Liposomes incorporating a Plasmodium amino acid sequence target heparan sulfate binding sites in liver
| Autor: | Kenneth J. Longmuir, Sherry M. Haynes, Janie Baratta, Richard T. Robertson |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Plasmodium
Molecular Sequence Data Protozoan Proteins Pharmaceutical Science Biology chemistry.chemical_compound Mice medicine Animals Heparanase Chondroitin sulfate Amino Acid Sequence Liposome Heparinase Drug Carriers Mice Inbred BALB C Binding Sites Heparan sulfate Heparin Molecular biology Immunohistochemistry medicine.anatomical_structure chemistry Biochemistry Liver Hepatocyte Liposomes Heparan sulfate binding Female Heparitin Sulfate medicine.drug |
| Zdroj: | Journal of pharmaceutical sciences. 97(8) |
| ISSN: | 1520-6017 |
| Popis: | Previous studies demonstrated that intravenously administered liposomes, incorporating a peptide from the Plasmodium circumsporozoite protein, accumulate rapidly and selectively in mouse liver. The present investigation was designed to determine the molecular components in liver responsible for liposome targeting. Studies of liver tissue slices demonstrated that immunoreactivity for heparan sulfate proteoglycan (HSPG), but not other tested proteoglycans, was distributed along sinusoidal borders of liver; this immunoreactivity appeared associated with nonparenchymal cells of the sinusoids and with the basolateral portion of hepatocytes. Peptide-containing liposomes bound to liver tissue in a pattern similar to the distribution of heparan sulfate immunoreactivity, either after intravenous injection of liposomes in vivo or after incubation of liposomes with liver slices in vitro. Control liposomes, without the peptide, displayed very light binding without a pattern. Pretreatment of liver slices with heparinase, but not chondroitinase or hyaluronidase, eliminated peptide-containing liposome binding, but did not affect binding of control liposomes. Coincubation of peptide-containing liposomes with heparin, but not with other glycosaminoglycans, markedly inhibited liposome binding to liver slices. N-desulfated and O-desulfated heparins individually were less effective inhibitors of liposome binding than was heparin. These results indicate that liposomes containing a peptide from Plasmodium target liver tissue by binding to HSPGs in the extracellular matrix. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3257–3273, 2008 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text