EventsThe 2nd International Electronic Conference on Medicinal Chemistry and Pharmaceutics
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Published
This submission belongs to the session S9. Formulation, Drug Delivery, and Controlled Release of the event The 2nd International Electronic Conference on Medicinal Chemistry and Pharmaceutics
Published date
28 Oct, 2026
Academic Editor
author-avatarAlfredo Berzal-Herranz
Citation
Joana Torres, Gonçalo Farias, Nathalie Hauchard, Yoni Effosse, Domingos Carvalho Ferreira, Inês Silva Costa, Renata Silva, Ana Catarina Silva, Olfactory deposition of Ibuprofen/Zolmitriptan‑Loaded NLCs for Targeted Migraine Therapy, in Proceedings of The 2nd International Electronic Conference on Medicinal Chemistry and Pharmaceutics, 1 November–30 November 2026, MDPI: Basel, Switzerland
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Olfactory deposition of Ibuprofen/Zolmitriptan‑Loaded NLCs for Targeted Migraine Therapy

Joana Torres 1,2
Gonçalo Farias 3
Nathalie Hauchard 3
Yoni Effosse 3
Domingos Carvalho Ferreira 1,2
Inês Silva Costa 2,4
Renata Silva 2,4
image
Ana Catarina Silva 1,2,5
1. MEDTECH - Pharmaceutical Technology Laboratory, Faculty of Pharmacy, University of Porto, Porto, 4050-313, Portugal
2. UCIBIO i4HB, Faculty of Pharmacy, University of Porto, Porto, 4050-313, Portugal
3. Aptar Pharma, Aptar Pharma, Le Vaudreuil, 27100, France
4. Toxicology Laboratory, Faculty of Pharmacy, University of Porto, Porto, 4050-313, Portugal
5. FP-BHS (Biomedical and Health Sciences Research Unit), FP-I3ID (Instituto de Investigação, Inovação e Desenvolvimento), Faculty of Health Sciences, University Fernando Pessoa, Porto, 4200-150, Portugal
Abstract

Introduction: Migraine is a neurological disorder and current treatments often provide incomplete relief due to limited brain targeting. In this context, combining drugs and delivering them through the nose‑to‑brain route, which may facilitate access to the brain following deposition in the olfactory region, may improve therapeutic performance, particularly when supported by nanostructured lipid carriers (NLCs). This work aimed to develop a combined Ibuprofen/Zolmitriptan‑loaded NLC formulation and evaluate its cytotoxicity and olfactory deposition in vitro.

Methods: The Ibuprofen/Zolmitriptan‑loaded NLC was obtained by mixing the two previously optimised formulations (IBU‑loaded and ZOL‑loaded NLC), which were characterised for particle size (PS), polydispersity index (PDI), zeta potential (ZP) and encapsulation efficiency (EE). Cytotoxicity was assessed in differentiated neuronal SH‑SY5Y cells. Olfactory deposition was evaluated in the 3D‑printed nasal cast Aeronose® using four Aptar Pharma nasal spray devices (Neurospray™, Neurospray™ Preservative-Free, Cerespray™ Next-Gen and VP7/100+232).

Results: The Ibuprofen/Zolmitriptan‑loaded NLC showed a PS of 98.980 ± 0.249 nm, a PDI of 0.242 ± 0.002 and a ZP of -15.143 ± 0.844 mV, with an EE of 84.376 ± 1.594 % for ibuprofen and 74.231 ± 0.646 % for zolmitriptan, demonstrating characteristics suitable for nose-to-brain delivery. The formulation showed no significant cytotoxicity up to 100 µg/mL in SH-SY5Y cells. Deposition studies revealed that the Neurospray™ achieved the highest deposition of the NLC formulation in the olfactory region (67.62 %), followed by the Neurospray™ Preservative-Free (64.34 %), Cerespray™ Next-Gen (52.63 %) and VP7/100+232 (14.80 %).

Conclusion: The Ibuprofen/Zolmitriptan‑loaded NLC exhibited suitable characteristics and high olfactory deposition when administered using the Neurospray™ device, supporting its potential for nose‑to‑brain delivery in acute migraine therapy.

Keywords
Acute migraine
Combination therapy
Ibuprofen
Zolmitriptan
Nanostructured lipid carriers (NLC)
Nose-to-brain delivery
Olfactory deposition
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