Process design for efficient and controlled drug incorporation into polymeric micelle carrier systems

For the efficient and well-controlled incorporation of the anti cancer drug adriamycin (ADR) into the inner core of a thermo-responsive polymeric micelle carrier system, we have analyzed and optimized the incorporation procedure in this paper. A dialysis method was used for preparing the micelle solution and ADR incorporation simultaneously. Quantities of ADR and triethylamine (TEA) were varied and the effects of their quantities were analyzed. Solvent composition at the starting time of dialysis was also varied. The initial dialysis condition, solvent with 40% water, brought about the largest amount and yield of ADR incorporation. With the initial 40% water content, it was considered that the block polymers formed a micelle-like association with a swollen hydrophobic core. This swollen core may be suitable for a large amount of ADR incorporation, since this core, swollen by an organic solvent-water mixture, is expected to show a liquid-state character to allow ADR molecules entry into the cores. By starting the dialysis procedure at this 40% water content, this swollen core suitable for the ADR incorporation is considered to be maintained for a much longer period than a case starting with a polyrner-ADR solution in a solvent with a water content of less than 40%, and, therefore, ADR is expected to be incorporated efficiently. Preparation temperature of 20-25degreesC was found to provide the most effective ADR incorporation in this thermo-responsive polymeric micelle system. These results indicate that the efficient incorporation of ADR can be achieved in consideration of the dynamic micelle formation and drug incorporation processes. (C) 2002 Elsevier Science B.V. All rights reserved.