Disulfide cross-linked fab-aggregates: Preparation and biodistribution
JOURNAL OF DRUG TARGETING, vol.6, no.1, pp.45-52, 1998 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 6 Issue: 1
- Publication Date: 1998
- Doi Number: 10.3109/10611869808997880
- Journal Name: JOURNAL OF DRUG TARGETING
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.45-52
- Hacettepe University Affiliated: No
Abstract
The high-molecular-weight soluble aggregates of Fab fragments of murine antibodies against cardiac myosin were prepared as a potential long-circulating and low Immunogenic pharmaceutical carriers by conjugation of thiolated Fab and Fab modified with succinimidyl 3-(2-pyridyldithio)propionate. The clearance time and biodistribution of In-111-radiolabeled aggregates were studied in normal and nude-mice bearing human breast tumor implant and in rabbits with experimental myocardial infarction. The aggregates had a prolonged circulation time (half clearance time ca. 3-5 h) and ability to concentrate in the tumor and in the necrotic area of infarcted myocardium. Similar tumor-to-normal and infarct-to-normal accumulation ratios (ca. 3 h in both cases) suggest that combination of long circulation with impaired filtration in necrotic tissues is responsible for this accumulation rather than a specific interaction. The aggregates prepared may serve as long-circulating drug carriers able to deliver pharmaceuticals into areas with affected and leaky vasculature.