Doxorubicin bound to a HPMA copolymer carrier through hydrazone bond is effective also in a cancer cell line with a limited content of lysosomes.
J Control Release
; 74(1-3): 225-32, 2001 Jul 06.
Article
en En
| MEDLINE
| ID: mdl-11489498
ABSTRACT
We have synthesized conjugates containing doxorubicin (DOX) bound to oligopeptide side chains (GlyGly or GlyPheLeuGly) of a water-soluble copolymer carrier based on poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) either through proteolytically (PK1 conjugates) [Synthetic polymeric drugs. U.S. Patent 5,037,883 (1991)] or hydrolytically cleavable bond (HC conjugates). Pharmacological efficacy of PK1 and HC conjugates was compared in vitro on murine T-cell lymphoma EL4, B-cell leukemia BCL1, B-cell lymphoma 38C13, leukemia P388 and Con A-stimulated A/Ph splenocytes and on human primary (SW480) and metastatic (SW620) colorectal cancer cell lines parent and transfected with Thy 1.2 gene [2] and on erythromyeloid leukemia cell line K 562. Inhibition of proliferation determined by 3[H]-thymidine incorporation revealed that the cytostatic effect of HC conjugates is up to two orders of magnitude higher compared to PK1 conjugates. In some cancer cell lines (SW 620/T, SW 480) the pharmacological activity of HC conjugates is in vitro comparable with the activity of the free drug. Unlike PK1 conjugates, HC conjugates with a lysosomally degradable spacer (GlyPheLeuGly) are less effective compared to HC conjugates containing lysosomally non-degradable spacer (GlyGly). Moreover, HC conjugates exert pronounced anti-proliferative activity also in erythroblastoid leukemia cell line K 562 with a limited content of lysosomes.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Doxorrubicina
/
Hidrazonas
/
Lisosomas
/
Antibióticos Antineoplásicos
/
Neoplasias
Límite:
Animals
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2001
Tipo del documento:
Article
País de afiliación:
República Checa