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Volume 18
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10.3390/ph18081169
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Daptomycin-Loaded Nano-Drug Delivery System Based on Biomimetic Cell Membrane Coating Technology: Preparation, Characterization, and Evaluation

by
Yuqin Zhou
1,2,
Shihan Du
1,
Kailun He
2,
Beilei Zhou
2,
Zixuan Chen
3,
Cheng Zheng
2,
Minghao Zhou
2,
Jue Li
2,
Yue Chen
2,
Hu Zhang
4,
Hong Yuan
5,
Yinghong Li
2,5,*,
Yan Chen
6 and
Fuqiang Hu
5,*
1
School of Pharmacy, China Pharmaceutical University, No. 639, Longmian Avenue, Nanjing 211198, China
2
NMPA Key Laboratory for Testing and Warning of Pharmaceutical Microbiology, Zhejiang Key Laboratory of Biopharmaceutical Contact Materials, Zhejiang Institute for Food and Drug Control, No. 325 Pingle Street, Binjiang District, Hangzhou 310052, China
3
School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou 311399, China
4
Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, No. 198 Shiqiao Road, Hangzhou 310021, China
5
College of Pharmaceutical Science, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou 310058, China
6
Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(8), 1169; https://doi.org/10.3390/ph18081169
Submission received: 30 June 2025 / Revised: 31 July 2025 / Accepted: 2 August 2025 / Published: 6 August 2025
(This article belongs to the Section Pharmaceutical Technology)
Versions Notes

Abstract

Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 ± 13.72 nm, with zeta potential +11.90 ± 1.90 mV, and encapsulation efficiency 70.43 ± 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP.
Keywords: daptomycin; M1-type macrophage membrane; Staphylococcus aureus; drug-resistance; zebrafish daptomycin; M1-type macrophage membrane; Staphylococcus aureus; drug-resistance; zebrafish

Share and Cite

MDPI and ACS Style

Zhou, Y.; Du, S.; He, K.; Zhou, B.; Chen, Z.; Zheng, C.; Zhou, M.; Li, J.; Chen, Y.; Zhang, H.; et al. Daptomycin-Loaded Nano-Drug Delivery System Based on Biomimetic Cell Membrane Coating Technology: Preparation, Characterization, and Evaluation. Pharmaceuticals 2025, 18, 1169. https://doi.org/10.3390/ph18081169

AMA Style

Zhou Y, Du S, He K, Zhou B, Chen Z, Zheng C, Zhou M, Li J, Chen Y, Zhang H, et al. Daptomycin-Loaded Nano-Drug Delivery System Based on Biomimetic Cell Membrane Coating Technology: Preparation, Characterization, and Evaluation. Pharmaceuticals. 2025; 18(8):1169. https://doi.org/10.3390/ph18081169

Chicago/Turabian Style

Zhou, Yuqin, Shihan Du, Kailun He, Beilei Zhou, Zixuan Chen, Cheng Zheng, Minghao Zhou, Jue Li, Yue Chen, Hu Zhang, and et al. 2025. "Daptomycin-Loaded Nano-Drug Delivery System Based on Biomimetic Cell Membrane Coating Technology: Preparation, Characterization, and Evaluation" Pharmaceuticals 18, no. 8: 1169. https://doi.org/10.3390/ph18081169

APA Style

Zhou, Y., Du, S., He, K., Zhou, B., Chen, Z., Zheng, C., Zhou, M., Li, J., Chen, Y., Zhang, H., Yuan, H., Li, Y., Chen, Y., & Hu, F. (2025). Daptomycin-Loaded Nano-Drug Delivery System Based on Biomimetic Cell Membrane Coating Technology: Preparation, Characterization, and Evaluation. Pharmaceuticals, 18(8), 1169. https://doi.org/10.3390/ph18081169

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