Development of solid lipid nanoparticles containing ionically complexed chemotherapeutic drugs and chemosensitizers

Abstract

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.