Posted by Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts the entry of external substances into the brain tissue. Consequently, finding ways to overcome the limited therapeutic effect imposed by the BBB has become a central goal in advancing delivery systems targeted to the brain. In this context, the intranasal route has emerged as a promising solution for delivering treatments directly from the nose to the brain through the olfactory and trigeminal nerve pathways and thus, bypassing the BBB. The use of lipid-based nanoparticles, including nano/microemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, has shown promise in enhancing the efficiency of nose-to-brain delivery. These nanoparticles facilitate drug absorption from the nasal membrane. Additionally, the in situ gel (ISG) system has gained attention owing to its ability to extend the retention time of administered formulations within the nasal cavity. When combined with lipid-based nanoparticles, the ISG system creates a synergistic effect, further enhancing the overall effectiveness of brain-targeted delivery strategies. This comprehensive review [1] provides a thorough investigation of intranasal administration. It delves into the strengths and limitations of this specific delivery route by considering the anatomical complexities and influential factors that play a role during dosing. Furthermore, this study introduces strategic approaches for incorporating nanoparticles and ISG delivery within the framework of intranasal applications. Finally, the review provides recent information on approved products and the clinical trial status of products related to intranasal administration, along with the inclusion of quality-by-design–related insights.
Cyclodextrins are mentioned only as possible additives to improve the drug solubility but no examples are mentioned. Here are some recent examples for in situ forming gels applied for nasal delivery from the literature:
- Hyaluronic Acid-Incorporated Thermosensitive Nasal in situ Gel of Meclizine Hydrochloride with HPBCD [2]
- Gellan Gum-based Nasal In-situ Gel Formulation of Fexofenadine HCl with BCD [3]
- Poloxamer-based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam with HPBCD [4]
References
- Koo J, Lim C, Oh KT. Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations. Int J Nanomedicine. 2024;19:1767-1807. https://doi.org/10.2147/IJN.S439181
- Obayes, K. K., & Thomas, L. M. (2024). Development and Characterization of Hyaluronic Acid-Incorporated Thermosensitive Nasal in situ Gel of Meclizine Hydrochloride. Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), 6(1), 97–104. https://doi.org/10.54133/ajms.v6i1.499
- Amarsing, T.S., Pandit, P.S. (2023) Development of Nasal In-situ Gel Formulation of Fexofenadine HCl Using Gellan Gum (Gelerite®). International Journal of Pharmaceutical Quality Assurance, 14(1), pp. 1–3. https://impactfactor.org/PDF/IJPQA/14/IJPQA,Vol14,Issue1,Article10.pdf
- Cirri, M.; Maestrelli, F.; Nerli, G.; Mennini, N.; D’Ambrosio, M.; Luceri, C.; Mura, P.A. (2021) Development of a Cyclodextrin-Based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam Intranasal Delivery. Pharmaceutics 13, 969. https://doi.org/10.3390/pharmaceutics13070969