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Impact of the Drug Loading Method on the Drug Distribution and Biological Efficacy of Exosomes

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Abstract

Exosomes are biological nanovesicles that are intrinsically loaded with thousands of biomacromolecules and are principally responsible for cell-to-cell communication. Inspired by the natural payload, they have been extensively investigated as drug delivery vehicles; however, the drug distribution, whether into or onto exosomes, is still debatable. In the present work, we have tried to investigate it systemically by selecting 5-fluorouracil (5-FU) (hydrophilic) and paclitaxel (PAC) (hydrophobic), drugs with very different physicochemical characteristics, for the loading to the exosomes. Exosomes were obtained from bovine milk, and the drugs were loaded using three different methods: incubation, sonication, and triton x-100. The particle size was found to be approximately 100 nm in all the cases; however, the highest drug loading was found in the sonication method. Fluorescence spectrophotometer, EDX analysis, EDX mapping, XPS, and XRD analysis indicated the possible presence of more drugs over the surface in the case of the incubation method. Drugs loaded by the sonication method had more controlled release than simple incubation and triton x-100. The method of drug loading had an insignificant effect on the cytotoxicity while in line with our previous observation, the combination (PAC and 5-FU) exhibited synergism as evidenced by ROS assay, colony formation assay, and mitochondrial membrane potential assay.

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Data Availability

The authors declare that the data supporting the findings of this study are available within the paper and its supplementary information files. Should any raw data files be needed in another format, they are available from the corresponding author upon reasonable request.

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Acknowledgments

The authors are highly grateful to the Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU) Varanasi, for providing Infrastructure. The authors are also thankful to the Science & Engineering Research Board (SERB), Department of Science and Technology (DST), New Delhi, India, for providing the financial support required for performing this work (Grant no SRG/2019/000150).

Funding

Science & Engineering Research Board (SERB), Department of Science and Technology (DST), New Delhi, India, has funded this work (File No. SRG/2019/000150)

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Authors and Affiliations

  1. Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Dulla Naveen Kumar, Aiswarya Chaudhuri, Dinesh Kumar, Sanjay Singh & Ashish Kumar Agrawal

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  1. Dulla Naveen Kumar
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  2. Aiswarya Chaudhuri
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  3. Dinesh Kumar
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  4. Sanjay Singh
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Contributions

Dulla Naveen Kumar: conceptualization, investigation, and original draft writing; Aiswarya Chaudhuri: Methodology, review, and editing; Dinesh Kumar: Compilation and overall modification; Sanjay Singh: literature survey, review and editing; Ashish Kumar Agrawal: Conceptualization, methodology, review, editing, and supervision.

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Correspondence to Ashish Kumar Agrawal.

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Kumar, D.N., Chaudhuri, A., Kumar, D. et al. Impact of the Drug Loading Method on the Drug Distribution and Biological Efficacy of Exosomes. AAPS PharmSciTech 24, 166 (2023). https://doi.org/10.1208/s12249-023-02624-6

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