IT-141, a Polymer Micelle Encapsulating SN-38, Induces Tumor Regression in Multiple Colorectal Cancer Models

Polymer micelles are promising drug delivery vehicles for the delivery of anticancer agents to tumors. Often, anticancer drugs display potent cytotoxic effects towards cancer cells but are too hydrophobic to be administered in the clinic as a free drug. To address this problem, a polymer micelle was designed using a triblock copolymer (ITP-101) that enables hydrophobic drugs to be encapsulated. An SN-38 encapsulated micelle, IT-141, was prepared that exhibited potent in vitro cytotoxicity against a wide array of cancer cell lines. In a mouse model, pharmacokinetic analysis revealed that IT-141 had a much longer circulation time, plasma exposure, and tumor exposure compared to irinotecan. IT-141 was also superior to irinotecan in terms of antitumor activity, exhibiting greater tumor inhibition in HT-29 and HCT116 colorectal cancer xenograft models at half the dose of irinotecan. The antitumor effect of IT-141 was dose-dependent and caused complete growth inhibition and tumor regression at well-tolerated doses. Varying the specific concentration of SN-38 within the IT-141 micelle had no detectible effect on this antitumor activity, indicating no differences in activity between different IT-141 formulations. In summary, IT-141 is a potent micelle-based chemotherapy that holds promise for the treatment of colorectal cancer

A Versatile Polymer Micelle Drug Delivery System for Encapsulation and In Vivo Stabilization of Hydrophobic Anticancer Drugs

Chemotherapeutic drugs are widely used for the treatment of cancer; however, use of these drugs is often associated with patient toxicity and poor tumor delivery. Micellar drug carriers offer a promising approach for formulating and achieving improved delivery of hydrophobic chemotherapeutic drugs; however, conventional micelles do not have long-term stability in complex biological environments such as plasma. To address this problem, a novel triblock copolymer has been developed to encapsulate several different hydrophobic drugs into stable polymer micelles. These micelles have been engineered to be stable at low concentrations even in complex biological fluids, and to release cargo in response to low pH environments, such as in the tumor microenvironment or in tumor cell endosomes. The particle sizes of drugs encapsulated ranged between 30–80 nm, with no relationship to the hydrophobicity of the drug. Stabilization of the micelles below the critical micelle concentration was demonstrated using a pH-reversible crosslinking mechanism, with proof-of-concept demonstrated in both in vitro and in vivo models. Described herein is polymer micelle drug delivery system that enables encapsulation and stabilization of a wide variety of chemotherapeutic drugs in a single platform

Functionalized quantum dots for dispersion in polymers and cross -linking at interfaces

Quantum dots are attractive potential components for next generation technologies such as light emitting diodes, sensors, and photovoltaic cells due to their unique and tunable electro-optical properties. The effective integration of quantum dots into devices requires a stable dispersion or self-assembly of the quantum dots in the solid-state. Such dispersions or assemblies are dictated by the interactions between the ligand environment of the quantum dots and the chosen polymer matrix. This thesis will highlight key contributions to the area of tailored cadmium selenide nanocrystals through the use of novel, functionalized ligands. This includes the utilization of ring-opening metathesis polymerization (ROMP), reversible addition fragmentation chain-transfer (RAFT) polymerization, and metal mediated couplings to control the polymer composition and molecular weight in radial polymerizations from CdSe nanocrystals. CdSe quantum dots were also found to assembly at the interface of immiscible fluids, and through appropriately functionalization these assemblies were effectively cross-linked. The key fording in this work is the retention of the inherent quantum dot fluorescence following these polymerization methods

Functionalized quantum dots for dispersion in polymers and cross-linking at interfaces.

Polymer Science and EngineeringDoctor of Philosophy (PhD

The use of 4-substituted pyridines to afford amphiphilic, pegylated cadmium selenide nanoparticles

Amphiphilic cadmium selenide (CdSe) nanoparticles were prepared by surface functionalization with novel ligands 1 and 2, composed of pyridine moieties substituted in the 4-position with polyethylene glycol (PEG) chains