Mucopenetrative Intranasal Cannabinoid Nanoparticles as a Steroid-sparing Approach for Chronic Rhinosinusitis (CRS)

Mehdi Nouraei, PhD
Micellae Delivery Systems

Co-authors: Mehdi Nouraei¹, John J.W. Lee², Amr F. Hamour², Edgar Acosta²
¹Micellae Delivery Systems, ²University of Toronto

Introduction: Chronic rhinosinusitis (CRS) is a chronic inflammatory disorder affecting approximately 10–12% of adults worldwide and is associated with substantial morbidity, impaired quality of life, and significant healthcare utilization. Despite widespread use of intranasal and systemic corticosteroids, many patients remain symptomatic, while prolonged steroid therapy is limited by well-recognized adverse effects. Cannabidiol (CBD) exhibits anti-inflammatory and immunomodulatory properties and represents a promising non-steroidal therapeutic candidate; however, its clinical translation has been limited by poor aqueous solubility and the inability of conventional formulations to effectively penetrate the protective sinonasal mucus barrier.

Methods: A PEG-free, muco-penetrating nanoparticle formulation was engineered to enhance intranasal delivery of CBD across the sinonasal mucus layer while maintaining stable nanoparticle formation following dilution in saline. Therapeutic efficacy was evaluated in an 8-week murine model of CRS. Histopathological outcomes following treatment with intranasal CBD nanoparticles were compared with untreated CRS controls, conventional PEG-based CBD formulations, and intranasal mometasone (gold-standard corticosteroid therapy).

Results: CRS induction produced significant inflammatory and histopathological changes compared with healthy controls. Treatment with muco-penetrating CBD nanoparticles significantly reduced epithelial hyperplasia, epithelial folding, eosinophilic infiltration, hyaline droplets, and Charcot–Leyden crystals compared with untreated CRS mice, with histological evidence of partial restoration of normal respiratory epithelial architecture. Therapeutic outcomes were comparable to those observed with intranasal mometasone, with no significant differences between treatment groups across measured endpoints. In contrast, conventional PEG-based CBD formulations failed to demonstrate comparable therapeutic benefit, despite containing the same active pharmaceutical ingredient. No treatment-related adverse effects or abnormal clinical behavior were observed.

Conclusions: Muco-penetrating intranasal CBD nanoparticles demonstrated therapeutic efficacy comparable to corticosteroid therapy in a murine model of CRS, supporting CBD as a potential steroid-sparing therapeutic strategy. Importantly, the findings demonstrate that successful delivery across the sinonasal mucus barrier is a critical determinant of therapeutic outcome, emphasizing that formulation and drug delivery engineering are enabling components of clinical translation rather than formulation refinements. These results support continued development toward IND-enabling studies and early clinical evaluation.