδημα της ωχράς κηλίδας, με όχι πάντα την επιθυμητή αποτελεσματικότητα.Η ενδοϋαλοειδική χρήση τους δοκιμάζεται τα τελευταία χρόνια για το κυστικό οίδημα της ωχράς κηλίδας ποικίλων αιτιών, όπως το μετεγχειρητικό, το διαβητικό και το ραγοειδιτικό, με ενδιαφέροντα αποτελέσματα. Η ενδοϋαλοειδική (IVT) χορήγηση είναι γνωστό ότι επιτυγχάνει σημαντικά υψηλότερα επίπεδα φαρμάκων στον αμφιβληστροειδή (σε σύγκριση με τοπική ή συστηματική χορήγηση), ενώ ελαχιστοποιεί τις συστημικές ανεπιθύμητες ενέργειες. Το βασικό μειονέκτημα των φαρμάκων αυτών είναι ο μικρός χρόνος ημιζωής τους στην υαλοειδική κοιλότητα, που έχει ως αποτέλεσμα να απαιτούνται συχνές εγχύσεις για την επίτευξη του θεραπευτικού στόχου.Με σκοπό την ανάπτυξη ενός συστήματος για παρατεταμένη αποδέσμευση ΜΣΑΦ στο οπίσθιο τμήμα του οφθαλμού, αναπτύχθηκε ένα in-situ δημιουργούμενο σύστημα συσσωμάτωσης λιποσωμάτων (λιποσωμικό συσσωμάτωμα). Για την αρχική διαπίστωση της δυνατότητας ανάπτυξης του συστήματος χρησιμοποιήθηκαν ως μόρια μοντέλα/πρότυπα φαρμακομορίων, η καλσεΐνη και FITC-Δεξτράνη, εγκλωβισμένα σε λιποσώματα, και έγιναν in vitro και in vivo μελέτες ώστε να επιβεβαιωθεί η λειτουργικότητα του συστήματος. Εν συνεχεία, παρασκευάστηκαν (με διάφορες τεχνικές) λιποσώματα λορνοξικάμης και φλουρμπιπροφαίνης (ΦΛ), και βελτιστοποιήθηκαν ως προς το μέγεθος και την απόδοση εγκλωβισμού, ώστε να επιλεγεί το καλλίτερο φάρμακο για τη συνέχεια της μελέτης. Επιλέχθηκαν τα λιποσώματα που εγκλώβισαν ΦΛ με τη μέθοδο της ενεργής φόρτωσης (με λιπιδική σύσταση HPC/DPPG/Chol σε μοριακή αναλογία 9/1/10), αφού είχαν τη μέγιστη απόδοση εγκλωβισμού. Αυτά μελετήθηκαν in vitro ως προς τα φυσικοχημικά χαρακτηριστικά τους και ως προς τον ρυθμό απελευθέρωσης του φαρμάκου.Παράλληλα αναπτύχθηκε και ένα ακόμα σύστημα παρατεταμένης αποδέσμευσης: μια θερμοευαίσθητη υδρογέλη με βάση το πολυμερές Pluronic F127, η οποία ενσωμάτωσε λιποσώματα ΦΛ. Μελετήθηκε in vitro ως προς την αποδέσμευση του φαρμάκου με σκοπό τη διερεύνηση της συγκέντρωσης που θα απέδιδε τη βραδύτερη αποδέσμευση.Ως δείγματα αναφοράς και για τα δυο υβριδικά λιποσωμικά συστήματα, χρησιμοποιήθηκε διάλυμα ΦΛ, λιποσώματα ΦΛ και υδρογέλη με διαλυμένη ΦΛ. Η βέλτιστη συγκέντρωση του πολυμερούς ήταν 18% w/v και η in vitro μελέτες τόσο για το λιποσωμικό συσσωμάτωμα όσο και τη λιποσωμική υδρογέλη επιβεβαίωσαν ότι προσδίδουν σημαντικά παρατεταμένη αποδέσμευση σε σχέση με τα σκευάσματα αναφοράς που χρησιμοποιήθηκαν. Η λιποσωμική αποδεσμεύει το 20% του εγκλωβισμένου φαρμάκου σε 24 ώρες, ενώ η λιποσωμική υδρογέλη το 30% στο ίδιο χρονικό διάστημα. Και τα δύο συστήματα αποδέσμευαν μετρήσιμες ποσότητες ΦΛ μέχρι και 120 ώρες.Επιτεύχθηκε λοιπόν η παρασκευή δύο καινοτόμων υβριδικών λιποσωμικών συστημάτων που παρατείνουν σημαντικά το χρόνο παραμονής της φλουρμπιπροφαίνης in vitro, τα οποία είναι κατάλληλα για ενδοφθάλμια χορήγηση.

scholarly journals Experimental design, formulation and in vivo evaluation of a novel topical in situ gel system to treat ocular infections

