Targeted drug delivery based on the mode of action of bacillus Calmette-Guerin in bladder cancer

Morales, Lamm and others have shown conclusively that viable, attenuated Mycobacterium bovis, strain BCG (BCG vaccine), instilled in saline into the bladder of patients with primary superficial bladder cancer, is the therapeutic treatment of choice. Amongst the issues with producing and administering BCG are those of demonstrating the purity of the product, i.e., BCG and no other organism, and of estimating the actual dose delivered. Both can be achieved by automated gas chromatographic analysis of the methyl esters of fatty acids between C9 and C20. The cell mass of BCG is here shown to be proportional to the area under the gas chromatographic detector curve for the palmitic acid methyl ester.;Nonviable, gelatin-bearing microspheres would be preferable to bacille Calmette-Guerin because the microspheres can be prepared as sterile materials and can be loaded with immunopotentiators, or chemotherapeutic drugs, or antibiotics, or combinations of these. Sterile preparations pose a minimal threat to immune-compromised patients as compared with viable BCG, may be less expensive, and may be applicable in the treatment of cancers other than bladder tumors.;Ratliff and co-workers have promoted compelling arguments and data to show that BCG binds to sites in the bladder of patients with primary tumors. Ratliff's research supports the theory that BCG binds to fibronectin located on or near superficial bladder tumors. Immobilized gelatin is used in the bioaffinity purification of fibronectin, hence the proposal of this thesis that particles bearing gelatin should interact with fibronectin on surfaces in the area of a superficial bladder tumor. Various lots of Tice...