Liposomal delivery of doxorubicin to hepatocytes in vivo by targeting heparan sulfate
| Autor: | Kenneth J. Longmuir, Sherry M. Haynes, Richard T. Robertson, Natasha Kasabwalla, Janie Baratta |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Chemistry
Pharmaceutical Drug Compounding Active Transport Cell Nucleus Protozoan Proteins Pharmaceutical Science Pharmacology Article Glycosaminoglycan Mice chemistry.chemical_compound Drug Stability In vivo medicine Animals Tissue Distribution Doxorubicin Drug Carriers Mice Inbred BALB C Liposome Antibiotics Antineoplastic Chemistry Liver cell Heparan sulfate Peptide Fragments Spectrometry Fluorescence medicine.anatomical_structure Microscopy Fluorescence Hepatocyte Injections Intravenous Liposomes Hepatocytes Nanoparticles Female Heparitin Sulfate Drug carrier medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 382:222-233 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2009.07.030 |
| Popis: | Previous work demonstrated that liposomes, containing an amino acid sequence that binds to hepatic heparan sulfate glycosaminoglycan, show effective targeting to liver hepatocytes. These liposomes were tested to determine whether they can deliver doxorubicin selectively to liver and hepatocytes in vivo. Fluid-phase liposomes contained a lipid-anchored 19-amino acid glycosaminoglycan targeting peptide. Liposomes were loaded with doxorubicin and were non-leaky in the presence of serum. After intravenous administration to mice, organs were harvested and the doxorubicin content extracted and measured by fluorescence intensity and by fluorescence microscopy. The liposomal doxorubicin was recovered almost entirely from liver, with only trace amounts detectable in heart, lung, and kidney. Fluorescence microscopy demonstrated doxorubicin preferentially in hepatocytes, also in non-parenchymal cells of the liver, but not in cells of heart, lung or kidney. The doxorubicin was localized within liver cell nuclei within five minutes after intravenous injection. These studies demonstrated that liposomal doxorubicin can be effectively delivered to hepatocytes by targeting the heparan sulfate glycosaminoglycan of liver tissue. With the composition described here, the doxorubicin was rapidly released from the liposomes without the need for an externally supplied stimulus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect