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Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery

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Abstract

Nanosized lipid carriers (NLC) can improve the limited drug-loading (DL) capacity and drug expulsion during storage, and adjust the drug release profile of solid lipid nanoparticles (SLN). In this study, Paclitaxel (PTX)-loaded NLC were prepared by solvent diffusion method using monostearin as solid lipid and oleic acid (OA) as liquid lipid matrix. The blank NLC with different OA content (the size range was from 89.5 ± 7.4 to 160.2 ± 34.6 nm) showed smaller size than the blank SLN (the size was 272.7 ± 43.6 nm), while the PTX-loaded NLC (the size range was from 481.3 ± 29.8 to 561.7 ± 38.3 nm) showed little bigger size, higher DL capacity, and faster drug in vitro release rate comparing with SLN (the size was 437.3 ± 68.2 nm). The 50 % cellular growth inhibitions (IC50) of PTX-loaded NLC with 0, 5, 10, and 20 wt % OA were 0.92 ± 0.06, 0.69 ± 0.04, 0.25 ± 0.02, and 0.12 ± 0.02 µg mL−1, respectively, while the IC50 of TaxolTM was 1.72 ± 0.09 µg mL−1. For analyzing cellular drug effect, cellular uptakes of fluorescent NLC and intracellular drug concentration were investigated. As the incorporation of OA into solid lipid matrix could accelerate both the cellular uptake and the PTX delivery, loaded by NLC, the cytotoxicity of PTX could be enhanced, and further enhanced by increasing OA content in NLC.

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Acknowledgments

We appreciate the financial support from the National Nature Science Foundation of China (No. 81200428, No. 81402862 and No. 81400958), General research project of Zhejiang province health department (2013KYA073), and the National Construction Project of Key Clinical Specialties(Clinical pharmacy).

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Authors and Affiliations

  1. Department of Pharmacy, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China

    Jing Miao, Xingguo Zhang, Qian Li & Yuefeng Rao

  2. College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People’s Republic of China

    Yongzhong Du, Hong Yuan & Fuqiang Hu

  3. Women’s Hospital, College of Medicine, Zhejiang University, 2 Xueshi Road, Hangzhou, 310006, People’s Republic of China

    Mengdan Zhao

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  1. Jing Miao
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  2. Yongzhong Du
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  3. Hong Yuan
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  4. Xingguo Zhang
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  5. Qian Li
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  6. Yuefeng Rao
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  7. Mengdan Zhao
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  8. Fuqiang Hu
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Correspondence to Jing Miao or Fuqiang Hu.

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Miao, J., Du, Y., Yuan, H. et al. Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery. J Nanopart Res 17, 10 (2015). https://doi.org/10.1007/s11051-014-2852-x

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  • DOI: https://doi.org/10.1007/s11051-014-2852-x

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