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Inducing Controlled Release and Increased Tumor-Targeted Delivery of Chlorambucil via Albumin/Liposome Hybrid Nanoparticles

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Abstract

Liposomes possess good biocompatibility and excellent tumor-targeting capacity. However, the rapid premature release of lipophilic drugs from the lipid bilayer of liposomes has negative effect on the tumor-targeted drug delivery of liposomes. In this study, a lipophilic antitumor drug—chlorambucil (CHL)—was encapsulated into the aqueous interior of liposomes with the aid of albumin to obtain the CHL-loaded liposomes/albumin hybrid nanoparticles (CHL-Hybrids). The in vitro accumulative release rate of CHL from CHL-Hybrids was less than 50% within 48 h, while the accumulative CHL release was more than 80% for CHL-loaded liposomes (CHL-Lip). After intravenous injection into rats, the half-life (t 1/2β = 5.68 h) and maximum blood concentration (C max = 4.58 μg/mL) of CHL-Hybrids were respectively 1.1 times and 3.5 times higher than that of CHL-Lip. In addition, CHL-Hybrids had better tumor-targeting capacity for it significantly increased the drug accumulation in B16F10 tumors, which contributed to the significantly control of tumor growth compared with CHL-Lip. Furthermore, CHL-Hybrid-treated B16F10 melanoma-bearing mice displayed the longest median survival time of 30.0 days among all the treated groups. Our results illustrated that the proposed hybrids drug delivery system would be a promising strategy to maintain the controlled release of lipophilic antitumor drugs from liposomes and simultaneously facilitate the tumor-targeted drug delivery.

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Acknowledgements

We would like to thank for the financial supports of the National Natural Science Foundation of China (No. 81603045) and the Hainan International Cooperation Agreement (No. KJHZ2014-03).

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  1. Quan Zhang and Li Zhang contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Chengdu Medical College, No. 783, Xindu Avenue, Chengdu, Sichuan, 610500, China

    Quan Zhang, Zemin Li, Xingliang Xie, Xiurong Gao & Xiaohong Xu

  2. School of Pharmacy, Hainan Medical College, Haikou, 570000, China

    Li Zhang

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  1. Quan Zhang
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  2. Li Zhang
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  3. Zemin Li
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Correspondence to Quan Zhang or Xiaohong Xu.

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All animal experiments were performed in compliance with the Guidelines of the Care and Use of Laboratory Animals and approved by the Experiment Animal Administrative Committee of Chengdu Medical College.

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Zhang, Q., Zhang, L., Li, Z. et al. Inducing Controlled Release and Increased Tumor-Targeted Delivery of Chlorambucil via Albumin/Liposome Hybrid Nanoparticles. AAPS PharmSciTech 18, 2977–2986 (2017). https://doi.org/10.1208/s12249-017-0782-5

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