Novel metal-based anticancer drugs: a new challenge in drug delivery

Since the serependitous discovery of the cisplatin antiproliferative activity, many efforts have focused on the design of potent metal-based drugs for oncology therapies. A large number of these complexes have been evaluated in vitro and in vivo and some have reached clinical trials. However, while metallodrug chemistry has developed to an advanced level, these emerging therapeutics have encountered new hurdles including poor water solubility and pharmacological deficiencies. Today, solutions to overcome these issues do not lie in synthesizing new anticancer drugs but in finding suitable drug delivery strategies. Over the past decades, various delivery systems have been developed including prodrug, ligand design and nanocarriers aimed at enhancing the performance profile of these novel metallodrugs

Brain Tumors: Convection-Enhanced Delivery of Drugs (Method)

Delivery of therapeutic agents into the brain has been an ongoing challenge for many years. The poor prognosis for patient with primary malignant brain tumors treated with conventional techniques (surgery, radiotherapy and chemotherapy) has motivated the development of new strategies to deliver drugs into the brain. Local intracranial delivery of antineoplastic agents has appeared to be the most effective drug delivery technique into the central nervous system by circumventing the limitations imposed by the blood brain barrier (BBB). Convection-enhanced delivery (CED) is an alternative strategy to directly infuse drugs into brain tissue. This approach is based on continuous injection of the therapeutic agent under positive pressure via a catheter implanted into the brain. Convective transport driven by pressure gradient allows a widespread distribution of small and large drugs within the brain. In vivo experiments in rodents, cats and primates proved the efficacy of CED to deliver drugs into a targeted zone. However, clinical trials have reported frequent leakage phenomenon leading to mixed results for this delivery technique. A better optimization of operational parameters including infusion rate, catheter design, catheter placement and drug pharmacological formulation should allow achieving accurate and efficient delivery. In conjunction with CED, the use of nanocarriers to enhance drug pharmacokinetic behavior may help to achieve higher therapeutic index against tumor cells over healthy tissues. Additionally, the development of computer simulation to predict drug distribution and the real-time imaging for immediate assessment of convection efficiency may contribute to the CED improvement