Synthesis, characterization, drug-loading capacity and safety of novel octyl modified serum albumin micelles

A novel albumin derivative octyl modified serum albumin (OSA) which can form a core-shell structure in aqueous media by self-assembling due to core segregation and a combination of intermolecular forces has been synthesized. The chemical structure and physical properties of OSA were characterized by FTIR, H-1 NMR and TG. The degree of substitution (DS) was in the range of 52.4-69.7% and 48.9-65.8% determined by elemental analysis and fluorescamine assay, respectively. With the increase in the DS of octyl group, the critical micelle concentration (CMC) decreased from 30.1 to 14.7 mg/L because of the increasing hydrophobicity. In the light of the hydrophobic core as a microreservoir for poorly water-soluble drugs, paclitaxel (M) was successfully loaded into OSA micelles by the dialysis method with a high drug-loading (33.1 wt%) and entrapment efficiency (90.5%) due to the synergistic effect of micellar encapsulation and binding interaction between drug and OSA. Compared with PTX-loaded unmodified BSA preparation, PTX-loaded OSA micelles are characterized by small size, narrow size distribution, great drug-loading capacity and enhanced stability. The size of M-loaded micelles was in the range of 123.3-152.8 nm and smaller than their corresponding blank micelles. Hemolysis and cytotoxicity studies showed that OSA was safer than Tween-80 and Cremophor EL as an injectable pharmaceutic adjuvant for M. In terms of the greater drug-loading capacity and safer character, the novel albumin derivative OSA is a prospective injectable delivery system for M. (C) 2009 Elsevier B.V. All rights reserved.