The constant release of neurotrophic factors through a nanomaterial-based delivery system can be an important strategy in medical and pharmaceutical fields for nerve tissue engineering. The present study was aimed at encapsulating NGF and AuNP5 in chitosan nanoparticles (NGF-CNPs and AuNPs-CSNPs) and its evaluation on the differentiation potential of human adipose-derived stem cells (h-ADSCs) to Schwann-like cells. The NGF-CNPs were prepared by ionotropic gelation method with tripolyphosphate (TPP) as a crosslinker. After synthesis and characterization of nanoparticles, NGF encapsulation efficiency and release profile were observed by Bradford assay. Next, the effects of NGF-CSNPs and AuNPs-CSNPs on h-ADSCs survival were assessed through MTT assay. Also, the efficacy of Schwann-like cells differentiation was assessed by immunocytochemistry and real-time RT-PCR for S100 beta and MBP markers. NGF encapsulation efficiency was found about 85% and controlled and sustained release of NGF was observed during 7 days in vitro (74.63 +/- 2.07%). The findings revealed that these nanoparticles are cytocompatible. The immunocytochemical analysis indicated that NGF-CSNPs and AuNPs-CSNPs could significantly increase the differentiated rate and myelinogenic potential of Schwann-like cells (p < 0.05). Besides, the expression level of GFAP, S100 beta, and MBP demonstrated significant upregulation in NGF-CSNPs and AuNPs-CSNPs groups compared to the control group (p < 0.05). Hence, it can be proposed that NGF-CNPs and AuNPs-CSNPs are capable of controlled release with improving the ability of h-ADSCs differentiation to Schwann-like cells. Also, the results show the potential future application of this differentiation in nerve tissue regeneration. (C) 2019 Elsevier Inc. All rights reserved.