Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery

The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing ei...

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Main Authors: Soliman, Mahmoud E., Elmowafy, Enas, Casettari, Luca, Alexander, Cameron
Format: Article
Published: Elsevier 2018
Subjects:
Online Access:https://eprints.nottingham.ac.uk/52380/
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author Soliman, Mahmoud E.
Elmowafy, Enas
Casettari, Luca
Alexander, Cameron
author_facet Soliman, Mahmoud E.
Elmowafy, Enas
Casettari, Luca
Alexander, Cameron
author_sort Soliman, Mahmoud E.
building Nottingham Research Data Repository
collection Online Access
description The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37 °C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in situ gels should have promising application as nasal drug delivery systems.
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spelling nottingham-523802020-05-04T19:38:17Z https://eprints.nottingham.ac.uk/52380/ Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery Soliman, Mahmoud E. Elmowafy, Enas Casettari, Luca Alexander, Cameron The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37 °C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in situ gels should have promising application as nasal drug delivery systems. Elsevier 2018-05-30 Article PeerReviewed Soliman, Mahmoud E., Elmowafy, Enas, Casettari, Luca and Alexander, Cameron (2018) Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery. International Journal of Pharmaceutics, 543 (1-2). pp. 224-233. ISSN 1873-3476 Nasal delivery; Thermo-responsive star-shaped polymers; Risedronate; Thermogel cytocompatability; Antiosteoporotic activity http://dx.doi.org/10.1016/j.ijpharm.2018.03.053 doi:10.1016/j.ijpharm.2018.03.053 doi:10.1016/j.ijpharm.2018.03.053
spellingShingle Nasal delivery; Thermo-responsive star-shaped polymers; Risedronate; Thermogel cytocompatability; Antiosteoporotic activity
Soliman, Mahmoud E.
Elmowafy, Enas
Casettari, Luca
Alexander, Cameron
Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
title Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
title_full Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
title_fullStr Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
title_full_unstemmed Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
title_short Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
title_sort star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
topic Nasal delivery; Thermo-responsive star-shaped polymers; Risedronate; Thermogel cytocompatability; Antiosteoporotic activity
url https://eprints.nottingham.ac.uk/52380/
https://eprints.nottingham.ac.uk/52380/
https://eprints.nottingham.ac.uk/52380/