Targeted delivery of immunomicrospheres in vivo

Vu L. Truong, Jerry R. Williams, James Hildreth, Kam W. Leong

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The feasibility of targeted delivery of bioactive agents using microspheres made of enzymatically degradable gelatin/chondroitin sulfate was investigated. The microspheres, synthesized by complex coacervation under mild aqueous conditions, exhibited high loading level for a variety of agents. Monoclonal anti-bodies against P-glycoprotein (Pgp), lymphocyte function associated antigen-1 (LFA-1), and thrombomodulin (TM) were attached to the microsphere surface using avidin and biotin as the linkage system. Anti-Pgp mAb-coated microsphere encapsulated with photofrin II destroyed Pgp-positive KB-V-1 cells 24 times more efficient as compared to the free drug in vitro. The binding and destruction of KB-V-1 cells were cell tar-get selective and antibody dependent. Electron microscopy studies showed that colloidal gold-encapsulated microspheres coated with anti-Pgp mAb were internalized by KB-V-1 cells within 4 h after binding. The target selectability of this immunomicrosphere delivery system was also demonstrated in vivo. 90Yttrium-labeled microspheres were targeted to the pulmonary vascular endothelial cells of mice using anti-TM mAb, and to the leukocytes using anti-LFA-1 mAb. A total of 67.5% of anti-TM mAb coated microspheres (injected dose per gram wet tissue weight) was localized to the lung within 1 h after injection, while 20.2% of anti-LFA-1 mAb-coated microspheres was associated with the blood compartment.

Original languageEnglish (US)
Pages (from-to)166-174
Number of pages9
JournalDrug Delivery
Volume2
Issue number3-4
DOIs
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology

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