Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study

Abstract

Chitosan (CS) nanoparticles of thymoquinone (TQ) were prepared by the ionic gelation method and are characterized on the basis of surface morphology, in vitro or ex vivo release, dynamic light scattering, and X-ray diffractometry (XRD) studies. Dynamic laser light scattering and transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. The results showed that the particle size of the formulation was significantly affected by the drug:CS ratio, whereas it was least significantly affected by the tripolyphosphate:CS ratio. The entrapment efficiency and loading capacity of TQ was found to be 63.3% ± 3.5% and 31.23% ± 3.14%, respectively. The drug-entrapment efficiency and drug-loading capacity of the nanoparticles appears to be inversely proportional to the drug:CS ratio. An XRD study proves that TQ dispersed in the nanoparticles changes its form from crystalline to amorphous. This was further confirmed by differential scanning calorimetry thermography. The flat thermogram of the nanoparticle data indicated that TQ formed a molecular dispersion within the nanoparticles. Optimized nanoparticles were evaluated further with the help of scintigraphy imaging, which ascertains the uptake of drug into the brain. Based on maximum concentration, time-to-maximum concentration, area-under-curve over 24 hours, and elimination rate constant, intranasal TQ-loaded nanoparticles (TQ-NP1) proved more effective in brain targeting compared to intravenous and intranasal TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the mucoadhesive properties of TQ-NP1.

The nasal delivery of nanoencapsulated statins – an approach for brain delivery

“…Gamma scintigraphy was selected as a powerful and rapid method to evaluate the biodistribution of the formulation after nasal administration in rodents. 76 A suspension of simvastatin was used as a control. It is worth pointing out that the radioactivity that is detected cannot be considered permanently bound to the particles or to the drug molecule.…”

Pharmacological, toxicological and neuronal localization assessment of galantamine/chitosan complex nanoparticles in rats: future potential contribution in Alzheimer’s disease management

“…The aforementioned elevation in the percentage change of serum urea and creatinine in the nasal GH solution group might be due to the leakage of a fraction of the nasally administered GH solution to systemic blood circulation via nasal mucosa. However, negligible drug leakage is expected upon applying nasal CX-NP2 because of their mucoadhesiveness (Alam et al, 2012;Md et al, 2013). As it has not been reported previously that GH oral administration might have such elevating effect on serum urea and creatinine levels, the explanation of these results requires further investigation.…”

“…This might be due to the leakage of a fraction of the nasally administered GH solution to systemic blood circulation via nasal mucosa. The aforementioned leakage is thought to be negligible in case of nasal CX-NP2 because of their superior mucoadhesiveness and permeation to CNS directly (Alam et al, 2012;Md et al, 2013).…”

Physicochemical Properties and Control Release of Aloe Vera (Aloe barbadensis Miller) Bioactive Loaded Poly (Lactic Co-Glycolide Acid) Synthesized Nanoparticles

“…The EE values for the FDG loaded NP was much higher due to the increased concentration of the bioactive compounds due to freeze drying. Alam et al [28] reported 63% for TQ-chitosin NP whereas 90% was reported for TQ-liposome NP [29]. Many factors influences the control and regulation of the EE such as the: entrapped material, polymer molecular weight, and lactide: glycolide ratio [30] [31] [32], likewise the interaction between the hydroxyl group of the active compound and carboxyl group of the PLGA.…”