Tumor targeting with polymeric molecules having extended conform

Details Tumor targeting with polymeric molecules having extended conform Tumor targeting with polymeric molecules having extended conform

1996-08-01

1998-06-09

Kight, John

Drug, bio-affecting and body treating compositions

In vivo diagnosis or in vivo testing

Magnetic imaging agent

424 91, 424 93, 424 165, A61K 4900, G01N 3100, G01N 3348

Patent

active

057629099

ABSTRACT:
Enhanced drug delivery to tumor tissue is obtained by attaching drug molecules to elongated polypeptide carrier molecules several orders of magnitude longer than wide. These are chosen to have a high net negative charge. The carrier molecules are created by unfolding long polypeptides by a large degree of substitution with steric hindrance molecules, such as diethylene triamine pentaacetic acid (DTPA) with at least 90% substitution. This causes the conformation to be worm-like as evidenced by a measure of persistence length, with a diameter small enough squeeze through the pore structures of tumor tissue but not so small as to pass through pores of vessels in normal tissue. The length is determined by optimizing two processes, blood circulation lifetime, and tumor uptake. The elongated conformation may cause the complex to become entwined with stroma in tumor interstitium and become trapped. The complex molecules provides increased therapeutic benefit in effecting tumor tissue destruction, or may be used in enhancing imaging contrast depending upon the active agent attached to the carrier molecules. The enhanced concentration and retention of the complex molecules within the tumor reduces side effects of the active agent in other tissues.

REFERENCES:
patent: 4855353 (1989-08-01), Kurami et al.
patent: 5534241 (1996-07-01), Torchilin et al.
patent: 5554748 (1996-09-01), Sieving et al.
patent: 5593658 (1997-01-01), Bogdanov et al.
Uzgiris (Feb. 1995), Biophysical Journal, vol. 68, No. 2, Part 2, Abstract #442 "Effects of Charge and Conformation on Macromolecule Uptake by Tumors".
Shih et al (1988), Int. J. Cancer, vol. 41, pp. 832-839, "Site Specific Linkage of Methotrexate to Monoclonal Antibodies Using An Intermediate Carrier".
Rosenthal et al (1993), Investigative Radiology, vol. 28, No. 9, pp. 789-795, "The Demonstration of Human Tumors on Nude Mice Using Godolinium Labeled Monoclonal Antibodies for MR Imaging".
Pratesi et al (1985), J. Cancer, vol. 52, pp. 841-848, "Poly-L-Aspartic Acid as a Carrier for Doxorubicin Drug Comparative in vivo Study of Free and Polymer Bound Drug".
Sieving et al (1990), Bioconjugate Chem., vol. 1, No. 1, pp. 65-71 "Preparation and Characterization of Paramagnetic Polychelates and their Protein Conjugates".
Primm (1988), Critical Reviews in Therapeutic Drug Carrier Systems, vol. 5, No. 3, pp. 189-227, "Drug Monoclonal Antibody Conjugates for Cancer Therapy: Potentials and Limitations".
Opsahl et al (Mar. 1994), Biophysical Journal, vol. 66, No. 2, Part 2, Abstract #81, "Dynamics of NMR Contrast Agent Uptake by Tumors".

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