Fate of cationic liposomes and their complex with oligonucleotive in vivo
| Autor: | Iwona Wala, Collins David S, Stephen Kaufman, Catherine L. Farrell, David C. Litzinger, Jeffrey M. Brown, Gwyneth Y. han |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Biodistribution
government.form_of_government Oligonucleotides Oligonucleotive Antisense therapy Biophysics Spleen Vacuole Biochemistry Mice In vivo Cations medicine Animals Cationic liposome Microscopy Immunoelectron Lung Skin Liposome Chemistry Phosphatidylethanolamines Indium Radioisotopes Cell Biology Pentetic Acid Immunohistochemistry In vitro Blood Cholesterol medicine.anatomical_structure Liver Organ Specificity Liposomes Vacuoles government Lysosomes |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1281:139-149 |
| ISSN: | 0005-2736 |
| DOI: | 10.1016/0005-2736(95)00268-5 |
| Popis: | The present studies describe the biodistribution of cationic liposomes and cationic liposome/oligonucleotide complex following intravenous injection into mice via the tail vein. (111)In-diethylenetriaminepentaacetic acid stearylamide ((111)In-DTPA-SA) was used as a lipid-phase radiolabel. Inclusion of up to 5 mol% DTPA-SA in liposomes composed of 3beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-Chol) and dioleoylphosphatidylethanolamine (DOPE) did not influence liposome formation or size, nor the binding/uptake or fusion of the cationic liposomes with CHO cells in vitro. Moreover, nuclear delivery of oligonucleotide to CHO cells was unaffected by the probe. The biodistribution of liposomes with increasing concentration of DC-Chol (1:4-4:1, DC-Chol/DOPE, mol/mol) at 24 h post-injection revealed no dependence on lipid composition. Uptake was primarily by liver, and accumulation in spleen and skin was also observed. Comparatively little accumulation occurred in lung. Clearance of injected liposomes by liver was very rapid (approximately 84.5% of the injected dose by 7.5 h post-injection). Liposome uptake by liver and spleen were equally efficient in the dose range of 3.33 to 33.33 mg/kg body weight, yet possible saturation of liver uptake at a dose of 66.80 mg/kg may have allowed for increased spleen accumulation. Preincubation of cationic liposomes with phosphorothioate oligonucleotide induced a dramatic yet transient accumulation of the lipid in lung which gradually redistributed to liver. Similar results were observed when monitoring iodinated oligonucleotide in the complex. Immuno-histochemical studies revealed large aggregates of oligonucleotide within pulmonary capillaries at 15 min post-injection, suggesting the early accumulation in lung was due to embolism. Immuno-histochemical studies further revealed labeled oligonucleotide to be localized primarily to Kupffer cells at 24 h post-injection. Immuno-electron microscopy revealed localization of oligonucleotide primarily to the lumen of pulmonary capillaries at 15 min post-injection. Immuno-electron microscopy revealed localization of oligonucleotide primarily to the lumen of pulmonary capillaries at 15 min post-injection, and to phagocytic vacuoles of Kupffer cells at 24 h post-injection. By these methods, nuclear delivery of oligonucleotide in vivo was not observed. Increasing concentration of mouse serum inhibited cellular binding/uptake of cationic liposomes in vitro, without or with complexed oligonucleotide. We therefore postulate that interaction with plasma components, including opsonin(s), inhibits cellular uptake of the injected liposomes as well as the liposome/oligonucleotide complex, and mediates rapid uptake by Kupffer cells of the liver. These results are relevant to the design of cationic liposomes for efficient delivery of nucleic acid in vivo. |
| Databáze: | OpenAIRE |
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