NANO-PARTICLE MEDIATED DRUG DELIVERY TO SOLID TUMORS

Cyclosert™  forms nanoscale constructs with hydrodynamic diameters between 30 and 60 nanometers.   This makes Cyclosert™ based drugs ideal for effective delivery to solid tumors.  The defined nanoscale size together with the highly hydrophilic character of the Cyclosert polymers allows the constructs to accumulate in tumor through a mechanism called the “Enhanced Permeability and Retention” (EPR) effect.  The EPR effect can be attributed to two factors: long-circulating nano-particulate drugs are able to (A) escape the vasculature through abnormally leaky tumor blood vessels and are (B) subsequently retained in the tumor tissue due to a lack of effective tumor lymphatic drainage.

Nanoparticulate drugs with a size greater than 10 nanometers avoid kidney clearance resulting in prolonged and elevated levels in the blood stream.   The upper limit for particle size is approximately 100 nanometers in order to allow the particles to pass out of the blood vessels and diffuse within the tumor tissue. Calando has demonstrated that nanoscale Cyclosert™ conjugates can dramatically improve the tumor localization of small molecule drugs in animal models of human cancer.  We have also shown that this results in extended release of active drug within the tumor tissue.

Release kinetics of the active drug from the Cyclosert™ drug construct are dependent on the type of linker used.  Optimization of the release kinetics allows Calando to enhance efficacy and reduce unwanted side effects of chemotherapeutic drugs.  Release of drug at the target site over extended periods of time enhances the efficacy of drugs that have cell cycle dependent activity, because not all target cells may be cycling at any given time.  On the other hand, low levels of circulating free drug are desirable to minimize side effects.