The purpose of this study was to develop and characterize a solid
lipid nanoparticle (SLN) system containing an anionic
polymer for the delivery of cationic
antineoplastic agents and chemosensitizers. Ionic complexation was utilized to enhance the loading of these highly water-soluble drugs. The influence of anionic compounds and
polymers on
drug partition and loading into SLNs was investigated, and
dextran sulfate (DS) was found to be the most suitable among those studied. SLNs loaded with
doxorubicin and various model chemosensitizers (e.g.,
verapamil) were thus prepared by incorporating DS using a microemulsion method. The particle size was measured with photon correlation spectroscopy. The mean diameter of the SLNs ranged from 180 to 300 nm, depending on the type and content of the
drug and the
polymer. The particles possessed weakly negative surface charges as determined by zeta potential measurements. Most
polymer-loaded SLNs released half of the
drug in the first a few hours and the remaining
drug in 15 h or more. The presence of counterions in the medium, especially divalent
ions, promoted drug release. Dual
drug (
doxorubicin/
verapamil or
quinidine/verapamil)-loaded DS-SLNs were also formulated, which released both drugs without noticeable interference to each other. These studies have laid the foundation for a "one-bullet"
dosage form that may provide convenient and effective delivery of multiple
drug treatment of
tumors.