Theranostics 2018; 8(8):2264-2277. doi:10.7150/thno.23734 This issue Cite

Research Paper

Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy

Nisi Zhang#1,2, Fei Yan#2, Xiaolong Liang1, Manxiang Wu2,3, Yuanyuan Shen4, Min Chen1, Yunxue Xu1, Guangyang Zou1, Peng Jiang2, Caiyun Tang2, Hairong Zheng2✉, Zhifei Dai1✉

1. Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.
2. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
3. Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
4. School of Biomedical Engineering, Shenzhen University, Shenzhen, 518060, China.
# These authors contributed equally to this work.

Citation:
Zhang N, Yan F, Liang X, Wu M, Shen Y, Chen M, Xu Y, Zou G, Jiang P, Tang C, Zheng H, Dai Z. Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy. Theranostics 2018; 8(8):2264-2277. doi:10.7150/thno.23734. https://www.thno.org/v08p2264.htm
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Abstract

Graphic abstract

Rationale: Treatment for Parkinson's disease (PD) is challenged by the presence of the blood-brain barrier (BBB) that significantly limits the effective drug concentration in a patient's brain for therapeutic response throughout various stages of PD. Curcumin holds the potential for α-synuclein clearance to treat PD; however, its applications are still limited due to its low bioavailability and poor permeability through the BBB in a free form.

Methods: Herein, this paper fabricated curcumin-loaded polysorbate 80-modified cerasome (CPC) nanoparticles (NPs) with a mean diameter of ~110 nm for enhancing the localized curcumin delivery into the targeted brain nuclei via effective BBB opening in combination with ultrasound-targeted microbubble destruction (UTMD).

Results: The liposomal nanohybrid cerasome exhibited superior stability towards PS 80 surfactant solubilization and longer circulation lifetime (t1/2 = 6.22 h), much longer than free curcumin (t1/2 = 0.76 h). The permeation was found to be 1.7-fold higher than that of CPC treatment only at 6 h after the systemic administration of CPC NPs. Notably, motor behaviors, dopamine (DA) level and tyrosine hydroxylase (TH) expression all returned to normal, thanks to α-synuclein (AS) removal mediated by efficient curcumin delivery to the striatum. Most importantly, the animal experiment demonstrated that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice had notably improved behavior disorder and dopamine depletion during two-week post-observation after treatment with CPC NPs (15 mg curcumin/kg) coupled with UTMD.

Conclusion: This novel CPC-UTMD formulation approach could be an effective, safe and amenable choice with higher therapeutic relevance and fewer unwanted complications than conventional chemotherapeutics delivery systems for PD treatment in the near future.

Keywords: curcumin, Parkinson's disease, blood-brain barrier, cerasome, ultrasound targeting microbubbles destruction


Citation styles

APA
Zhang, N., Yan, F., Liang, X., Wu, M., Shen, Y., Chen, M., Xu, Y., Zou, G., Jiang, P., Tang, C., Zheng, H., Dai, Z. (2018). Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy. Theranostics, 8(8), 2264-2277. https://doi.org/10.7150/thno.23734.

ACS
Zhang, N.; Yan, F.; Liang, X.; Wu, M.; Shen, Y.; Chen, M.; Xu, Y.; Zou, G.; Jiang, P.; Tang, C.; Zheng, H.; Dai, Z. Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy. Theranostics 2018, 8 (8), 2264-2277. DOI: 10.7150/thno.23734.

NLM
Zhang N, Yan F, Liang X, Wu M, Shen Y, Chen M, Xu Y, Zou G, Jiang P, Tang C, Zheng H, Dai Z. Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy. Theranostics 2018; 8(8):2264-2277. doi:10.7150/thno.23734. https://www.thno.org/v08p2264.htm

CSE
Zhang N, Yan F, Liang X, Wu M, Shen Y, Chen M, Xu Y, Zou G, Jiang P, Tang C, Zheng H, Dai Z. 2018. Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy. Theranostics. 8(8):2264-2277.

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