A Hyaluronan-Based Nanoparticle Cisplatin Delivery System

Background: In patients with ovarian cancer, injection of chemotherapeutic agents (CAs) into the peritoneal cavity helps target CAs to tumor nodules growing on the peritoneal surface. Clinical trials utilizing the intraperitoneal injection of CAs has been shown to increase survival in patients in whom most of the tumor is surgically removed. Several systems have been successfully used to increase drug retention in the peritoneal cavity while reducing the rate at which they enter the systemic circulation. A need remains for better drug carriers capable of attaching to the cells of tumor nodules growing on the peritoneal surface.

Technology Description: UC San Diego researchers have addressed this need and developed a microparticle loaded with large amounts of cisplatin that can attach itself to CD44, a receptor highly expressed on many ovarian cancer cells. This releases the drug in high concentrations locally and reduces the amount of drug reaching normal tissues.

Specifically, this invention discloses a formulation and a method for preparing a nanocomplex consisting of cisplatin (a platinum-based chemotherapy drug) and hyaluronan. Hyaluronan is a known ligand for CD44 (a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion, and cell migration) and therefore, the nanocomplex can deliver cisplatin to CD44-expressing cells in a targeted manner.

The disclosed formulation and method provided allows highly efficient incorporation of cisplatin into a nanoparticle made up of a polysaccharide that is known to bind selectively to cells expressing the hyaluronan receptor CD44. CD44 is expressed on many types of malignancies. The disclosed nanocomplex allows targeting of the cisplatin into receptor positive cells. The nanocomplex also exhibits a significantly reduced clearance from the peritoneum compared to free cisplatin and improved efficacy in a murine model.

Advantages: Cisplatin is one of the most widely used chemotherapeutic drugs. It is used both intraperitoneally for the treatment of ovarian cancer and intravenously for the treatment of many other types of malignancies including lung, bladder, head, and neck cancers.

This novel nanocomplex may replace cisplatin for the intraperitoneal treatment of ovarian cancer and possibly other malignancies, and may potentially be more effective than free cisplatin when given intravenously for other types of cancers.

State of Development: Patent pending. This invention is available for licensing.

Case Number: SD2009-190

Inquiries To: invent@ucsd.edu