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An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles
BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752169/ https://www.ncbi.nlm.nih.gov/pubmed/19806207 http://dx.doi.org/10.1371/journal.pone.0007240 |
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author | Krishna, Athuluri Divakar Sai Mandraju, Raj Kumar Kishore, Golla Kondapi, Anand Kumar |
author_facet | Krishna, Athuluri Divakar Sai Mandraju, Raj Kumar Kishore, Golla Kondapi, Anand Kumar |
author_sort | Krishna, Athuluri Divakar Sai |
collection | PubMed |
description | BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano) have diameters of 25–50 ηm, which increase to 60–80 ηm upon direct loading of drug (direct-nano), and showed further increase in dimension (75–95 ηm) in conjugated nanoparticles (conj-nano). The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a) localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus) (b) pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c) the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in regression of hepatocellular carcinoma with negligible toxicity to kidney and liver. CONCLUSIONS: The present study thus demonstrates that the direct-nano is highly efficacious in delivery of drug in a target specific manner with lower toxicity to heart, liver and kidney. |
format | Text |
id | pubmed-2752169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27521692009-10-06 An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles Krishna, Athuluri Divakar Sai Mandraju, Raj Kumar Kishore, Golla Kondapi, Anand Kumar PLoS One Research Article BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano) have diameters of 25–50 ηm, which increase to 60–80 ηm upon direct loading of drug (direct-nano), and showed further increase in dimension (75–95 ηm) in conjugated nanoparticles (conj-nano). The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a) localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus) (b) pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c) the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in regression of hepatocellular carcinoma with negligible toxicity to kidney and liver. CONCLUSIONS: The present study thus demonstrates that the direct-nano is highly efficacious in delivery of drug in a target specific manner with lower toxicity to heart, liver and kidney. Public Library of Science 2009-10-02 /pmc/articles/PMC2752169/ /pubmed/19806207 http://dx.doi.org/10.1371/journal.pone.0007240 Text en Krishna et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Krishna, Athuluri Divakar Sai Mandraju, Raj Kumar Kishore, Golla Kondapi, Anand Kumar An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles |
title | An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles |
title_full | An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles |
title_fullStr | An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles |
title_full_unstemmed | An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles |
title_short | An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles |
title_sort | efficient targeted drug delivery through apotransferrin loaded nanoparticles |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752169/ https://www.ncbi.nlm.nih.gov/pubmed/19806207 http://dx.doi.org/10.1371/journal.pone.0007240 |
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