CHARACTERIZATION OF PHYSICAL ENTRAPMENT AND CHEMICAL CONJUGATION OF ADRIAMYCIN IN POLYMERIC MICELLES AND THEIR DESIGN FOR IN-VIVO DELIVERY TO A SOLID TUMOR

An anticancer drug adriamycin (ADR) was incorporated into polymeric mi celles forming from poly(ethylene glycol)poly(aspartic acid) block cop olymer by chemical conjugation and physical entrapment. Structural sta bility of the polymeric micelles was found to be dependent on both the contents of chemically conjugated and physically entrapped ADR. The p olymeric micelle with high contents of the chemically conjugated ADR a nd the physically entrapped ADR expressed very high in vivo antitumor activity against murine C 26 tumor, while the polymeric micelle with o nly the chemically conjugated ADR showed negligible in vivo activity. This indicates that the physically entrapped ADR played a major role i n antitumor activity in vivo. For the polymeric micelle with the high ADR contents, it was found that a dimer of adriamycin molecules formed and that this dimer was physically entrapped in the inner core of the micelle as well as intact ADR. (C) 1998 Elsevier Science B.V.