Yiran Yan1, Yan Chen2, Zhongxun Liu1, Feiyan Cai3, Wanting Niu4,5, Liming Song1, Haifeng Liang1, Zhiwen Su1, Bo Yu1, Fei Yan6. 1. Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China. 2. Department of Ultrasonic Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China. 3. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People's Republic of China. 4. VA Boston Healthcare System, Boston, MA, 02130, USA. 5. Department of Orthopedics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. 6. CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People's Republic of China.
Abstract
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder. Owing to the presence of blood-brain barrier (BBB), conventional pharmaceutical agents are difficult to the diseased nuclei and exert their action to inhibit or delay the progress of PD. Recent literatures have demonstrated that curcumin shows the great potential to treat PD. However, its applications are still difficult in vivo due to its poor druggability and low bioavailability through the BBB. METHODS: Melt-crystallization methods were used to improve the solubility of curcumin, and curcumin-loaded lipid-PLGA nanobubbles (Cur-NBs) were fabricated through encapsulating the curcumin into the cavity of lipid-PLGA nanobubbles. The bubble size, zeta potentials, ultrasound imaging capability and drug encapsulation efficiency of the Cur-NBs were characterized by a series of analytical methods. Low-intensity focused ultrasound (LIFU) combined with Cur-NB was used to open the BBB to facilitate curcumin delivery into the deep brain of PD mice, followed by behavioral evaluation for the treatment efficacy. RESULTS: The solubility of curcumin was improved by melt-crystallization methods, with 2627-fold higher than pure curcumin. The resulting Cur-NBs have a nanoscale size about 400 nm and show excellent contrast imaging performance. Curcumin drugs encapsulated into Cur-NBs could be effectively released when Cur-NBs were irradiated by LIFU at the optimized acoustic pressure, achieving 30% cumulative release rate within 6 h. Importantly, Cur-NBs combined with LIFU can open the BBB and locally deliver the curcumin into the deep-seated brain nuclei, significantly enhancing efficacy of curcumin in the Parkinson C57BL/6J mice model in comparison with only Cur-NBs and LIFU groups. CONCLUSION: In this work, we greatly improved the solubility of curcumin and developed Cur-NBs for brain delivery of curcumin against PD through combining with LIFU-mediating BBB. Cur-NBs provide a platform for these potential drugs which are difficult to cross the BBB to treat PD disease or other central nervous system (CNS) diseases.
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder. Owing to the presence of blood-brain barrier (BBB), conventional pharmaceutical agents are difficult to the diseased nuclei and exert their action to inhibit or delay the progress of PD. Recent literatures have demonstrated that curcumin shows the great potential to treat PD. However, its applications are still difficult in vivo due to its poor druggability and low bioavailability through the BBB. METHODS: Melt-crystallization methods were used to improve the solubility of curcumin, and curcumin-loaded lipid-PLGA nanobubbles (Cur-NBs) were fabricated through encapsulating the curcumin into the cavity of lipid-PLGA nanobubbles. The bubble size, zeta potentials, ultrasound imaging capability and drug encapsulation efficiency of the Cur-NBs were characterized by a series of analytical methods. Low-intensity focused ultrasound (LIFU) combined with Cur-NB was used to open the BBB to facilitate curcumin delivery into the deep brain of PD mice, followed by behavioral evaluation for the treatment efficacy. RESULTS: The solubility of curcumin was improved by melt-crystallization methods, with 2627-fold higher than pure curcumin. The resulting Cur-NBs have a nanoscale size about 400 nm and show excellent contrast imaging performance. Curcumin drugs encapsulated into Cur-NBs could be effectively released when Cur-NBs were irradiated by LIFU at the optimized acoustic pressure, achieving 30% cumulative release rate within 6 h. Importantly, Cur-NBs combined with LIFU can open the BBB and locally deliver the curcumin into the deep-seated brain nuclei, significantly enhancing efficacy of curcumin in the Parkinson C57BL/6J mice model in comparison with only Cur-NBs and LIFU groups. CONCLUSION: In this work, we greatly improved the solubility of curcumin and developed Cur-NBs for brain delivery of curcumin against PD through combining with LIFU-mediating BBB. Cur-NBs provide a platform for these potential drugs which are difficult to cross the BBB to treat PD disease or other central nervous system (CNS) diseases.
Authors: Daniel A King; Michael J Malloy; Alayna C Roberts; Alexander Haak; Christian C Yoder; William D O'Brien Journal: J Acoust Soc Am Date: 2010-06 Impact factor: 1.840
Authors: Bart H A Lammertink; Clemens Bos; Roel Deckers; Gert Storm; Chrit T W Moonen; Jean-Michel Escoffre Journal: Front Pharmacol Date: 2015-07-10 Impact factor: 5.810