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Polymer Drug-Carrier System
targeted drug illustration
TheraTarget, Inc., has unique capabilities and expertise in creating polymer drug-carrier systems that effectively deliver drugs via the blood stream to treat various forms of cancer through a solid tumor targeted approach. This technology embodies a water soluble degradable polymer drug-carrier that will deliver a variety of bound anti-cancer drugs directly to solid cancer tumors with lower toxicity and higher efficacy than the free anti-cancer drug. When the polymer drug delivery system is used to treat patients, anti-cancer drugs are attached to the polymer backbone. This attachment is achieved at a nanoscopic level through chemical bonds. The drug-carrier backbone provides the means whereby the drugs are distributed throughout the body. Basically, the backbone is the drug’s personal navigator throughout its journey in the body. Once the drug arrives at the site of action, i.e., the tumor, only then can it do the work it was designed to do....targeting the cancer and releasing the anti-cancer drug into the tumor, thus causing the death of the tumor cells.

A polymer drug-carrier, has a number of advantages over currently marketed therapies:

Ø Water Soluble

Ø Non-toxic in blood stream

Ø Targets solid cancer tumors

Ø Releases anti-cancer drugs only in tumor cells

Ø Biodegraded in cells and cleared by the kidneys

Ø Multiple drugs can be attached, giving equal and targeted delivery

 

Polymer Drug-Carrier System Overview

The design of our delivery platform is based on high molecular weight HPMA polymeric molecules containing enzyme degradable bonds in the main chain.  The design features of the biodegradable polymer-drug include:

backbone with EPI

Biodegradable backboneP = HPMA copolymer backbone; GFLG = gly-Phe=Leu=Gly; EPI = Epirubicin

(a) degradable polymer backbone to accommodate a high molecular weight polymeric molecule (106 kDa), (b) longer half-life in the blood stream (33.2 hr) and accumulation in tumor tissue due to the EPR effect caused by the leaky nature of newly formed blood vessels in the tumor; and (c) substantially augmented efficacy due to increased drug concentration in tumor tissue.

 

Status of Ongoing Preclinical Studies

The figure below shows the results of a proof-of-concept study. An anti-cancer drug (epirubicin, EPI) was administered on days 0, 4, and 8 to three groups of nude mice that had been implanted with human ovarian cancer tumors beneath the skin of each rear flank. Group 1 was injected with Saline; Group 2, EPI alone; and Group 3, KT-1 (HPMA+EPI). Following Saline or EPI injection alone, the cancer tumors continued to grow and death occurred around day 20. Following injection of KT-1 the tumors stopped growing and were reabsorbed by 10 days. After 100 days the mice were examined and the tumors had completely disappeared.

Chart-EPI

Epirubicin and KT-1 (HPMA-EPI) treatment in mice implanted with human ovarian tumors. Comparison of in vivo anti-tumor activity on female nude mice bearing A2780 human ovarian carcinoma xenografts Three treatment doses of 5 mg/kg on days 0, 4 and 8 followed by observation for three months.

 

A study entitled “Biodegradable multiblock poly(N-2-hydroxypropyl)- methacrylamide gemcitabine and paclitaxel conjugates for ovarian cancer cell combination treatment” was published in the International Journal of Pharmaceutics also demonstrates significant response rates to TheraTarget's platform. The results demonstrate that degradable  HPMA-gemcitabine (GEM) and HPMA-paclitaxel (PTX) when delivered together are effective in the treatment of a mouse model of ovarian cancer. Figure 4 shows combined treatment of paclitaxel (PTX) and gemcitabine  (GEM) for ovarian cancer tumors in nude mice. Treatments used were: (1) Saline; (2) free drugs (PTX+ GEM); and (3) HPMA-PTX (KT-2) and HPMA-GEM (KT-3). Tumors were totally regressed after administration of Kt-2 and KT-3.

 

graph pax and gem

The combination of two backbone degradable HPMA copolymer-drug conjugates (HPMA-PTX and HPMA-GEM) shows significant superior ovarian tumor inhibitory effect over the combination of PTX and GEM alone.

These preclinical studies demonstrate the superior anti-cancer therapeutic efficacy of TheraTarget’s backbone degradable HPMA copolymer-drug conjugates compared to free drug. Currently, Thera-Target has a portfolio of seven unique chemotherapeutic agents that can be bound to our delivery platform. All of these backbone degradable HPMA copolymer-anti cancer drug conjugates demonstrate prolonged circulating time, enhanced tumor accumulation and safe clearance of the degraded copolymer segments simul-taneously.