Multistep, effective drug distribution within solid tumors

摘要: The distribution of drugs within solid tumors presents a long-standing barrier for efficient cancer therapies. Tumors are highly resistant to diffusion, and the lack blood lymphatic flows suppresses convection. Prolonged, continuous intratumoral drug delivery from miniature source offers an alternative both systemic injection. Presented here is model such source, in multistep process. At onset mainly affects closest surroundings. Such 'priming' enables penetration successive cell layers. Tumor 'void volume' (volume not occupied by cells) increases, facilitating perfusion. then transported hydraulic convection downstream along interstitial fluid pressure (IFP) gradients, away tumor core. After week death occurs throughout entire IFP gradients flattened. Then, 'mixing', powered physiological bulk body movements. Steady state achieved covers over several months. Supporting measurements provided LODER system, releasing siRNA against mutated KRAS months pancreatic in-vivo models. was also successfully employed recent Phase 1/2 clinical trial with patients.