Abstract
In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague–Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.
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Acknowledgments
Authors would like to acknowledge All India Institute of Medical Sciences, New Delhi, India, Bhopal Memorial Health Care and Research Centre, Bhopal, India, and Tata memorial hospital, Mumbai, India, for providing facilities for TEM, LDL and HDL isolation and characterization and cancer cell line studies, respectively
Author Ms. Anupriya Jain is highly indebted to University grant commission, New Delhi, India for providing financial assistance in form of Junior Research Fellowship (JRF).
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Jain, A., Jain, K., Mehra, N.K. et al. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells. J Nanopart Res 15, 2003 (2013). https://doi.org/10.1007/s11051-013-2003-9
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DOI: https://doi.org/10.1007/s11051-013-2003-9