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248857 ◽  
Author(s):  
Anroop B. Nair ◽  
Jigar Shah ◽  
Shery Jacob ◽  
Bandar E. Al-Dhubiab ◽  
Nagaraja Sreeharsha ◽  
...  
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Adhesive Force ◽  
Gel Strength ◽  
Eye Drops ◽  
Lattice Design ◽  
Ocular Infections ◽  
Gel System

In situ gels have been extensively explored as ocular drug delivery system to enhance bioavailability and efficacy. The objective of present study was to design, formulate and evaluate ion-activated in situ gel to enhance the ocular penetration and therapeutic performance of moxifloxacin in ophthalmic delivery. A simplex lattice design was utilized to examine the effect of various factors on experimental outcomes of the in situ gel system. The influence of polymers (independent variables) such as gellan gum (X1), sodium alginate (X2), and HPMC (X3) on gel strength, adhesive force, viscosity and drug release after 10 h (Q10) were assessed. Selected formulation (MH7) was studied for ex vivo permeation, in vivo irritation and pharmacokinetics in rabbits. Data revealed that increase in concentration of polymers led to higher gel strength, adhesive force and viscosity, however, decreases the drug release. MH7 exhibited all physicochemical properties within acceptable limits and was stable for 6 months. Release profile of moxifloxacin from MH7 was comparable to the check point batches and followed Korsmeyer-Peppas matrix diffusion-controlled mechanism. Ocular irritation study signifies that selected formulation is safe and non-irritant for ophthalmic administration. In vivo pharmacokinetics data indicates significant improvement of moxifloxacin bioavailability (p < 0.0001) from MH7, as evidenced by higher Cmax (727 ± 56 ng/ml) and greater AUC (2881 ± 108 ng h/ml), when compared with commercial eye drops (Cmax; 503 ± 85 ng/ml and AUC; 978 ± 86 ng h/ml). In conclusion, developed in situ gel system (MH7) could offers a more effective and extended ophthalmic therapy of moxifloxacin in ocular infections when compared to conventional eye drops.

scholarly journals Study In Vivo Intraocular Biocompatibility of In Situ Gelation Hydrogels: Poly(2-Ethyl Oxazoline)-Block-Poly(ε-Caprolactone)-Block-Poly(2-Ethyl Oxazoline) Copolymer, Matrigel and Pluronic F127

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e67495 ◽  
Author(s):  
Yih-Shiou Hwang ◽  
Ping-Ray Chiang ◽  
Wei-Hsin Hong ◽  
Chuan-Chin Chiao ◽  
I-Ming Chu ◽  
...  
Keyword(s):  
Pluronic F127 ◽  
In Situ Gelation

scholarly journals Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer

Pharmaceutics ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 15 ◽  
Author(s):  
Li-qian Ci ◽  
Zhi-gang Huang ◽  
Feng-mei Lv ◽  
Jun Wang ◽  
Ling-lin Feng ◽  
...  
Keyword(s):  
Zeta Potential ◽  
Size Distribution ◽  
Ex Vivo ◽  
Pluronic F127 ◽  
Vaginal Mucosa ◽  
In Situ Hydrogel ◽  
Good Potential ◽  
Intravaginal Administration

The present study was carried out to investigate the potential of cationic functionalization on imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion of cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH2) were prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential, and relatively high drug content with the aid of the polydopamine-coating technique. Efficient interaction between NC@PDA-NH2 and mucin was proven by mucin adsorption which was related to the positive zeta-potential value of NC@PDA-NH2 and the change in the size distribution on mixing of NC@PDA-NH2 and mucin. Cellular uptake, growth inhibition, and apoptosis induction in cervicovaginal cancer-related cells demonstrated the superiority of NC@PDA-NH2 over unmodified nanocrystals. For practical intravaginal administration, NC@PDA-NH2 was dispersed in Pluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature and sustained-release profiles. In comparison with unmodified nanocrystals, NC@PDA-NH2 exhibited extended residence on ex vivo murine vaginal mucosa, prolonged in vivo intravaginal residence, and enhanced inhibition on the growth of murine orthotopic cervicovaginal model tumors indicated by smaller tumor size, longer median survival time, and more intratumor apoptosis with negligible mucosal toxicity. In conclusion, cationic functionalization endowed NC@PDA-NH2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer via intravaginal administration.

scholarly journals Design and Optimization of Thermo-reversible Nasal in situ Gel of Atomoxetine Hydrochloride Using Taguchi Orthogonal Array Design

2019 ◽  
Vol 18 (2) ◽  
pp. 183-193 ◽  
Author(s):  
PK Lakshmi ◽  
K Harini
Keyword(s):  
Drug Release ◽  
Residence Time ◽  
Poloxamer 407 ◽  
Release Mechanism ◽  
Gelation Temperature ◽  
In Situ Gel ◽  
Design And Optimization ◽  
Mucoadhesive Polymers ◽  
Carbopol 934P

