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Tumoricidal effects of etoposide incorporated into solid lipid nanoparticles after intraperitoneal administration in Dalton's lymphoma bearing mice

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Abstract

The tumoricidal effects of etoposide incorporated into lipid nanoparticles after single-dose administration were investigated in Dalton's lymphoma ascites bearing mice. Etoposide and its nanoparticle formulations were administered intraperitoneally, and the cell cycle perturbation, cytogenetic damage, cell death (apoptosis), tumor regression, and animal survival were investigated as parameters of response with time. The tumor burden of mice treated with etoposide and its nanoparticle formulations decreased significantly (P<.001) compared with the initial up to 4 to 6 days, followed by an increase at later time intervals. Of the 3 different formulations, the survival time of mice was higher when treated with etoposide-loaded tripalmitin (ETP) nanoparticles, followed by etoposide-loaded glycerol monostearate (EGMS) (27.3%) and etoposide-loaded glycerol distearate (EGDS) (27.3%) compared with free etoposide. Cell cycle analysis revealed the hypodiploid peak (sub G0/G1 cell population) as well as G2 arrest in mice treated with etoposide and its nanoparticle formulations. The frequency of dead cells treated with the nanoparticle formulations remained high even after 8 days of treatment compared with free etoposide. The mice treated with nanoparticle formulations exhibited hypodiploid peaks and reduced S phase even 8 days after treatment, whereas the free etoposide-treated mice showed decrease in apoptosis after 3 days of treatment. The apoptotic frequency in cells 17 days after treatment was in the order of ETP>EGMS>EGDS> etoposide. The experimental results indicated that among the 3 nanoparticle formulations studied, the ETP nanoparticles showed greater and prolonged apoptotic induction properties, resulting in the higher increase in survival time of tumor bearing mice.

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Authors and Affiliations

  1. Drug Delivery Research Laboratory, Center of Relevance and Excellence in NDDS, Pharmacy Department, M. S. University, G. H. Patel Building, Donor's Plaza, Fatehgunj, 390002, Baroda, Gujarat, India

    Lakkireddy Harivardhan Reddy & Rayasa Ramachandra Murthy

  2. Department of Biocybernetics, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, 110 054, Delhi, India

    Jawahar Singh Adhikari & Bilikere Srinirasa Rao Dwarakanath

  3. Department of Radiopharmaceuticals and Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, 110 054, Delhi, India

    Rakesh Kumar Sharma

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  1. Lakkireddy Harivardhan Reddy
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  2. Jawahar Singh Adhikari
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  3. Bilikere Srinirasa Rao Dwarakanath
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  4. Rakesh Kumar Sharma
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  5. Rayasa Ramachandra Murthy
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Correspondence to Lakkireddy Harivardhan Reddy.

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Published: April 14, 2006

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Reddy, L.H., Adhikari, J.S., Dwarakanath, B.S.R. et al. Tumoricidal effects of etoposide incorporated into solid lipid nanoparticles after intraperitoneal administration in Dalton's lymphoma bearing mice. AAPS J 8, 29 (2006). https://doi.org/10.1007/BF02854895

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  • DOI: https://doi.org/10.1007/BF02854895

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