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Titolo:
Camptothecin delivery systems: the utility of amino acid spacers for the conjugation of camptothecin with polyethylene glycol to create prodrugs
Autore:
Conover, CD; Greenwald, RB; Pendri, A; Shum, KL;
Indirizzi:
Enzon Inc, Res & Dev, Piscataway, NJ 08854 USA Enzon Inc Piscataway NJ USA 08854 nc, Res & Dev, Piscataway, NJ 08854 USA
Titolo Testata:
ANTI-CANCER DRUG DESIGN
fascicolo: 6, volume: 14, anno: 1999,
pagine: 499 - 506
SICI:
0266-9536(199912)14:6<499:CDSTUO>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTITUMOR-ACTIVITY; DRUG-DELIVERY; TUMOR ACCUMULATION; POLY(ETHYLENE GLYCOL); PEPTIDE TRANSPORTER; ANTICANCER AGENTS; ESTER PRODRUGS; DERIVATIVES; DESIGN; PHARMACOLOGY;
Keywords:
camptothecin; mouse; polyethylene glycol; prodrug; xenograft;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Conover, CD Enzon Inc, Res & Dev, 20 Kingsbridge Rd, Piscataway, NJ 08854 USA Enzon Inc 20 Kingsbridge Rd Piscataway NJ USA 08854 08854 USA
Citazione:
C.D. Conover et al., "Camptothecin delivery systems: the utility of amino acid spacers for the conjugation of camptothecin with polyethylene glycol to create prodrugs", ANTI-CAN DR, 14(6), 1999, pp. 499-506

Abstract

The primary purpose of this study was to screen individual amino acid spacers in polyethylene glycol (PEG) conjugated camptothecin for their impact on the conjugates' antitumor activity, Secondly, an active member of this series was used to assess the PEG-camptothecin conjugate's efficacy against abattery of solid tumor types, PEG-camptothecin is a novel water soluble transport form (macromolecular prodrug) of the naturally derived antitumor drug, 20-(S)-camptothecin (CPT), Rates of hydrolysis were studied in phosphate buffered saline (PBS) and the plasma of both rats and humans. In vivo efficacy screens were performed against P388/0 murine leukemia and LS174T human colon solid tumor xenograft models, The results showed that while all thederivatives had considerable stability in PBS, their rates of hydrolysis varied in both rat and human plasma according: to the amino acid spacer employed. Not surprisingly, changing the amino acid also affected in vivo toxicity and efficacy in the treatment of ascites and solid tumors, A representative of this amino acid series, PEG-alanine-CPT, which showed moderate activity in the solid tumor screen, was chosen for evaluation of efficacy across a wide range of solid tumor types and demonstrated significant antitumor activity (%TIC < 30%) in all tested xenograft models (colon, ovarian, mammary, lung, pancreatic and prostate). Therefore, this study showed that the use of specific amino acid spacers affected both the PEG-camptothecin conjugates' breakdown and biological activity. We anticipate that using these insights, this soluble macromolecular transport technology could be successfully employed with a number of antitumor drugs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 19:39:13