Passive Targeted Drug Delivery of Venlafaxine HCl to the Brain by Modified Chitosan Nanoparticles: Characterization, Cellular Safety Assessment, and In Vivo Evaluation.

Purposes: Generalized anxiety is one of the most frequent anxiety problems. This study aimed to improve the distribution of venlafaxine HCl (Ven) in the brain by using Tween 80-coated chitosan nanoparticles made by ionic gelation. Methods: The impact of the proportion of chitosan (CS): tripolyphosphate (TPP) and surface coating on the formulations were investigated. Differential scanning calorimetry (DSC), attenuated total reflectance–Fourier transform infrared (ATR-FTIR) spectroscopy, drug release, scanning electron microscopy (SEM), and animal bio-distribution model, and cellular safety assessment were applied to investigate the characteristics, morphology, and effectiveness of the Ven nanoparticle. Results: The drug entrapment efficiency (80.69 ± 1.91%), particle size (248.066 ± 7.385 nm), polydispersity index (0.286 ± 0.012), and zeta potential (-13.93 ± 1.65 mV) of Tween 80-coated and Ven-incorporated chitosan nanoparticles were determined to be adequate. In vitro drug release from uncoated (62.758 ± 3.581%) and Tween 80-coated nanoparticles (30.682 ± 3.225%) demonstrated sustained release over 24 h compared with Ven solution. Furthermore, the cell safety of both coated and uncoated nanoparticles showed that they were nontoxic. In vivo bio-distribution investigations in mice revealed that Tween 80-coated Ven-entrapped chitosan nanoparticles had greater Ven amounts (474.393 ± 52.100 ng/ml) in the brain tissue after 1 h of oral administration than uncoated Ven-entrapped chitosan nanoparticles (357.815 ± 39.624 ng/ml) and Ven solution (122.752 ± 38.075 ng/ml). Conclusion: These findings indicated that surface-coated, Ven-loaded chitosan nanoparticles might become a viable technique for improving Ven brain uptake and ultimately opening up new pathways for generalized anxiety disorder management. [ABSTRACT FROM AUTHOR]