The present investigation was aimed to develop a thermo-reversible nasal in situ gel of atomoxetine hydrochloride (AH) with reduced nasal muco-ciliary clearance in order to improve residence time and targeting the brain through nasal mucosa for the treatment of attention-deficit hyperactivity disorder (ADHD). In situ gel formulations were prepared using different concentrations of the thermo-gelling poloxamer 407 and mucoadhesive polymers. Temperature-triggered ionic gelation is the mechanism involved. Taguchi L9 OA experimental design was employed for the optimization of the effect of independent variables (Poloxamer 407 and Carbopol 934P) on the response (gelation temperature). In situ gel formulation F4 having 20% poloxamer 407 and 0.3% carbopol 934P and formulation F6 having 20% poloxamer 407 and 0.2% HPMC K100 were optimized based on evaluation parameters. The gelation temperature of F4 and F6 was found to be 37°C ± 0.4 and 37°C ± 0.2, drug content 98.34 and 98.33% and drug release was 83.18, 82.4% in 4 hrs with a flux of 436.9 and 428.1 μg.cm2/hr, respectively. The release pattern of drug followed first-order kinetics with Higuchi release mechanism. The value of ‘n’ from Korsemeyer equation indicated the anomalous diffusional drug release. This study concluded that in situ gel enhanced the nasal residence time and thus may improve the bioavailability of the drug through nasal route by avoiding first pass metabolism Dhaka Univ. J. Pharm. Sci. 18(2): 183-193, 2019 (December)

scholarly journals DEVELOPMENT AND EVALUATION OF AN IN SITU THERMOGELLING SYSTEM OF OFLOXACIN FOR CONTROLLED OCULAR DELIVERY

2019 ◽  
pp. 567-570 ◽  
Author(s):  
ANANTH PRABHU ◽  
MARINA KOLAND
Keyword(s):  
Drug Release ◽  
In Vitro Release ◽  
Methyl Cellulose ◽  
Poloxamer 407 ◽  
Temperature Sensitive ◽  
Gelation Temperature ◽  
Mucoadhesive Polymers ◽  
In Situ Gelling

Objective: The purpose of this study was to develop an in situ ocular gel of ofloxacin which aimed to prolong corneal residence time while controlling drug release. Method: In situ gelling solutions were prepared from Poloxamer 407, a temperature-sensitive gelling polymer and to which, mucoadhesive polymers such as hydroxypropyl methyl cellulose 15 cps and polyvinyl alcohol (PVA) were included to provide corneal adhesion. Drug incorporated gels were prepared and evaluated for their appearance, pH, gelation temperature, and in vitro drug release studies. Results: Incorporation of the drug into the formulation increased the gelation temperature while the addition of mucoadhesive polymers decreased the gelation temperature. Increasing the concentration of bio-adhesive polymers retarded the release of ofloxacin from the poloxamer solutions and drug release was sustained over a period of 9 h. PVA had no significant effect on the gelation temperature and could not sustain the drug release for a longer duration. The in vitro release profiles of the drug from all the formulations could be best expressed by Higuchi’s equation which indicated that gels followed matrix diffusion process and drug release from gel formulations followed first-order process. Conclusion: The results showed that the developed system would be promising in the treatment of ocular infections with the combined advantages of ease of administration, the accuracy of dosing, increased bioavailability, and prolonged retention time.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Three-Dimensional Subcellular Organization of Hepatocytes in Intact Liver: Simultaneous Visualization of Cytoskeletal and Membrane Markers by Confocal Microscopy

1996 ◽  
Vol 54 ◽  
pp. 288-289
Author(s):  
Greg V. Martin ◽  
Ann L. Hubbard
Keyword(s):  
Three Dimensional ◽  
Integral Membrane Proteins ◽  
Polarized Secretion ◽  
Microscope Images ◽  
Computer Aided ◽  
Intracellular Organelles ◽  
Cytoskeletal Elements ◽  
Simultaneous Visualization

The microtubule (MT) cytoskeleton is necessary for many of the polarized functions of hepatocytes. Among the functions dependent on the MT-based cytoskeleton are polarized secretion of proteins, delivery of endocytosed material to lysosomes, and transcytosis of integral plasma membrane (PM) proteins. Although microtubules have been shown to be crucial to the establishment and maintenance of functional and structural polarization in the hepatocyte, little is known about the architecture of the hepatocyte MT cytoskeleton in vivo, particularly with regard to its relationship to PM domains and membranous organelles. Using an in situ extraction technique that preserves both microtubules and cellular membranes, we have developed a protocol for immunofluorescent co-localization of cytoskeletal elements and integral membrane proteins within 20 µm cryosections of fixed rat liver. Computer-aided 3D reconstruction of multi-spectral confocal microscope images was used to visualize the spatial relationships among the MT cytoskeleton, PM domains and intracellular organelles.

Sign in / Sign up

Export Citation Format

Share Document