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Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

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Abstract

The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

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Acknowledgments

Authors are thankful to M/s Khandelwal laboratory, Mumbai, India for generously supplying Dox HCl, Indian Institute of Technology, Kanpur for carrying out SEM study. We also wants to acknowledge University Grant Comission, New Delhi for financial assistance to one author (PK).

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Authors and Affiliations

  1. Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, 470003, MP, India

    Parul Kharya, Ashish Jain, Arvind Gulbake, Satish Shilpi, Ankit Jain, Pooja Hurkat & Sanjay K. Jain

  2. Division of Molecular Medicine, Bose Institute, Kolkata, 700054, India

    Subrata Majumdar

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  1. Parul Kharya
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  2. Ashish Jain
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  3. Arvind Gulbake
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  4. Satish Shilpi
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  5. Ankit Jain
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  6. Pooja Hurkat
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  7. Subrata Majumdar
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  8. Sanjay K. Jain
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Correspondence to Sanjay K. Jain.

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Kharya, P., Jain, A., Gulbake, A. et al. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting. J Nanopart Res 15, 2022 (2013). https://doi.org/10.1007/s11051-013-2022-6

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  • DOI: https://doi.org/10.1007/s11051-013-2022-6

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