Nanoparticulate drug delivery systems: synthesis and characterization of amphiphilic diblock copolymers

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Amphiphilic molecules, such as diblock copolymers, are macromolecules with hydrophilic and hydrophobic blocks. Other macromolecules, called dendrimers, are highly branched macromolecules will a well-defined size, capable of binding drug molecules. These polymers all form nanometre size range, spherical particles: self-associating micelles (macromolecular aggregates), vesicles (an outer membrane composed of copolymer molecules and an inner aqueous core), dendrimers (unimolecular micelles) and nanospheres (solid core particles). These so-called nano-delivery systems can all be loaded with hydrophobic drugs, such as paclitaxel, and some will accommodate hydrophilic drugs, such as cisplatin. Few studies have explored the relationship between the properties of the polymer, the type of nanoparticles formed and the performance characteristics of the nano-delivery system, such as stability, drug release, interaction with blood components, interaction with mucosal tissue surfaces and pharmacokinetics. The goal of the proposed research is to compare the delivery characteristics, blood/tissue interactions and tumor targeting of drug loaded polymeric nanosphere, vesicle, micellar and dendritic formulations following both intravenous administration, and local instillation directly into the bladder for application in the treatment of bladder cancer. Surface modification of nano-delivery systems to confer mucoadhesiveness should target the nanoparticles to bladder tumors. The research objectives are: 1) to investigate the influence of structural features of the polymers on properties and performance characteristics of the drug loaded nano-delivery systems, 2) to determine the factors influencing the interactions of untreated and surface modified nano-delivery systems with blood components and bladder tissue, 3) to evaluate the circulation lifetime, systemic uptake, pharmacokinetics and efficacy of selected formulations administered via IV or into the bladders in animal models.