Improving glioblastoma therapeutic outcomes via doxorubicin-loaded nanomicelles modified with borneol

• Published in: International journal of pharmaceutics 2019-08, Vol.567, p.118485-118485, Article 118485
• Main Authors: Meng, Lingwei, Chu, Xiaoyang, Xing, Haoyue, Liu, Xuan, Xin, Xin, Chen, Liqing, Jin, Mingji, Guan, Youyan, Huang, Wei, Gao, Zhonggao
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - chemistry; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Borneol; Brain Neoplasms - drug therapy; Camphanes - administration & dosage; Camphanes - chemistry; Cell Line; Cell Survival - drug effects; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Drug Liberation; Glioblastoma; Glioblastoma - drug therapy; Humans; Male; Mice, Inbred ICR; Micelles; Nanomicelle; Nanostructures - administration & dosage; Nanostructures - chemistry; Rats; Tumor therapy; Wound Healing - drug effects
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.118485

Borneol (BO) was firstly conjugated with DSPE-PEG2000-COOH to synthesize a novel carrier DSPE-PEG2000-BO to enhance the delivery of doxorubicin (DOX) into brain for glioblastoma therapy. BO-modified nanomicelles loading doxorubicin (DOX BO-PMs) were prepared using DSPE-PEG2000-BO and investigated thoroughly. DOX BO-PMs significantly enhanced the transport efficiency of DOX across blood-brain barrier (BBB) and also showed a quick accumulation in brain. More importantly, DOX BO-PMs exhibited the significant inhibition effect on the tumor growth and metastasis in the mouse glioblastoma model. DOX BO-PMs can improve the therapeutic outcomes of glioblastoma and become a promising nanodrug candidate for the application of doxorubicin in the field of glioblastoma therapy. [Display omitted] Glioblastoma is a grade IV malignant glioma with high recurrence and metastasis and faces a therapeutic obstacle that the blood-brain barrier (BBB) severely hinders the brain entry and efficacy of therapeutic drugs. Previous studies suggest that borneol (BO) has been used to enhance interested drugs to penetrate the BBB. In this study, a borneol-modified nanomicelle delivery system was established to facilitate the brain entry of doxorubicin for glioblastoma therapy. Herein, we firstly conjugated borneol molecules with DSPE-PEG2000-COOH to synthesize a novel carrier DSPE-PEG2000-BO and also characterized its structure. Doxorubicin-loaded nanomicelles (DOX BO-PMs) were prepared using DSPE-PEG2000-BO via electrostatic interaction and the physicochemical properties were investigated. The average particle size and zeta potential of DOX BO-PMs were respectively (14.95 ± 0.17)nm and (−1.27 ± 0.06)mV, and the drug encapsulation efficiency and loading capacity in DOX BO-PMs were (95.69 ± 0.49)% and (14.62 ± 0.39)%, respectively. The drug release of the DOX BO-PMs exhibited a both time- and pH-dependent pattern. The results demonstrated that DOX BO-PMs significantly enhanced the transport efficiency of DOX across the BBB and also exhibited a quick accumulation in the brain tissues. The in vitro anti-proliferation assay results suggested that DOX BO-PMs exerted a strong inhibitory effect on proliferation of glioblastoma cells. Importantly, in vivo antitumor results demonstrated that DOX BO-PMs significantly inhibited the tumor growth and metastasis of glioblastoma. In conclusion, DOX BO-PMs can improve the glioblastoma therapeutic outcomes and become a promising nanodrug candidate for th