Intranasal Delivery of Granisetron to the Brain via Nanostructured Cubosomes-Based In Situ Gel for Improved Management of Chemotherapy-Induced Emesis

Essam M Eissa; Mohammed H Elkomy; Hussein M Eid; Adel A Ali; Mohammed A S Abourehab; Amal M Alsubaiyel; Ibrahim A Naguib; Izzeddin Alsalahat; Amira H Hassan

doi:10.3390/pharmaceutics14071374

Intranasal Delivery of Granisetron to the Brain via Nanostructured Cubosomes-Based In Situ Gel for Improved Management of Chemotherapy-Induced Emesis

Pharmaceutics. 2022 Jun 29;14(7):1374. doi: 10.3390/pharmaceutics14071374.

Authors

Essam M Eissa¹, Mohammed H Elkomy², Hussein M Eid¹, Adel A Ali¹, Mohammed A S Abourehab^{3

4}, Amal M Alsubaiyel⁵, Ibrahim A Naguib⁶, Izzeddin Alsalahat⁷, Amira H Hassan¹

Affiliations

¹ Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt.
² Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia.
³ Department of Pharmaceutics, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
⁴ Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
⁵ Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif 21944, Saudi Arabia.
⁷ UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff CF24 1TP, UK.

Abstract

This research aimed to boost granisetron (GS) delivery to the brain via the intranasal route to better manage chemotherapy-induced emesis. Glycerol monooleate (GMO), Poloxamer 407 (P 407) and Tween 80 (T 80) were used to formulate GS-loaded cubosomes (GS-CBS) utilizing a melt dispersion-emulsification technique. GS-CBS were characterized by testing particle diameter, surface charge and entrapment efficiency. The formulations were optimized using a Box-Behnken statistical design, and the optimum formula (including GMO with a concentration of 4.9%, P 407 with a concentration of 10%, and T 80 with a concentration of 1%) was investigated for morphology, release behavior, ex vivo permeation through the nasal mucosa, and physical stability. Moreover, the optimal formula was incorporated into a thermosensitive gel and subjected to histopathological and in vivo biodistribution experiments. It demonstrated sustained release characteristics, increased ex vivo permeability and improved physical stability. Moreover, the cubosomal in situ gel was safe and biocompatible when applied to the nasal mucosa. Furthermore, compared to a drug solution, the nose-to-brain pathway enhanced bioavailability and brain distribution. Finally, the cubosomal in situ gel may be a potential nanocarrier for GS delivery to the brain through nose-to-brain pathway.

Keywords: biodistribution; brain targeting; cubosomes; granisetron; in situ gel; intranasal; pharmacokinetics.

Grants and funding

The authors would like to thank the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant Code: (22UQU4290565DSR33). Additionally, the authors would like to extend their sincere appreciation to Taif University Researchers Supporting Project number (TURSP-2020/56), Taif University, Taif, Saudi Arabia.