Development of Traceable Rituximab-Modified PEO-Polyester Micelles by Postinsertion of PEG-phospholipids for Targeting of B-cell Lymphoma

The objective of this work was to develop rituximab (RTX)-modified polymeric micelles for targeting of B-cell lymphoma cells, through postinsertion of RTX-poly(ethylene glycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (RTX-PEG-DSPE) into methoxy poly(ethylene oxide)-poly(e-caprolactone) (PEO-PCL) or methoxy poly(ethylene oxide)-poly(e-benzylcarboxylate-e-caprolactone) (PEO-PBCL) micelles. Mixed micelles were made traceable by introducing Cy5.5 to RTX and conjugating Cy3 to propargyl moiety, end-capped PCL or PBCL. Successful adaptation of the postinsertion method for the formation of immunomicelles was evidenced by measurement of RTX levels on the micellar surface, purified from free RTX by size exclusion chromatography, using microBSA assay. A change in the micellar diameter, from 50–70 nm for PEO-PCL and PEO-PBCL micelles and 20 nm for PEG-DSPE micelles, to 80–95 nm for the mixed micellar population as well as the critical micellar concentration of mixed micelles provided further proof for the su...