Journal article
Characterization, toxicity and therapeutic efficacy of adrïamycin encapsulated in liposomes
European journal of cancer & clinical oncology, Vol.18(2), pp.167,171-169,176
1982
DOI: 10.1016/0277-5379(82)90060-8
PMID: 7201392
Abstract
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 LD
50 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
μm pore size) and purified by exhaustive dialysis. This preparation had a mean vesicle diameter of 0.24
μm 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 LD
50 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 vitro, 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. × time value for 48
hr) following encapsulated drug administration. Encapsulating adriamycin in liposomes did not alter its therapeutic effect against L1210 leukemic cells
in vivo.
Details
- Title: Subtitle
- Characterization, toxicity and therapeutic efficacy of adrïamycin encapsulated in liposomes
- Creators
- F. Olson - Roswell Park Cancer InstituteE. Mayhew - Roswell Park Cancer InstituteD. Maslow - Roswell Park Cancer InstituteY. Rustum - Roswell Park Cancer InstituteF. Szoka - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- European journal of cancer & clinical oncology, Vol.18(2), pp.167,171-169,176
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/0277-5379(82)90060-8
- PMID
- 7201392
- ISSN
- 0277-5379
- Language
- English
- Date published
- 1982
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359942802771
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