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Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30–32 weight percentage of gentamicin. The zeta potential changed from −39 to −13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log 10), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log 10). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B.melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers. [ABSTRACT FROM AUTHOR]

Magnetic block ionomer complexes (MBICs) containing acombinationof therapeutic and imaging agents are of great interest for deliveringdrugs and tracking their biodistribution with magnetic resonance imaging.With an aim to develop nanocarriers with high drug loadings that integratemagnetic nanoparticles into one system, we herein report antibiotic-ladenMBICs based on assembly of poly(ethylene oxide-b-acrylate)(PEO-b-PAA) ionomers with nanomagnetite and gentamicin.The polymer was bound to the magnetic nanoparticle surfaces via ligandadsorption of the PAA block, thereby creating a double corona structurewith a nonionic PEO shell and an ionic region rich in PAA. The portionof carboxylates that were not bound to the magnetite provided bindingsites for drug loading via ionic complexation. PEO was chosen as ablock copolymer segment to improve biocompatibility and aid in dispersionthrough interparticle steric repulsion. Intensity average diametersincreased from 34 to 62 nm upon adding the drug, suggesting that theparticles formed small clusters. Zeta potentials decreased from approximately−40 without gentamicin to approximately −10 mV withthe drug, indicating that the drug effectively localized the chargesin the MBIC cores. Approximately 35 wt % of the encapsulated gentamicinwas released under physiological conditions within 10 h, and thiswas followed by slower release of another 7% by 18 h. The solid magnetitecore serves as a multifunctional substrate for block ionomers to stablyadsorb, thus acting as a pseudo-crosslinking site in the complexesthat enhances their stability. Complexes between PEO-b-PAA and gentamicin without magnetite instantaneously dissociatein saline buffer. When the same copolymer was adsorbed onto magnetite,subsequent complexation with gentamicin resulted in stable complexesthat withstood media with physiological ionic strength. [ABSTRACT FROM AUTHOR]