Hui Song, Man Wei, Nan Zhang, He Li, Xiaochuan Tan, Yujia Zhang, Wensheng Zheng Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Introduction: The incidence of central nervous system disease has increased in recent years. However, the transportation of drug is restricted by the blood–brain barrier, contributing to the poor therapeutic effect in the brain. Therefore, the development of a new brain-targeting drug delivery system has become the hotspot of pharmacy. Materials and methods: Borneol, a simple bicyclic monoterpene extracted from Dryobalanops aromatica, can direct drugs to the upper body parts according to the theory of traditional Chinese medicine. Dioleoyl phosphoethanolamine (DOPE) was chemically modified by borneol as one of the lipid materials of solid lipid nanoparticle (SLN) in the present study. Results: The borneol-modified chemically solid lipid nanoparticle (BO-SLN/CM), borneol-modified physically solid lipid nanoparticle (BO-SLN/PM), and SLN have similar diameter (of about 87 nm) and morphological characteristics. However, BO-SLN/CM has a lower cytotoxicity, higher cell uptake, and better blood–brain barrier permeability compared with BO-SLN/PM and SLN. BO-SLN/CM has a remarkable targeting function to the brain, while BO-SLN/PM and SLNs are concentrated at the lung. Conclusion: The present study provides an excellent drug delivery carrier, BO-SLN/CM, having the application potential of targeting to the brain and permeating to the blood–brain barrier. Keywords: blood–brain barrier, solid lipid nanoparticle, phospholipid modification, BBB model in vitro, body distribution