Characterization of polyacrylamide nanoparticles for biomedical applications: Toxicology, pharmacology, and therapy.

摘要

Polyacrylamide (PAA) nanoparticles have been developed for real-time intracellular measurements with applications for analysis of drug, toxin, and environmental effects on cell function. Chemically, the flexibility and ease of synthesis of PAA nanoparticles has also led to their development for imaging tumors and the simultaneous in situ treatment of cancer. The matrices are composed of cross-linked polyacrylamide. Due to their novelty, the toxicology, pharmacology, and therapeutic potential have not been defined. Therefore, this thesis tests the toxicology (biocompatibility) and pharmacology (pharmacokinetics, tissue distribution, and excretion), of the polyacrylamide matrix after intravenous administration into a rodent model. In addition, this thesis tests the utility of the polyacrylamide nanoparticle in photodynamic therapy (PDT) for treating cancer. Data acquired in this thesis provide evidence that nanoparticles comprised of polyacrylamide are non-toxic after i.v. administration. Pharmacokinetic results indicate that the reticular endothelial system is responsible for removing a significant percentage of the administered dose. The stability of the matrix indicated prolonged degradation and as a result modest recovery in the excrement. In addition, because the matrix is a polymer (foreign body) and exhibits long-term exposure to the R.E.S, immunologic responses associated with inflammation and recruitment of antigen presenting cells (APC) were measured. Results from these data do not implicate the polymer, after sequestration into the RES, with inflammatory signaling or trafficking of dendritic cells to the liver or spleen. Additional experiments provide evidence of hepatic sinusoidal-lymph translocation of a percentage of the administered dose to the portal lymph node.; Development of these nanoparticles for PDT proved successful at the in vitro level. Results indicate that polyacrylamide nanoparticles, carrying a photosensitive dye are capable of producing sufficient amounts of singlet oxygen and inducing cell death in a resistant cell model for brain cancer.; These data provided in this dissertation characterize polyacrylamide nanoparticles for future development as a device in various biomedical applications. The polymer matrix is biocompatible, non-immunogenic and therapeutically attuned for utilization in PDT.