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

Abstract

RESEARCH ARTICLEDevelopment of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery Maha NasrDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt AbstractThe 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 À23.9 ± 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 mg/cm 2 hr 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.

Recent Strategies in Resveratrol Delivery Systems

“…A different liposomal formulation (PEG‐modified liposomes), was incubated with human erythrocytes and no significant effect was observed, whereas free RSV ethanolic solution caused human red blood cells hemolysis under the same conditions . Similar results were observed with the nanoemulsion coated with HA, that did not cause any tissue damage or epithelial and ciliotoxicity in the nasal mucosa …”

“…In general, the formulations proposed enhanced the penetration and permeation of RSV in comparison with a control solution. For instance, HA coated nanoemulsions confirmed the skin penetration of RSV through ex vivo sheep nasal mucosal and showed a RSV flux of 2.86 μg/cm 2 h …”

“…In these studies ca. 60 % of RSV was released after 6 h at pH 6 through a diffusion‐controlled mechanism (Figure ) …”

“…Otherwise, the RSV bioavailability was analyzed through nasal mucosa and the in vivo quantification in the brain of male Albino rats, showed ca. 7‐fold increase in AUC 0–7 h when the nanoemulsion formulation was used instead of RSV free solution . A drastic increase was observed in RSV uptake in the cerebrospinal fluid of rats using lipidic particles coated with chitosan (8.75 % v/w) in comparison with uncoated particles and pure RSV.…”

Novel Heat-Stable Enterotoxin (STa) Immunogen Based on Cationic Nanoliposomes: Preparation, Characterization and Immunization

“…The morphological features of the cationic STa loaded nanoliposomes were examined using transmission electron microscopy (Jeol, JEM 1010, Tokyo, Japan), after allowing the vesicular sample to be adsorbed onto a carbon coated grid and become negatively stained using 2% uranyl acetate solution [12,22,23].…”