Synthesis and in vitro evaluation of self-assembling biocompatible heparin-based targeting polymeric micelles for delivery of doxorubicin to leukemic cells.

Background and purpose: Biodegradable polymeric micelles have emerged as one of the most promising platforms for targeted drug delivery. In the present study, a polymeric micelle composed of folic acid (FA), heparin (HEP), dexamethasone (DEX), and (FA-PEG-HEP-CA-TOC) was developed for the delivery of doxorubicin (DOX) to leukemic cells.

Experimental approach: FA-HEP-DEX was synthesized and characterized by 1H-NMR. DOX-loaded micelles were prepared using a dialysis method. The impact of various processing variables, including polymer-to-drug ratio, dialysis temperature, and solvent type, on the physicochemical properties of the micelles were evaluated. In vitro, cellular uptake and cytotoxicity of the micelles in folate receptor-positive (K562) and negative (HepG2) cells were evaluated.

Findings/results: The 1H-NMR results confirmed the successful synthesis of FA-HEP-DEX. DOX-loaded micelles exhibited an average particle size of 117 to 181 nm with a high drug entrapment efficiency (36% to 71%). DOX-loaded micelles also showed sustained drug-release behavior. DOX-loaded FA-HEP-DEX micelles exhibited higher cellular uptake and in vitro cytotoxicity than free DOX and DOX-loaded HEP-DEX micelles in K562 cells.

Conclusions and implications: DOX was well incorporated into the micelles with high entrapment efficiency due to high solubility of DOX in DEX as the hydrophobic component of the micelle structure. The higher cellular uptake and cell toxicity of targeted micelles correspond to the presence of FA on the micelle surface, which promotes cell internalization of the micelles viaspecific receptor-mediated endocytosis. Our results indicated the potential of DOX-loaded heparin-based micelles with desirable antitumor activity as a targeted drug delivery system in cancer therapy.