BIODISTRIBUTION OF MICELLE-FORMING POLYMER DRUG CONJUGATES

Polymeric micelles have potential utility as drug carriers. To this en d, polymeric micelles based on AB block copolymers of polyethylene oxi de (PEO) and poly(aspartic acid) [p(Asp)] with covalently bound Adriam ycin (ADR) were prepared. The micelle forming polymer-drug conjugates [PEO-p(Asp(ADR)] were radiolabeled and their biodistribution was inves tigated after intravenous injection in mice. Long circulation times in blood for some compositions of PEO-p[Asp(ADR)] conjugates were eviden t, which are usually atypical of colloidal drug carriers. This was att ributed to the low interaction of the PEO corona region of the micelle s with biocomponents (e.g., proteins, cells). Low uptake of the PEO-p( Asp(ADR)] conjugates in the liver and spleen was determined. The biodi stribution of the PEO-p[Asp(ADR)] conjugates was apparently dependent on micelle stability; stable micelles could maintain circulation in bl ood, while unstable micelles readily formed free polymer chains which rapidly underwent renal excretion. Long circulation times in blood of PEO-p(Asp(ADR)] conjugates are thought to be prerequisite for enhanced uptake at target sites (e.g., tumors).