Characterization, toxicity and therapeutic efficacy of adrïamycin encapsulated in liposomes
| Autor: | Fred C. Olson, David E. Maslow, Eric Mayhew, Francis C. Szoka, Youcef M. Rustum |
|---|---|
| Rok vydání: | 1982 |
| Předmět: |
Drug
media_common.quotation_subject Pharmacology Median lethal dose Lethal Dose 50 Mice In vivo Animals Leukemia L1210 Cells Cultured media_common Liposome Dose-Response Relationship Drug Chemistry Myocardium Vesicle Heart In vitro Mice Inbred C57BL Dose–response relationship Oncology Biochemistry Doxorubicin Mice Inbred DBA Liposomes Toxicity Female Chickens |
| Zdroj: | European Journal of Cancer and Clinical Oncology. 18:167-176 |
| ISSN: | 0277-5379 |
| DOI: | 10.1016/0277-5379(82)90060-8 |
| Popis: | The inherent toxicities of drug-free liposomes were compared. Positively charged liposomes were more toxic in vitro (chick heart cells) and in vivo (5-fold reduction in LD50 in mice) than neutral or negatively charged liposomes. Based on these findings, adriamycin was encapsulated in negatively charged liposomes (PG: PC: Chol--1:4:5), sequentially extruded through polycarbonate membranes (to 0.2 micrometer pore size) and purified by exhaustive dialysis. This preparation had a mean vesicle diameter of 0.24 micrometer and was stable in serum (24 hr drug retention of 85%). As compared with free drug, liposome-encapsulated adriamycin was less toxic in vitro to chick heart cells. In mice, adriamycin displayed short- (4-14 day) and long- (45-70 day) term toxicity. Encapsulating adriamycin increased both short- (20-50 mg/kg) and long- (10-15 mg/kg to 25-30 mg/kg) term LD50 levels. As compared with free drug, administering encapsulated adriamycin in vivo reduced the incidence of cardiac histopathologic lesions at 20 and 40 mg/kg. Compared in vivo, plasma levels of liposome-encapsulated adriamycin were 2/3-fold higher than free drug up to 24 hr post drug administration. Cardiac uptake of adriamycin was reduced 2-fold (conc x time value for 48 h) following encapsulated drug administration. Encapsulating adriamycin in liposomes did not alter its therapeutic effect against L1210 leukemic cells in vivo. |
| Databáze: | OpenAIRE |
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