Poly ( N - Isopropylacrylamide - Co - Methacrylic Acid ) Nanoparticles for Targeted Drug Deliver

Poly(N-isopropylacrylarnide-CO-methacrylic acid) P(NIPArn/MAA) nanoparticles were investigated as potentiai targetable systems for intravenous drug delivery. The responsive properties of P(NIPAm/MAA) nanoparticles have been characterized using dynamic light scattering (DLS) and responsive adhesion techniques. The hydrodynamic diameter of the nanoparticles decreased with increasing temperature of the aqueous medium. Particle size distributions were Gaussian and relatively monodisperse (GSD < 20 % of the mean diameter). The volume phase transition temperature, Tc, of the nanoparticles was sensitive to the state of ionization of surface groups. Tc increased with increasing pH and decreasing ionic strength of the suspending buffers. The particle concentration of nanoparticles per unit volume was calculated by turbidimetry using Mie theory. The surface hydrophobicity of the nanoparticles was evaluated by partitioning of Rose Bengal on particle surfaces, hydrophobic interaction chromatography (HIC), and partitioning of nanoparticles in PEG/Dextran systems. The surface hydrophobicity of the nanoparticles was found to be greater at 40°C than at 25 OC by each method. The pH dependence of the partitioning of nanoparticles suggested a crossover from a steric to a charge stabilization mechanism when the temperature was raised above Tc. Conductometric titration of the nanoparticles suggests that the majority of charges are due to carboxylate residues. The zeta-potential of nanoparticles showed significant levels of surface charge that increased with increasing MAA content. Neither opsonized nor unopsonized P(NïPAmiMAA) nanoparticles stimulated the consumption of oxygen by human neutrophils suggestuig the absence of phagocytic ceii response whereas polystyrene Iatexes of similar size and surface charge stimulated increased oxygen consurnption by the neutrophils. iv PUBLICATIONS FROM THIS THESIS 1. Moselhy, J., niach, O., Macgregor, Jr., R.B., Wu, X.Y.. "Charactenzation of Interactions of P(NIPArn/MAA) Nanoparticles with Biopolymers, Cells, and Hydrophobie Surfaces", Conference of Canadian Biornaterials Society (Kingston, ON, July, 1998). 2. Moselhy, J., Wu, X.Y., "Characterization of Targetable Polymer Nanoparticles", P h a m . Res. iZ(9):S-266 (1995), AAPS Annual Meeting. 3. Moselhy, J., Wu, X.Y., "Responsive Properties of Polymer Colloids", 78th CSC Conference (Guelph, ON, May 1995). 4. Moselhy, J., Wu, X.Y., "Physicochemical Characterization of Poly(Nisopropylacrylamide-CO-methacrylic acid) Nanoparticles for Potential Dmg Targeting, (in preparation).