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Construction and Evaluation of Traceable rhES-QDs-M-MS Protein Delivery System: Sustained-Release Properties, Targeted Effect, and Antitumor Activity

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Abstract

Recombinant human endostatin (rhES) is a protein drug with poor stability and short in vivo circulation time. The present study was therefore aimed at developing sustained-release lung targeted microspheres drug delivery system and evaluating its targeting efficiency using in vivo imaging techniques with quantum dots (QDs) as the imaging material. The oil-soluble QDs were coated with amphiphilic polymers to obtain a polymer-quantum dots micelle (QDs-M) with the potential to stably disperse in water. The rhES and QDs-M were combined using covalent bonds. The rhES-QDs-M microspheres (rhES-QDs-M-MS) were prepared using electrostatic spray technology and also evaluated via in vivo imaging techniques. The pharmacodynamics was further studied in mice. The rhES-QDs-M-MS (4–8 μm) were stable in an aqueous medium with good optical properties. The in vitro studies showed that the rhES-QDs-M-MS had sustained release which was maintained for at least 15 days (cumulative release >80%) without any burst release. The rhES-QDs-M-MS had a very high safety profile and also effectively inhibited the in vitro proliferation of human umbilical vein endothelial cells by about 70%. The pharmacokinetic results showed that the rhES could still be detected at 72 h in the experimental group which meant that the rhES-QDs-M-MS had a significant sustained-release effect. The rhES-QDs-M-MS had a better lung targeting effect and higher antitumor activity compared with the rhES. The traceable rhES-QDs-M-MS served as a promising drug delivery system for the poorly stable rhES proteins and significantly increased its lung-targeted effect, sustained-release properties, and antitumor activities.

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Funding

This work was supported by Wuyi University Scientific Research Project (No. 2017RC28), Jurong Science&Technology Program (No. YF202004), 2020 Haimen Dongzhou Talent Project, 2021 Zhenjiang sixth “169 project” scientific research project, 2021 Jurong Social Development Science&Technology Program (No. ZA42109).

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Authors and Affiliations

  1. School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529000, People’s Republic of China

    Xiaowen Wu, Yi Du & Hongfei Liu

  2. College of Pharmacy, Jiangsu University, Zhenjiang, 212013, People’s Republic of China

    Yi Zou, Kunyu Du, Caleb Kesse Firempong & Hongfei Liu

  3. Jiangsu Sunan Pharmaceutical Industrial Co., LTD, Zhenjiang, 212400, People’s Republic of China

    Yang Yu & Hongfei Liu

  4. Department of Pharmaceutics, College of Pharmacy, Shenyang pharmaceutical university, Shenyang, 110016, People’s Republic of China

    Haibing He & Changshan Sun

  5. Jiangsu Haizhihong Biomedical Co., Ltd, Nantong, 226001, People’s Republic of China

    Haibing He

  6. Shanghai Meiyou Pharmaceutical Co., Ltd, Shanghai, 201400, People’s Republic of China

    Changshan Sun

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  1. Xiaowen Wu
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Wu, X., Zou, Y., Du, K. et al. Construction and Evaluation of Traceable rhES-QDs-M-MS Protein Delivery System: Sustained-Release Properties, Targeted Effect, and Antitumor Activity. AAPS PharmSciTech 23, 207 (2022). https://doi.org/10.1208/s12249-022-02326-5

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