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

PurposesGeneralized 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.MethodsThe 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.ResultsThe 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).ConclusionThese 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.