Ceramoptec Industries, Inc.

J&ouml;rg G Moser

Wolfgang Neuberger

Ralph Hoffmann

The present invention provides a drug delivery system wherein a &ldquo;parachute&rdquo; structure is coupled to a therapeutic compound. The &ldquo;parachute&rdquo; structure comprises hydrophilic branched molecules with a defined action diameter. The complex (a parachute structure coupled with a therapeutic compound) is either fixed at a cell membrane or delivered to a defined distance from the membrane within the cell. The membrane-anchoring/localizing effect of the parachute is achieved by hydrophilic structures linked with a branching unit of desired therapeutic compounds. Furthermore, the parachute structures can be connected by a spacer (e.g. &bgr;-amino acids, &ggr;-amino butyric acid, or poly-amino acids) instead of directly binding to the therapeutic compound, so that the therapeutic compounds can be localized within the cells at a defined distance from the cell membrane. A spacer containing a breaking point can determine the time span, during which the drug exhibits its therapeutic activity. The hydrophilic residues can also carry signals for targeting the parachute-therapeutic complex to a defined tissue type. This can be mediated by an antibody which is specific for a tumor marker. Alternatively, a Biotin can be attached at C6 position of the sugar and then react with an Avidin-labeled tumor-specific antibody. The parachute function may also be achieved by other, more bulky hydrophilic structures such as oligosaccharides connected to the branching unit. Such sugar oligomers have specific attachment points to cell selectins, and therefore do not need additional molecular structures to target a specific tumor tissue. The use of the parachute structure gives the advantages of being able to localize a photosensitizer or chemotherapeutic drug at the site within a cell where it can destroy the tumor cell most effectively. This reduces the level of necessary systemic doses of the drugs, promotes drug excretion, and therefore considerably reduces side effects of the therapy.

Photosensitizers with ligand targeting properties for tumor therapy

A drug delivery system and methods are provided wherein a therapeutic/diagnostic agent or a component of the immune system is directed to particular cells in a selected organ or a specific site. Such a system can be formed by a photoselective compound generally described as V-M-P-C. V is a vector component suitable to target particular cells in a selected organ or site, where the type of the cell or antigen does not have to be specific to the desired treatment site. M is a marker component that is capable of being targeted by a therapeutic/diagnostic agent or a component of the immune system. P is a photocleavable or photosensitive bond, and C is a cap component rendering M ineffective. C is connected to M by the photocleavable or photosensitive bond. The photoselective compound is administered and marks targets of a certain kind of cell or a specific site. Then radiation of a specific wavelength or wavelength range is applied to the geometric volume that is to be treated, uncapping the M sites in the desired treatment volume. Therapeutic or diagnostic agents can be subsequently or concurrently administered in a form that specifically targets the uncapped sites of M. The therapeutic or diagnostic agent can be a drug, a radioactive compound, a fluorescent compound or a photosensitiser. Additional components, such as multiplier molecules, can also be inserted into the basic V-M-P-C scheme. Moreover, the marker component can be such that after the removal of the cap component, components of the immune system can bind to M and thus concentrate at a desired site. The present invention facilitates the delivery of therapeutic/diagnostic agents or components of the immune system to particular cells in a selected organ or a specific site, and therefore, minimizes the potential harmful effect of the agents to the normal cells in the rest of the body.

Photoselective marking of biological targets

A rigidly spaced, cyclodextrin dimers having a preselected breaking point within the spacer sequence so as to controllably release the active pharmaceutically active substance only after it reaches the desired treatment site is described. These preselected breaking points are stable in blood but are cleavable within cells. In preferred embodiments, the cyclodextrin-pharmaceutically active substance complex is targeted to specific sites via incorporation of specific antibodies for the targeted sites, typically by complexing a biotin-avidin system to specific antibodies which thereby targets the complex to a specific site. Once at the site as the complex is taken up into the cell the preselected break point is cleaved and the encapsulated pharmaceutically active substance becomes available for action within the targeted cell. This approach permits the use of highly effective and efficient pharmaceutically active substances, whose safety restricts use to last chance efforts or which are unable to qualify for human use due to their potential side effects. In a preferred embodiment peptide structures are used as part of the spacers between bridged cyclodextrins The cyclodextrin oligomers are complexed with pharmaceuticals with potential high side effects to safely, efficiently achieve the therapeutic action dsired.

Growing community of inventors

Düsseldorf, Germany

Jörg G Moser

Growing community of inventors

Düsseldorf, Germany

J&ouml;rg G Moser

Jörg G Moser