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

Abstract

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.

Citation

Soliman, M. E., Elmowafy, E., Casettari, L., & Alexander, C. (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), 224-233. https://doi.org/10.1016/j.ijpharm.2018.03.053

• Journal Article Type: Article
• Acceptance Date: Mar 27, 2018
• Online Publication Date: Mar 28, 2018
• Publication Date: May 30, 2018
• Deposit Date: Jun 13, 2018
• Publicly Available Date: Mar 29, 2019
• Journal: International Journal of Pharmaceutics
• Print ISSN: 0378-5173
• Electronic ISSN: 1873-3476
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 543
• Issue: 1-2
• Pages: 224-233
• DOI: https://doi.org/10.1016/j.ijpharm.2018.03.053
• Keywords: Nasal delivery; Thermo-responsive star-shaped polymers; Risedronate; Thermogel cytocompatability; Antiosteoporotic activity
• Public URL: https://nottingham-repository.worktribe.com/output/934917
• Publisher URL: http://dx.doi.org/10.1016/j.ijpharm.2018.03.053
• Contract Date: Jun 13, 2018