Annual Report of Cosmetology vol.2, 1994
Synopsis of Original Research Paper

Design of Polymeric Micelles for Novel Carriers inDrug Delivery Systems
Kazunori Kataoka
Research Institure for Biosciences, Science University of Tokyo

Supramolecular structures, such as lipoproteins and viruses, occur in vivo as natural carnersystems. In mimicking such vehicles, we have been studying micelle-forming polymericdrugs as a novel type of drug carrier. Polymeric micelles based on AB block copolymersof polyethylene oxide (PEO) and poly-β-benzyl-L-aspartate (PBLA) were prepared. Suchpolymeric micelles are expected to physically incorporate drugs. AB block copolymers
were synthesized using amino-terminated PEO to initiate the polymerization of β-benzylL-aspartate-N-carboxyanhydride (BLANCA). The composition and molecular weights ofthe block copolymers were established by 1H-NMR. Micellar solutions of PEO-PBLA block
copolymer were characterized by dynamic light scattering. Fluorescence probe techniques
were used to study the polymeric micelles. From changes in the fluorescent intensity and shifts
in the excitation spectrum of pyrene upon micellization, critical micelle concentrations (CMC)of PEO-PBLA block copolymers were obtained. The vibrational structure of monomer pyrene
fluorescence was altered in PEO-PBLA micellar solutions consistent with low polarity within
the PBLA core. In PEO-PBLA micellar solutions, 1,3- (1,1'dipyrenyl)-propane intramolecular
eximer emission, relative to monomer emission was very small ; this indicated very low
mobility of PBLA segments within the micellar core. Further evidence for the limited motionof PBLA segments in the micellar core was obtained by 1H NMR. This limited motion of thePBLA segments in the micellar core is in contrast to low molecular weight surfactants which
commonly show a higher degree of motion within their cores. The ability of PEO-PBLA
micelles to solubilize hydrophobic molecules was studies by UV and fluorescence spectroscopyusing pyrene. Enhanced solubility of pyrene was determined with increasing concentrationsof PEO-PBLA. Then, potential of entrapping Adriamycin (ADR) within micelles based on
PEO-PBLA block copolymers was investigated. The loading process involved bringing ADRand PEO-PBLA into an aqueous milieu from N,N-dimethylformamide (DMF) through asimple dialysis procedure. Evidence for the physical entrapment of ADR within the micelles
was derived from fluorescence spectroscopy, where considerable quenching of fluorescence
was observed for ADR associated with the micelles. In addition, quenching experiments,using a water-soluble quencher (iodide (I−)), showed that the fluorescence of ADR, present inmicellar solutions, was largely uneffected by I−, whereas the fluorescence of free ADR wasreadily quenched. As a result of the entrapment of ADR within the polymeric micelles, thedrug slightly binds serum albumin as evidenced by gel permeation chromatography (GPC). Incontrast, free ADR readily binds serum albumin in aqueous solutions. The finding suggests that
ADR is stably entrapped within PEO-PBLA micelles. The ADR imbued within the micelles isexpected to display markedly dissimilar pharmacokinetics relative to free ADR.

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