A Gambogic Acid-Loaded Delivery System Mediated by Ultrasound-Targeted Microbubble Destruction: A Promising Therapy Method for Malignant Cerebral Glioma

超声靶向微泡破坏介导的藤黄酸递送系统:一种有前途的恶性脑胶质瘤治疗方法

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作者:Lei Dong #, Nana Li #, Xixi Wei, Yongling Wang, Liansheng Chang, Hongwei Wu, Liujiang Song, Kang Guo, Yuqiao Chang, Yaling Yin, Min Pan, Yuanyuan Shen, Feng Wang

Background

The blood-brain barrier (BBB) inhibits the delivery of macromolecular chemotherapeutic drugs to brain tumors, leading to low utilization rates and toxic side effects to surrounding tissues and organs. Ultrasonic targeted microbubble destruction (UTMD) technology can open the BBB, leading to a new type of drug delivery system with particular utility in glioma.

Conclusion

The combination of PLGA-CMB with FUS provides an effective and biocompatible drug delivery system, and its application to the delivery of GA in a mouse glioblastoma model was successful.

Methods

GA/PLGA nanoparticles were prepared by the double emulsification method, and cationic microbubbles (CMBs) were prepared by a thin film hydration method. The GA/PLGA-CMB microbubble complex was assembled through electrostatic attractions and was characterized chemically. The anti-glioblastoma effect of GA/PLGA-CMB combined with focused ultrasound (FUS) was evaluated by biochemical and imaging assays in cultured cells and model mice.

Purpose

We have developed a new type of drug-loaded microbubble complex based on poly(lactic-co-glycolic acid) (PLGA) that targets gambogic acid (GA) to the area of brain tumors through UTMD.

Results

GA/PLGA-CMB combined with FUS demonstrated a significant inhibitory effect on glioblastoma cell lines U87 and U251 as compared with controls (P<0.05). Tumor access and imaging analyses demonstrated that administration of GA/PLGA-CMBs combined with FUS can open the BBB and target the treatment of glioblastoma in a mouse model, as compared with control groups (P<0.05).

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