| Autor: |
Koning, GA, Morselt, HWM, Kamps, JAAM, Scherphof, GL |
| Přispěvatelé: |
Groningen University Institute for Drug Exploration (GUIDE), Nanotechnology and Biophysics in Medicine (NANOBIOMED), Vascular Ageing Programme (VAP) |
| Jazyk: |
angličtina |
| Rok vydání: |
2001 |
| Předmět: |
|
| Zdroj: |
Journal of Liposome Research, 11(2-3), 195-209 |
| ISSN: |
0898-2104 |
| Popis: |
Specific targeting of drugs to for instance tumors or sites of inflammation may be achieved by means of immunoliposomes carrying site-specific antibodies on their surface. The presence of these antibodies may adversely affect the circulation kinetics of such liposomes as a result of interactions with cells of the mononuclear phagocyte system (MPS), mainly represented by macrophages in liver and spleen. The additional insertion of poly(ethylene glycol) chains on the surface of the immunoliposomes may, however, attenuate this effect. We investigated the influence of surface-coupled rat or rabbit antibodies and of PEG on the uptake of liposomes by rat Kupffer cells in culture with H-3-cholesteryloleyl ether as a metabolically stable marker. Additionally, we assessed the effects of surface-bound IgG and PEG on the intracellular processing of the liposomes by the Kupffer cells, based on a double-label assay using the H-3-cholesteryl ether as an absolute measure for liposome uptake and the hydrolysis of the degradable marker cholesteryl-C-14-oleate as relative measure of degradation. Attachment of both rat and rabbit antibodies to PEG-free liposomes caused a several-fold increase in apparent size. The uptake by Kupffer cells, however, was 3-4 fold higher for the rat than for the rabbit IgG liposomes. The presence of PEG drastically reduced the difference between these liposome types. Uptake of liposomes without antibodies amounted to only about 10% (non-PEGylated) or less (PEGylated) of that of the immunoliposomes. In contrast to the marked effects of IgG and PEG on Kupffer cell uptake, the rate of intracellular processing of the liposomes remained virtually unaffected by the presence of these substances on the liposomal surface. These observations are discussed with respect to the design of optimally formulated liposomal drug preparations, combining maximal therapeutic efficacy with minimal toxicity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
