Chemotherapeutic Drugs

About

Background Major challenges of treating ovarian carcinomas by the use of intraperitoneal (IP) chemotherapy (e.g. injecting chemo drugs into the abdominal cavity through a catheter) include how to retain the drug in the cavity for longer periods of time, how to concentrate it onto the tumor nodules growing on the peritoneal surface, and how to enhance its penetration from the free surface of the nodule. Drug loaded nanomaterials are generally obtained by encapsulation of the drug during formulation of the particle via non‐covalent adsorption or passive entrapment. A limitation of these loading strategies is the burst release of drug, where an important fraction of the loaded compound is released in a short amount of time due to the inherently weak forces keeping the drug associated with the nanocarrier. In addition, for metal based drugs, loaded polymeric nanomaterials can be generated via a post‐polymerization reaction of an activated metal complex with an activated ligand moiety on the polymer backbone. In this case, inherent to the technique, is the lack of control of the type of ligand (monodentate, bidentate) and complex (interstrand or intrastrand), which are obtained. However, the main drawback to these approaches is the typically low and uncontrolled encapsulation efficacy, which is a severe limitation for large‐scale production and reproducibility that hinders the development of clinically appropriate formulations.   Technology Description UC San Diego researchers have designed and synthesized a new class of nanoparticles that significantly increase the efficacy of intraperitoneal (IP) chemotherapy through the use of delivery vehicles that are retained for long periods of time in the peritoneal cavity and that are capable of adhering to, and penetrating into, tumor nodules when administered by the IP route. This novel formulation avoids unwanted drug release prior to administration or endocytosis by tumor cells. More importantly, this technology yielded nanoparticles with consistent morphological characteristics with the advantage of offering controlled, reproducible and unprecedented levels of platinum drug loading. This means one can now generate particles of various sizes and shapes that are highly stable until delivered to cells. The morphology of the particles can be used to dictate pharmacokinetic profiles in animals.   This technology represents an entirely new way to incorporate oxaliplatin (L‐OHP) into a polymer backbone that can then be used to make nanoparticles of different shapes. The shape controls both the peritoneal retention of the nanoparticles and the ability to adhere to and penetrate into tumor nodules. Specifically, the inventors have synthesized a novel oxaliplatin analogue containing a norbornyl moiety amenable to polymerization via ring opening metathesis polymerization (ROMP). The covalently bound platinum (Pt) (II)‐loaded polymers self‐assemble into well‐defined nanoparticles in aqueous solution in a highly reproducible manner.   Applications Potential nanoparticle pro-drug delivery system for ovarian cancer and other abdominal cancers   Advantages This new class of nanoparticles significantly increase the efficacy of intraperitoneal (IP) chemotherapy through the use of delivery vehicles that are retained for long periods of time in the peritoneal cavity and that are capable of adhering to, and penetrating into, tumor nodules when administered by the IP route. Furthermore, the covalently modified drug‐carrying NPs show cytotoxic activity against human tumor cells comparable to the parental drug oxaliplatin and to cisplatin, while they also showed slow in vitro Pt(II)‐ release kinetics. While this new technology is not limited to just the Pt(II)-prodrugs,  it may be of wider commercial interest to both drug delivery companies and big pharma in the ovarian cancer space as well as other abdominal cancers   State Of Development Currently at the experimental stage, the inventors are optimizing the nanoparticle targeting system and the self‐assemble process into different shaped nanomaterials. Moreover they are also investigating the processes which triggers NP disassemble in the cell by tracking the carrier and the drug separately.   Intellectual Property Info UC San Diego is looking for companies to commercialize this technology. US Patent Rights are available.