Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery

Abstract

The development of mucoadhesive lipidic nanoemulsion based on hyaluronic acid, co-encapsulating two polyphenols (resveratrol and curcumin) for the transnasal treatment of neurodegenerative diseases was attempted in the current manuscript. Nanoemulsions were prepared by the spontaneous emulsification method, and were characterized for their particle size, zeta potential, mucoadhesive strength and morphology. The selected formula was tested for its antioxidant potential, in vitro and ex vivo release of the two polyphenols, safety on nasal mucosa and in vivo quantification of the two drugs in rat brains. Its stability was tested by monitoring the change in particle size, zeta potential, drugs' content and antioxidant potential upon storage for 3 months. The optimized hyaluronic acid based nanoemulsion formula displayed a particle size of 115.2 ± 0.15 and a zeta potential of −23.9 ± 1.7. The formula displayed a spherical morphology and significantly higher mucoadhesive strength compared to its non mucoadhesive counterpart. In addition, the nanoemulsion was able to preserve the antioxidant ability of the two polyphenols and protect them from degradation. Diffusion controlled release of the two drugs was achievable till 6 hours, with an ex vivo flux across sheep nasal mucosa of 2.86 and 2.09 µg/cm²hr for resveratrol and curcumin, respectively. Moreover, the mucoadhesive nanoemulsion was safe on nasal mucosa and managed to increase the amounts of the two polypehnols in the brain (about 7 and 9 folds increase in AUC_0–7 h for resveratrol and curcumin, respectively). Hyaluronic acid based lipidic nanoemulsion proved itself as a successful carrier enhancing the solubility, stability and brain targetability of polyphenols.

• Curcumin
• intranasal
• neurodegenerative
• resveratrol
• stability

Acknowledgements

The author would like to thank Gattefosse' Company (France) for their kind supply of Labrafac Lipophile WL 1349 and Labrafac PG. The author would also like to thank BASF Company (Germany) for their kind supply of Cremophor RH. In addition, special thanks to Shandong Freda Biopharm Company for their kind supply of hyaluronic acid. The author is also thankful to Professor Adel Bakir (Faculty of Veterinary medicine, Cairo University) for his help in the histopathological examination of the nasal samples.

Declaration of interest

The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or a financial conflict with anything related to the manuscript. No writing assistance was utilized in the production of the manuscript. The author reports no other conflicts of interest in this work.