Electrospun poly (L-lactic acid)/gelatine membranes loaded with doxorubicin for effective suppression of glioblastoma cell growth in vitro and in vivo

Author:

Liu Boxun1,Jin Zhizhong2,Chen Haiyan1,Liang Lun3,Li Yao1,Wang Guo4,Zhang Jing5,Xu Tao167

Affiliation:

1. Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518055, China

2. Department of Neurosurgery, the First Hospital of China Medical University, Shenyang 110122, China

3. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China

4. East China Institute of Digital Medical Engineering, Shangrao 334000, China

5. Medprin Regenerative Medical Technologies Co., Ltd, Guangzhou 510663, China

6. Key Laboratory for Advanced Materials Processing Technology, Ministry of Education; Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China

7. Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing; Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China

Abstract

Abstract Electrospun membranes are attracting interest as a drug delivery system because of their material composition flexibility and versatile drug loading. In this study, the electrospun membrane was loaded with doxorubicin (DOX) via electrostatic adsorption for long-term drug delivery. DOX loading process was optimized by varying temperature, time, drug concentration, pH and ionic strength of solutions. The loading process did not impair the structural properties of the membrane. Next, we investigated the drug release kinetics using spectroscopic techniques. The composite membranes released 22% of the adsorbed DOX over the first 48 h, followed by a slower and sustained release over 4 weeks. The DOX release was sensitive to acidic solutions that the release rate at pH 6.0 was 1.27 times as that at pH 7.4. The DOX-loaded membranes were found to be cytotoxic to U-87 MG cells in vitro that decreased the cell viability from 82.92% to 25.49% from 24 to 72 h of co-incubation. These membranes showed strong efficacy in suppressing tumour growth in vivo in glioblastoma-bearing mice that decreased the tumour volume by 77.33% compared with blank membrane-treated group on Day 20. In conclusion, we have developed an effective approach to load DOX within a clinically approved poly (L-lactic acid)/gelatine membrane for local and long-term delivery of DOX for the treatment of glioblastoma.

Funder

National Natural Science Foundation of China

China postdoctoral Science Foundation

Publisher

Oxford University Press (OUP)

Subject

Biomaterials

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