Resveratrol is a promising neuroprotective agent against neurodegenerative disorders such as Alzheimer's disease. Resveratrol-loaded transferosomes and nanoemulsions were developed and labelled with gold nanoparticles (GNPs). The water maze test was utilized to identify the effect on spatial memory recovery. The treated rats were examined for cellular uptake and bioaccumulation of drug in the brain using computed tomography and histopathological examination utilizing GNPs as a biomarker. Compared to nanoemulsions, transferosomes displayed higher permeation of up to 81.29 ± 2.64% and higher fluorescence intensity with p < 0.05. Transferosomes significantly enhanced behavioural acquisition and spatial memory function in the amnesic rats compared to both the nanoemulsion formulation and the pure drug. Computed tomography effectively demonstrated the accumulation of GNPs in the brains of all treated rats, while superior accumulation of GNPs was observed in the rats that received the transferosome formulation. The histopathology also demonstrated GNP accumulation in the nuclei and cytoplasm in the brain tissues of both the transferosome- and nanoemulsion-treated groups. Therefore, the developed transferosomes may be considered as a well-designed brain targeting system that might further be applied for targeting many drugs to be used in the treatment of central nervous system diseases.

Nano-emulgel has become one of the most significant controlled release systems, which has the advantages of both gels and nano-emulsions. This work aims at the formulation of nasal nano-emulgel for resveratrol, employing carbopol 934 and poloxamer 407 as the gelling agents. The optimum nano-emulsion was determined through further characterization of the selected system. The nasal nano-emulgel was prepared and tested for the in vitro release, the release kinetics, FTIR, ex vivo permeation, nasal mucosa toxicity, and in vivo pharmacokinetic study. The optimum nano-emulsion consisted of Tween 20, Capryol 90, and Transcutol at a ratio of (54.26: 23.81: 21.93%v/v), and it exhibited transmittance of 100%, resveratrol solubility of 159.9 ± 6.4 mg/mL, globule size of 30.65 nm. The in vitro resveratrol released from nano-emulsion and nasal nano-emulgel was 96.17 ± 4.43% and 78.53 ± 4.7%, respectively. Ex vivo permeation was sustained during 12 h up to 63.95 ± 4.7%. The histopathological study demonstrated that the formula is safe and tolerable to the nasal mucosa. C_max and AUC _(0–∞) of resveratrol obtained after nasal administration of nasal nano-emulgel was 2.23 and 8.05 times, respectively. Similarly, T_max was increased up to 3.67 ± 0.82 h. The optimized nasal nano-emulgel established intranasal safety and bioavailability enhancement so it is considered as a well-designed system to target the brain.