Summary
Intranasal mRNA administration is an attractive treatment modality for many diseases, including brain tumours and neurodegenerative diseases. In this study, a novel proprietary synthetic thermosensitive polymer, denoted as TP, is presented as a promising alternative drug carrier for nasal delivery of mRNA. TP has a thermogelling property, it remains in liquid state at room temperature and undergoes a phase transition to form a hydrogel with a mucoadhesive characteristic at physiological temperature. A series of studies was conducted to characterise the interaction of mRNA, coding the enhanced green fluorescent protein (EGFP), with TP to demonstrate the potential of the polymer to form nanoparticles for the intranasal administration of mRNA therapeutics. Two concentrations of TP solutions (25 mg/mL- TP25 and 35 mg/mL-TP35) were formulated with EGFP and lipofectamine lipids and was found to generate nanoparticles of approximately 40 nm. The TP formulations were also able to stabilise mRNA lipofectamine particles for at least 7 days at ambient conditions and displaying EGFP mRNA expression similar to that of the positive control, fresh mRNA formulation. When the formulation was aerosolised using the Bivax nasal spray device (Aptar), the aerosol particle size distribution was larger in formulations containing the TP polymer. Nevertheless, the formulations are appropriate for nasal delivery as most of the aerosols are above 10µm. Additionally, deposition of the 250 µL spray of TP25 and TP35 formulations was successful, while the control without the carrier showed significant nasal dripping. This further demonstrates the suitability of TP25 and TP35 as alternative drug carrier polymers.