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Promoting Antitumor Activities of Hydroxycamptothecin by Encapsulation into Acid-Labile Nanoparticles Using Electrospraying

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ABSTRACT

Purpose

Acid-labile nanoparticles are proposed to enhance the tumor targeting and anti-tumor therapy of hydroxycamptothecin (HCPT) in response to the acidic microenvironment within cells and tumor tissues.

Methods

HCPT was entrapped into matrix polymers containing acid-labile segments and galactose moieties (PGBELA) through an electrospraying technique. The antitumor activities of HCPT-loaded nanoparticles were evaluated both on HepG2 cells and after intravenous injection into H22 tumor-bearing mice.

Results

The electrosprayed nanoparticles were obtained with enhanced loading efficiency and extended release of HCPT compared with other nanoparticle preparation methods. The acid-lability and targeting capability of PGBELA nanoparticles resulted in a 5 times higher inhibitory activity after incubation in pH 6.8 media compared to that of pH 7.4. Animal studies indicated that both the blood circulation time and tumor distribution of PGBELA nanoparticles were significantly increased. HCPT/PGBELA nanoparticles indicated a superior in vivo antitumor activity and fewer side effects than other treatments on the basis of tumor growth, animal survival rate, tissue necrosis and cell apoptosis evaluation.

Conclusion

Biodegradable PGBELA nanoparticles are capable of achieving site-specific drug delivery by active targeting and triggered release by acidic pH both in tumor tissues and after internalization within tumor cells, thereby providing a novel strategy for cancer treatment.

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ACKNOWLEDGMENTS AND DISCLOSURES

Xiaoming Luo and Guoqing Jia contributed equally to the work. The authors thank Dr. Manfred F. Maitz from Max Bergmann Center of Biomaterials Dresden, Leibniz Institute of Polymer Research Dresden for his useful comments and language editing. This work was supported by National Natural Science Foundation of China (51073130 and 21274117), Specialized Research Fund for the Doctoral Program of Higher Education (20050613025 and 20120184110004), and Scientific and Technical Supporting Programs of Sichuan Province (2013SZ0084).

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Authors and Affiliations

  1. Key Laboratory of Advanced Technologies of Materials Ministry of Education of China School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, People’s Republic of China

    Xiaoming Luo, Guoqing Jia, Chaoyu Liu, Guannan Wu & Xiaohong Li

  2. Department of Biomedical Science, Chengdu Medical College, Chengdu, 610083, People’s Republic of China

    Haixing Song

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  1. Xiaoming Luo
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  2. Guoqing Jia
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Corresponding author

Correspondence to Xiaohong Li.

Electronic Supplementary Material

The orthogonal experimental design to quantitatively evaluate and statistically analyze the effects of electrospraying parameters on the nanoparticle properties was included in the supplementary material.

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Luo, X., Jia, G., Song, H. et al. Promoting Antitumor Activities of Hydroxycamptothecin by Encapsulation into Acid-Labile Nanoparticles Using Electrospraying. Pharm Res 31, 46–59 (2014). https://doi.org/10.1007/s11095-013-1130-4

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  • DOI: https://doi.org/10.1007/s11095-013-1130-4

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