(286c) Magnetic Block Ionomer Complexes for Imaging and Therapeutics

Multifunctional nanocarriers comprising a combination of therapeutic and imaging agents are of great interest for delivering drugs and tracking their biodistribution. With an aim to develop nanocarriers with high drug loadings that integrate magnetic nanoparticles for imaging into one system, we report on 2 types of antibiotic-laden magnetic block ionomer complexes based on assembly of block ionomers with nanomagnetite and cationic drugs. One type of complex - magnetic block ionomer complex (MBICs) - consisted of aggregates of superparamagnetic magnetite nanoparticles held together by noncovalent forces. The second type of complex - magnetic block ionomer clusters (MBIClusters) - were held together by covalent crosslinks between polymer chains. In both cases, the magnetite core was synthesized via reduction of an Fe(III) organometallic precursor. Nonionic-ionic block copolymers were synthesized through controlled free-radical polymerization (ATRP). The polymer was bound to the magnetic nanoparticle surfaces via ligand adsorption of the PAA, thereby creating a double corona structure with a nonionic PEO shell and an ionic layer of PAA. The portion of carboxylates that were not attached to the magnetite provided binding sites for drug loading via ionic complexation. In the case of the MBIClusters, amine groups at the tips of the H₂N-PEO corona chains were subsequently crosslinked through reaction with a poly(ethylene glycol) diacrylate oligomer to yield clusters. The nanoscale average sizes of the clusters were controlled by adjusting the concentration of the reactants in the crosslinking step.

For both classes of complexes, gentamicin (a multi-cationic drug) was employed as model for encapsulation. Results suggest that the MBICs are sufficiently stable in physiological conditions to be suitable as drug carriers. Dispersions of the MBICs were stable in PBS containing 0.14 M NaCl for up to 10 days, and were stable in PBS containing fetal bovine serum (FBS). Physicochemical properties of the MBICs were significantly altered upon gentamicin encapsulation (31 wt % drug). A near zero-order release of gentamicin (pH 7.4 in PBS) that reached ~35 wt% of the initial gentamicin within 10 h was observed, and this was followed by slower release of another 7% by 18 h. The unloaded complexes (no drug) had a transverse relaxivity of 82 s^-1(mM Fe)^-1, which is ~ 2X higher than that reported for commercial T₂ contrast agents at 37 °C and 1.5 T. The increase in size of the complexes upon gentamicin encapsulation was accompanied by an increase in r₂ to 161 s^-1(mM Fe)^-1.  The increase in r₂ with formation of small aggregates is consistent with recent findings in our group that controlled aggregation leads to considerably shorter T₂ relaxation times or higher r₂ relaxivities. Gentamicin loading in the MBIClusters was as high as 38 wt%, corresponding to a drug loading efficiency of ~ 95%. The MBIClusters exhibited markedly high transverse relaxivities (r₂) ranging from 190 to 604 s^-1 mMFe^-1. The effect of cluster size on relaxivity will be discussed.