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A Density-Changing Centrifugation Method for Efficient Separation of Free Drugs from Drug-Loaded Particulate Delivery Systems

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Abstract

Commonly used separation techniques, such as ultracentrifugation, chromatography, and membrane separation, have inherent drawbacks that limit their usage. Herein, we introduced a new separation method, density-changing centrifugation (DCC), which is based on trisodium citrate (TC) and ultracentrifugation. Paclitaxel-loaded cationic solid lipid nanoparticles (SLNs/PTX) and doxorubicin-loaded PEGylated liposomes (Lipo/Dox) were prepared as model drug delivery particulates. After optimizing TC concentration and centrifugal conditions, DCC showed superior separation efficiency and accuracy over common ultracentrifugation and ultrafiltration methods and displayed comparable or even better separation efficiency compared with size-exclusion chromatography, as demonstrated by the determination of encapsulation efficiency, Tyndall effect, transmittance, and drug recovery. DCC was also proven to minimally impact the size distribution, surface morphology, and thermal properties of the nanoparticles and liposomes, and moreover, it did not affect the determination of drug concentrations. Together, DCC has been demonstrated as a neat and effective method for the separation of free drugs from drug-loaded SLNs and liposomes, which shall be of great benefit for the development of particulate based delivery systems.

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Funding

The authors are grateful for the financial support from the National Natural Science Foundation of China (81690261).

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Authors and Affiliations

  1. Key Laboratory of Drug Targeting and Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, No 17, Section 3, Southern Remin Rd, Chengdu, 610041, China

    Lu Han, Xun Sun, Zhi-Rong Zhang & Li Deng

  2. College of Pharmacy, Southwest Minzu University, Chengdu, China

    Lu Han

  3. Chongqing YaoPharm Co., Ltd., 100 Xingguang Avenue, Renhe Town, Yubei District, Chongqing, China

    Hongyan Zhan

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  1. Lu Han
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  2. Hongyan Zhan
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  3. Xun Sun
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  4. Zhi-Rong Zhang
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  5. Li Deng
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Correspondence to Li Deng.

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Lu Han and Hongyan Zhan are co-first authors.

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Han, L., Zhan, H., Sun, X. et al. A Density-Changing Centrifugation Method for Efficient Separation of Free Drugs from Drug-Loaded Particulate Delivery Systems. AAPS J 21, 33 (2019). https://doi.org/10.1208/s12248-019-0306-1

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  • DOI: https://doi.org/10.1208/s12248-019-0306-1

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