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Formulation and Physicochemical and Biological Characterization of Etoposide-Loaded Submicron Emulsions with Biosurfactant of Sophorolipids

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Abstract

Etoposide (ETO), a traditional anticancer chemotherapeutic agent, is commercialized in oral soft gelatin capsules and non-aqueous parenteral solutions form. Novel formulation application and new excipients exploration are needed to improve the water-solubility and comfort of the drug administration. In the present study, novel etoposide-loaded submicron emulsions (ESE) with the biosurfactants of acidic sophorolipid (ASL) and lactonic sophorolipid (LSL) instead of the chemical surfactant of Tween-80 were prepared and characterized. Firstly, parameters of medium-chain triglyceride: long-chain triglyceride (MCT:LCT), lecithin concentration, homogenization pressure and cycle, and type and concentration of surfactants were investigated to optimize the formation of ESEs. Then the physicochemical properties, antitumor activity, stability, and security of ESEs were compared. The results showed that ASL performed the best properties and activities than Tween-80 and LSL in ESE formation. ASL-ESE showed higher drug loading capacity, slower release rate, and significantly increased antitumor activity against ovarian cancer cell line A2780 via apoptosis than Tween-ESE and commercial ETO injection. Besides, both ASL-ESE and Tween-ESE caused no hemolysis, and the safe dose of ASL was 2.14-fold that of Tween-80 in the hemolysis test, making ASL more reliable for drug delivery applications. Furthermore, ASL-ESE exhibited equivalent long-term and autoclaving stability to Tween-ESE. These results thus suggested the excellent competences of ASL in ESE formation, efficacy enhancement, and safety improvement.

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Abbreviations

ETO:

Etoposide

SE:

Submicron emulsion

ESE:

Etoposide-loaded submicron emulsions

SLs:

Sophorolipids

ASL:

Acidic sophorolipid

LSL:

Lactonic sophorolipid

PDI:

Polydispersity index

RLC:

Relative loading capacity

EE:

Entrapment efficiency

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Funding

We wish to acknowledge the financial support provided by the Fundamental Research Funds for the Central Universities of China [JZ2021HGTB0114], the National Natural Science Foundation of China [31400049] and the Key Research and development program of Anhui Province [202004a06020041].

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Authors and Affiliations

  1. School of Food and Biological Engineering, Hefei University of Technology, Tunxi Road 193, Hefei, 230009, China

    Xiaojing Ma, Tong Wang, Zequan Yu, Junqian Shao, Huixia Zhu & Risheng Yao

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 02215, USA

    Xiaojing Ma & Jun Chu

  3. Key Laboratory of Xin’An Medicine, Ministry of Education, Centre of Scientific Research Technology, Anhui University of Chinese Medicine, Hefei, 230038, China

    Jun Chu

Authors
  1. Xiaojing Ma
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  2. Tong Wang
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  3. Zequan Yu
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  5. Jun Chu
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  6. Huixia Zhu
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Contributions

Xiaojing Ma: methodology, supervision, writing-reviewing and editing, funding acquisition. Tong Wang: validation, formal analysis, investigation. Junqian Shao: validation, investigation and writing-original draft. Zequan Yu: fix the article format and check the article errors. Jun Chu: resources. Huixia Zhu: resources. Risheng Yao: conceptualization.

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Correspondence to Xiaojing Ma.

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Highlights

• Sophorolipids and Tween-80-based etoposide submicron emulsions (ESEs) are prepared.

• Acidic SL (ASL) is more beneficial than Tween-80 in high-quality ESE preparation.

• ASL-ESE exhibits greater antitumor efficacy, stability, and safety than Tween-ESE.

• ASL performs the competences in ESE formation and drug delivery system exploration.

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Ma, X., Wang, T., Yu, Z. et al. Formulation and Physicochemical and Biological Characterization of Etoposide-Loaded Submicron Emulsions with Biosurfactant of Sophorolipids. AAPS PharmSciTech 23, 181 (2022). https://doi.org/10.1208/s12249-022-02329-2

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