In-vivo and in-vitro targeting of a murine sarcoma by gelatin microparticles loaded with a glycan (PS1).
PS1, a complex polysaccharide derived from Mycobacterium bovis (Bacillus Calmette-Guérin, BCG) with considerable antitumor activity in-vivo, was loaded onto gelatin microparticles (mean diam. 1.45 micron) at a level shown to not produce the burst effect often seen with drug-loaded microparticulate systems. In-vitro dissolution experiments had demonstrated a sustained-release behaviour, with a half-life of approximately 8 h for what is an extremely water-soluble material. These PS1/gelatin systems had no measurable cytotoxicity against an S180 murine sarcoma cell in-vitro although fibronectin-mediated targeting of the microparticles for the tumour cells could be demonstrated. Injection into mice, with the S180 cells, of PS1 solutions or suspensions of PS1-loaded gelatin microparticles resulted in almost identical dose-related suppression for the tumour cell growth. When injected at intervals following injection of the tumour cells, however, for a period of 24-48 h there was a relatively enhanced activity of the formulated PS1, compared with the aqueous solution, after which both formulated and unformulated material became progressively less effective.
Lou
Y
Y
Institute of Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago 60607-7019.
Groves
M J
MJ
Klegerman
M E
ME
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005780:Gelatin; D006207:Half-Life; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000737:chemistry; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D009163:Mycobacterium bovis; D011134:Polysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D012510:Sarcoma 180 / Q000378:metabolism*
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005353:Fibronectins; D008070:Lipopolysaccharides; D011134:Polysaccharides; D005780:Gelatin