In situ nanostructured hydrogel of resveratrol for brain targeting: in vitro-in vivo characterization

Abstract

The purpose of conducting the present research work was to develop resveratrol nanostructured in situ gel for the treatment of Alzheimer's disease. Resveratrol loaded lipid carrier was prepared by melt emulsification-probe sonication method, and the final product was evaluated for particle size (132 ± 11.90 nm), polydispersity index (0.209 ± 0.005), zeta potential (- 23 ± 3.79 mV), drug loading (9.26 ± 3.79%), and entrapment efficiency (74 ± 11.40%). Following incorporation of the resveratrol nanostructured lipid carrier in gellan gum and xanthan gum, in situ gel was formulated and characterized. The optimized in situ gel showed fivefold higher permeation across the nasal mucosa as compared to resveratrol suspension-based in situ gel. Finally, optimized in situ gel was evaluated using in vivo pharmacodynamic study by the scopolamine-induced amnesia model in rats using Morris Water Maze test. It showed significant improvement in memory function in rats treated with optimized in situ gel as compared to orally administered resveratrol suspension. The enhanced permeation across nasal mucosa and improved memory function suggest that the resveratrol nanostructured lipid carrier-based in situ gel could be an effective and promising approach for the treatment of Alzheimer's disease.

Biomaterials in Neurodegenerative Disorders: A Promising Therapeutic Approach

“…In AD, the studies focused mainly on drug delivery. Peptide-amphiphile hydrogels have been studied for the release of the antioxidant and neuroprotective compound curcumin [60] and hydrogels made of gellan gum and xanthan gum for the release of Resveratrol [61]. The encapsulation of VEGF-secreting fibroblasts into alginate reduced amyloid-β deposition in APP/PS1 mouse models.…”

Nose-to-Brain Delivery of Antioxidants as a Potential Tool for the Therapy of Neurological Diseases

“…A nanostructured lipid carrier formulation based on cetyl-palmitate, Capmul MCM, and Acrysol K150, containing resveratrol and designed for nasal administration has been proposed by Rajput et al [30]. The nanoparticles were prepared by the melt emulsification-probe sonication method.…”

“…Often, the formulations proposed involve the addition of a mucoadhesive polymer to overcome the problem of nasal clearance [31,35,36,[38][39][40][41]44,101,102]. Lipidic excipients are frequently used both for the preparation of lipidic nanoparticles [27,30,31,43] and as components of nanoemulsions [33,34,36,39,41]. The importance of the lipidic excipients in the design of intranasal formulations is confirmed by the literature [103], and it is probably based on the improvement of solubilization and loading of hydrophobic molecules and on the hydrophilic/lipophilic nature of the barriers present in the nose-to-brain pathways.…”

Natural Polysaccharide Carriers in Brain Delivery: Challenge and Perspective

“…REV was also loaded in lipid carrier and nanostructured in GLG and XG [116]. The resulting in situ gel was formulated and characterized, obtaining a fivefold higher permeation across the nasal mucosa compared to REV suspension-based in situ gel.…”