A novel thermosensitive in situ hydrogel formulation for sustained intranasal drug delivery
Hanieh Gholizadeh1,2, Juhura G. Almazi3, Dina M. Silva3, Kate Barry2, Ali Fathi4, Simin Maleknia4, Paul Young1,3,5, Daniela Traini1,2, Hui Xin Ong1,2,3
1Respiratory Technology, The Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia
2Macquarie Medical School, Faculty of Medicine, Health, and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia
3Ab Initio Pharma Pty Ltd, Sydney, NSW, Australia
4Tetratherix Technology Pty Ltd, Sydney, NSW, Australia
5Department of Marketing, Business School, Macquarie University, Sydney, NSW 2109, Australia
In this study, a novel synthetic thermosensitive polymer, poly(N-isopropylacrylamide)-co-(polylactide/2-hydroxy methacrylate)- co – (oligo (ethylene glycol), denoted as TP, is presented as a promising drug carrier for sustained intranasal drug delivery. TP is in a liquid state at room temperature, enabling aerosolisation, while it undergoes a phase transition at the physiological temperature to form a hydrogel with a mucoadhesive characteristic that increases the nasal drug residence time, enhancing drug bioavailability. Solutions of TP with varying concentrations (50, 100, and 140 mg/mL) were prepared and found to have desirable spray characteristics and large coverage of the nasal cavity surface area when delivered as a nasal spray. Moreover, the in situ gel formation of TP at 140 mg/mL concentration (TP140) prevented nasal runoff and dripping to the nasopharynx. This is an ideal characteristic of this TP-based formulation as it allows for efficient drug absorption and hence, treatment efficiency. The 98.9% encapsulation efficacy of TP140 for entrapment of ibuprofen (IBU) as a model drug and sustained IBU release from TP140 hydrogel during a 140-hour study showed its suitability as a desirable platform for controlled nasal drug delivery. Furthermore, TP140 did not show any toxic effect on the nasal epithelial cells, suggesting its safety as an excipient in nasal formulations.
The proposed in situ TP thermosensitive gel nasal formulation is shown to be readily delivered as a nasal spray and expresses mucoadhesive characteristics upon delivery to the nose, where it retains the drug for a longer time and enables sustained drug release.